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Consanguinity as a Risk Factor for Autism

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Title: Consanguinity as a Risk Factor for Autism
Language: English
Authors: Fouad A. Alshaban, Mohammad Aldosari, Iman Ghazal, Hawraa Al-Shammari, Saba ElHag, I. Richard Thompson, Jennifer Bruder, Hibah Shaath, Fatema Al-Faraj, Mohamed Tolefat, Assal Nasir, Eric Fombonne (ORCID 0000-0002-8605-3538)
Source: Journal of Autism and Developmental Disorders. 2025 55(6):1945-1952.
Availability: Springer. Available from: Springer Nature. One New York Plaza, Suite 4600, New York, NY 10004. Tel: 800-777-4643; Tel: 212-460-1500; Fax: 212-460-1700; e-mail: customerservice@springernature.com; Web site: https://link.springer.com/
Peer Reviewed: Y
Page Count: 8
Publication Date: 2025
Document Type: Journal Articles
Reports - Research
Descriptors: Risk, Symptoms (Individual Disorders), Autism Spectrum Disorders, Environmental Influences, Genetic Disorders, Genetics, Family Influence, Children, Foreign Countries, Family Relationship
Geographic Terms: Qatar
DOI: 10.1007/s10803-023-06137-w
ISSN: 0162-3257
1573-3432
Abstract: Purpose: Genetic and environmental risk factors associated with Autism Spectrum Disorders (ASD) continue to be a focus of research worldwide. Consanguinity, the cultural practice of marrying within a family, is common in cultures and societies of the Middle East, North Africa and parts of Asia. Consanguinity has been investigated as a risk factor for ASD in a limited number of studies, with mixed results. We employed registry and survey data from Qatar to evaluate the role of consanguinity as a risk factor for ASD. Methods: Data were sourced from a national registry and a population-based survey of autism recently conducted in Qatar. We selected a sample of 891 children (mean age: 8.3 years) with (N = 361) or without (N = 530) ASD. Data on consanguinity and covariates were collected through questionnaires and interviews. Results: The prevalence of consanguinity in the overall sample was 41.2% with no significant difference between cases and controls (42.1% vs 41.3%; p = 0.836). In adjusted multiple logistic regression analyses, consanguinity was not associated with risk of ASD (aOR = 1.065; 95% CI: 0.751-1.509; NS). Conclusion: Parental consanguinity was not associated with autism risk in our study. Replication in other populations with high rates of consanguineous unions is recommended.
Abstractor: As Provided
Entry Date: 2025
Accession Number: EJ1470948
Database: ERIC
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  Value: <anid>AN0185099700;aut01jun.25;2025May14.02:48;v2.2.500</anid> <title id="AN0185099700-1">Consanguinity as a Risk Factor for Autism </title> <p>Purpose: Genetic and environmental risk factors associated with Autism Spectrum Disorders (ASD) continue to be a focus of research worldwide. Consanguinity, the cultural practice of marrying within a family, is common in cultures and societies of the Middle East, North Africa and parts of Asia. Consanguinity has been investigated as a risk factor for ASD in a limited number of studies, with mixed results. We employed registry and survey data from Qatar to evaluate the role of consanguinity as a risk factor for ASD. Methods: Data were sourced from a national registry and a population-based survey of autism recently conducted in Qatar. We selected a sample of 891 children (mean age: 8.3 years) with (N = 361) or without (N = 530) ASD. Data on consanguinity and covariates were collected through questionnaires and interviews. Results: The prevalence of consanguinity in the overall sample was 41.2% with no significant difference between cases and controls (42.1% vs 41.3%; p =.836). In adjusted multiple logistic regression analyses, consanguinity was not associated with risk of ASD (aOR = 1.065; 95% CI:.751-1.509; NS). Conclusion: Parental consanguinity was not associated with autism risk in our study. Replication in other populations with high rates of consanguineous unions is recommended.</p> <p>Keywords: ASD; Autism; Consanguinity; Parental age; Risk factor; Sex; Medical and Health Sciences Public Health and Health Services</p> <p>ASD is characterized by pervasive impairments in social reciprocity, communication, stereotyped behaviors, and restricted interests (American Psychiatric Association, [<reflink idref="bib9" id="ref1">9</reflink>]). Studies in Asia, Europe, and North America show prevalence estimates of ASD ranging from 0.7 to 2.8% (Zeidan et al., [<reflink idref="bib42" id="ref2">42</reflink>]; Fombonne et al., [<reflink idref="bib19" id="ref3">19</reflink>]; Maenner et al., [<reflink idref="bib29" id="ref4">29</reflink>]) and a high societal impact (Solmi et al., [<reflink idref="bib39" id="ref5">39</reflink>]). In Qatar, the prevalence rate of ASD was reported at 1.14%, which is in line with global estimates (Alshaban et al., [<reflink idref="bib8" id="ref6">8</reflink>]).</p> <p>Investigations of the contributing genetics toward ASD suggest a complex etiology that varies individually and across chromosome regions (Willsey et al., [<reflink idref="bib41" id="ref7">41</reflink>]). Amongst other risk factors are advanced paternal and maternal age (Al-Mamari et al., [<reflink idref="bib4" id="ref8">4</reflink>]), family history of psychiatric disorders, birth complications and prematurity, prenatal exposure to specific drugs such as valproic acid, and maternal immune system activation occurring through infections, maternal obesity or maternal auto-immune disorder. However, the underlying mechanisms are still a matter of investigation (Modabbernia et al., [<reflink idref="bib34" id="ref9">34</reflink>]).</p> <p>Consanguinity, the practice of marriage between related individuals who share a common ancestor, is a cultural practice that may also influence ASD risk. Consanguineous unions are categorized by the level of consanguinity, typically <emph>first degree</emph> (e.g. first cousin marriages) and <emph>second degree</emph> relations (second cousin and less than second cousin marriages). Consanguinity rates differ in relation to religious, racial, ethnic, and socio-cultural factors. These marriages are common throughout the world, especially in North Africa, the Middle East and West Asia where one billion of the world's population live in communities where consanguinity is common. Intra-familial unions collectively account for 20–50% of the marriages within these communities with substantial area differences (Hamamy et al., [<reflink idref="bib22" id="ref10">22</reflink>]; Tadmouri et al., [<reflink idref="bib40" id="ref11">40</reflink>]; Roy et al., [<reflink idref="bib37" id="ref12">37</reflink>]).</p> <p>Consanguineous marriages increase the risk of the same gene alleles (homozygosity) being passed down from a common ancestor and therefore the presentation of recessive traits in the offspring (Modell & Darr, [<reflink idref="bib35" id="ref13">35</reflink>]; Ben-Omran et al., [<reflink idref="bib10" id="ref14">10</reflink>]). In non-consanguineous unions, these same recessive traits normally go undetected due to heterogeneity and increased recombination options in the gene pool of two unrelated individuals (Hamamy et al., [<reflink idref="bib22" id="ref15">22</reflink>]). Children of consanguineous unions are more likely to present with congenital abnormalities, physical handicaps, inborn errors of metabolism, primary immunodeficiency diseases, and below average overall developmental milestones (specifically developmental delays and intellectual disabilities) (Afzal et al., [<reflink idref="bib1" id="ref16">1</reflink>]; Bener et al., [<reflink idref="bib13" id="ref17">13</reflink>]; Bener & Hussain, [<reflink idref="bib12" id="ref18">12</reflink>]; Bundey & Alam, [<reflink idref="bib16" id="ref19">16</reflink>]; Ehlayel et al., [<reflink idref="bib18" id="ref20">18</reflink>]; Mete et al., [<reflink idref="bib33" id="ref21">33</reflink>]; Masri et al., [<reflink idref="bib32" id="ref22">32</reflink>]; Al-Kandari & Crews, [<reflink idref="bib2" id="ref23">2</reflink>]; Kanaan et al., [<reflink idref="bib24" id="ref24">24</reflink>]; Lakhan et al., [<reflink idref="bib25" id="ref25">25</reflink>]; Roy et al., [<reflink idref="bib37" id="ref26">37</reflink>]).</p> <p>Several studies have explored the relationship between consanguinity and ASD. In one of the first study to report on this association, Eapen et al. ([<reflink idref="bib17" id="ref27">17</reflink>]) analyzed data from a two-stage prevalence survey of autism conducted in a sample of 694 three-year old children from the United Arab Emirates and found no association between ASD and consanguinity. A case-control study conducted in India (Mamidala et al., [<reflink idref="bib31" id="ref28">31</reflink>]) compared 500 cases of ASD to 500 age- and sex-matched controls and reported significant differences in the prevalence of consanguinity across groups (20% vs. 7.2%; ORadj = 3.20; 95% CI: 2.15–4.82, <emph>P</emph> <.001). The estimate was adjusted for the presence of a limited set of confounding variables such as obstetric complications and parental age. The study relied on questionnaires for data collection, no participation rate was provided and selection bias and the representativeness of the study sample were difficult to evaluate.</p> <p>In another case-control study conducted in Lebanon, Hamadé et al. ([<reflink idref="bib21" id="ref29">21</reflink>]) compared 86 children with ASD recruited in specialized schools to 172 age-matched community controls. Consanguinity was reported in 12.8% of the cases and 9.9% of the controls, a non significant difference (<emph>P</emph> =.48). Limitations of the study were the clinical nature of the sample, the lack of details about participation rate; in addition, the study may have under-represented exposure to consanguinity as the authors reported a known prevalence of consanguinity of 35% in Lebanon, a figure much higher than that obtained in the study sample. Bitar et al. ([<reflink idref="bib14" id="ref30">14</reflink>]) conducted a pilot study comparing 64 Lebanese ASD patients and 67 age matched controls. Consanguinity was higher in cases than in controls (25% vs. 10.4%; <emph>P</emph> =.029) and was associated to increased odds of ASD in multiple logistic regression (OR = 4.02; 95% CI: 1.34–12.04). However, there were obvious selections biases in this study; most ASD cases had intellectual disability, 32.8% were deaf, major socio-demographic differences existed between the two groups, and the prevalence of consanguinity among controls was underestimated. The study findings are therefore unreliable. In another Lebanese case-control study of children aged 2 to 18 years, Guisso et al. ([<reflink idref="bib20" id="ref31">20</reflink>]) compared 136 cases to 178 controls to identify risk factors associated with ASD status. In their sample, parental consanguinity was more frequent in the ASD than in the control group (59.4% vs. 40.6%), a difference that fell short of statistical significance (OR = 2.1; 95% CI: 0.98–4.3; <emph>P</emph> =.054). In a subsequent multivariate analysis, consanguinity was marginally predictive of ASD (OR = 2.5; 95% CI: 1.0-2.5) when adjusting on 6 covariates. The study excluded ASD children with milder phenotypes (PDD-NOS, Asperger) and children with any neurodevelopmental disorder were excluded from the controls, raising concerns about sampling bias in that investigation.</p> <p>In Muscat, Oman, whole exome sequencing (WES) results of a review of 97 children aged 1.5–14 years with severe autism documented parental consanguinity in 73.2% of the cases, a higher figure than the 52% population estimate. However, consanguinity was not associated with positive results on WES either in isolation (<emph>P</emph> =.94) or in a multivariate analysis (<emph>P</emph> =.737) (Al-Mamari et al., [<reflink idref="bib5" id="ref32">5</reflink>]). Likewise, in a separate Omani study of 100 children with ASD of whom 31% had consanguineous parents, consanguinity status was not associated with the presence or absence of copy number variants in chromosomal microarrays (Al-Mamari et al., [<reflink idref="bib3" id="ref33">3</reflink>]). In Saudi Arabia, Oommen et al. ([<reflink idref="bib36" id="ref34">36</reflink>]) reported an increased frequency of consanguinity in 100 ASD cases aged 3 to 10 and diagnosed with DSM 5 when compared to 100 controls (52% vs. 37%; unadjusted OR = 1.84, 95% CI:1.05–3.24, <emph>P</emph> =.033 (calculated by us). Risk estimates were adjusted on covariates but presentation of statistical results was unreliable. This study had excluded children with comorbid conditions that could be associated with consanguinity (deafness, metabolic disorders, congenital malformations), relied on parental questionnaires, underestimated the prevalence of consanguinity among controls, making its findings difficult to interpret.</p> <p>In Hong-Kong, Siong et al. ([<reflink idref="bib38" id="ref35">38</reflink>]) compared the developmental and health outcomes of offspring born to 344 consanguineous parents (mostly from Pakistani ethnicity) to 344 controls. The prevalence and effects of parental consanguinity were evaluated. Children from consanguineous unions had a higher likelihood of congenital abnormalities, neonatal death, autosomal recessive disorders and developmental delays. Authors reported a significantly higher prevalence of ASD in the consanguineous group compared to controls (2.1% vs. 0%; <emph>P</emph> =.008). However, the study was based on 7 ASD cases and the nil prevalence among controls suggested sampling bias contributed to this finding. In a study comparing Arab and Jewish sectors in Israel, the clinical profiles of ASD was shown to be more severe among 71 Arab children compared to 129 Israeli peers (Mahajnah et al., [<reflink idref="bib30" id="ref36">30</reflink>]). As expected, consanguinity was reported in 21.1% of the Arab group and 2.3% of the Jewish group (<emph>P</emph> <.0001). As there were no ethnicity-matched controls for either group, the association of consanguinity with ASD status could not be examined. Furthermore, authors estimated the prevalence of ASD in the Jewish and Arab populations to be similar across groups (respectively, 0.43% and 0.38%). The study does not provide evidence of an association of consanguinity with ASD. Finally, in a small investigation of 33 children with ASD recruited among immigrants in Sweden, Linnsand et al. ([<reflink idref="bib27" id="ref37">27</reflink>]) reported a rate of consanguinity of 9.7%; however, the absence of controls drawn from the same populations made the findings difficult to interpret.</p> <p>Although they were not designed to assess consanguinity as a risk factor for ASD, two studies have examined the relationship between consanguinity and the severity of the autism phenotype within ASD samples. In the prevalence study in the State of Qatar, about 45% of participants with ASD came from consanguineous families. In analyses restricted to the pool of participants with ASD, consanguinity was a statistically significant predictor for ASD severity after controlling for several covariates (Alshaban et al., [<reflink idref="bib8" id="ref38">8</reflink>]). By contrast, consanguinity was not significantly correlated with ASD severity in a study of a small sample in Saudi Arabia (Aldera et al., [<reflink idref="bib6" id="ref39">6</reflink>]).</p> <p>Overall, the results of existing studies are mixed and inconclusive. Most investigations suffered from serious methodological limitations that include reliance on small samples of convenience, use of exclusion criteria that jeopardized the representativeness of both cases and controls groups, limited evaluation of associated risk factors that could confound the association between consanguinity and ASD, or absence of control group altogether.</p> <p>In the present study, we used a case-control design to examine rates of consanguinity in the ASD population compared to controls using a large representative sample of participants from Qatar. If consanguinity is a risk factor for ASD, we should find a significantly higher prevalence of consanguinity in the ASD sample than in the control sample. Furthermore, the odds of ASD should remain significantly raised even after controlling for variables that could confound the association between consanguinity and ASD.</p> <hd id="AN0185099700-2">Methods</hd> <p></p> <hd id="AN0185099700-3">Setting</hd> <p>Qatar is a small, and highly urbanized peninsular state in the Gulf region. Education is mandatory and literacy and poverty are not of concern for Qatar's local population. Qatari nationals are ethnically and regionally homogeneous and share common beliefs and traditions with other Gulf countries. Unlike many countries where consanguinity has been declining with increasing education and urbanization, the opposite trend has been noted in Qatar and Qatar's current rate of consanguinity is 54%, comprised primarily of first-cousin marriages (Bener & Alali, [<reflink idref="bib11" id="ref40">11</reflink>]). Rates of consanguinity are similar in other Gulf Cooperation Council (GCC) countries (Kuwait, Saudi Arabia, Bahrain, United Arab Emirates and Oman). In the present study, we build on the data from our population-based autism survey (Alshaban et al., [<reflink idref="bib8" id="ref41">8</reflink>]) and from the ASD Registry of Qatar to compare the rates of parental consanguinity in participants with or without ASD living in the State of Qatar to further elucidate whether consanguinity is a risk factor for ASD.</p> <hd id="AN0185099700-4">Participants</hd> <p>Participants were recruited from two sources: (<reflink idref="bib1" id="ref42">1</reflink>) a population survey recently conducted in the whole country, and (<reflink idref="bib2" id="ref43">2</reflink>) a national registry for ASD.</p> <p> <emph>1. Autism survey</emph>: children aged 5 to 12 whose parents held a valid residence permit in Qatar and attending one of 93 schools participating in the survey were included in the first screening phase. Participants were screened using the Arabic version of the Social Communications Questionnaires (SCQ) previously validated in an Arabic sample (Aldosari et al., [<reflink idref="bib7" id="ref44">7</reflink>]). Participants who scored above the threshold were invited to participate to the second survey phase of diagnostic confirmation. In addition, children already diagnosed with ASD or suspected to have ASD were selected from Qatar's main clinical centers: Shafallah Center for Children with Disabilities, the Child Development Center, Rumailah Hospital, Hamad Medical Corporation, and private specialized centers (Hope Center, Step by Step Center, and Al Tamakkun School) and were invited to the phase of diagnostic confirmation. In the second phase, a detailed in-person assessment of the child with standardized diagnostic tools (see below) was performed. When in-person assessments were not possible, a detailed medical and school record review was performed. In all instances, final diagnosis was confirmed by expert clinical judgement using DSM 5 criteria. In addition, a sample of children who screened negative on the SCQ in the first phase was investigated further with a detailed parental interview to evaluate the false negative rate in the screening phase. Participants who were confirmed to not have ASD served as controls for the present investigation. Further details about the survey are available elsewhere (Alshaban et al., [<reflink idref="bib8" id="ref45">8</reflink>]).</p> <p>2. <emph>ASD registry</emph>: The ASD registry was established in 2012 and all children and adults diagnosed with ASD in any clinical center have been invited to join it. Children in the same age group who were in the registry but not survey participants were also selected for this study.</p> <p> <emph>3. Selection procedures</emph>: Inclusion criteria for the current study were: (a) a confirmed diagnosis of ASD in the registry or the survey; (b) an age between 5 and 12, and; (c) family was from Qatar or a GCC country. Potential participants from other Middle East, Arabic, Asian or other countries were not included as the rates of consanguinity in their populations are known to be different than those from the GCC countries, and controls from non-GCC countries were not available.</p> <p>Of the 969 participants whose parents were from Qatar or another GCC country, consanguinity data were missing for 78 subjects, leaving a sample of 891 participants (361 with ASD, 530 controls) for this analysis.</p> <hd id="AN0185099700-5">Measures and Data</hd> <p></p> <hd id="AN0185099700-6">Autism Cases</hd> <p>In the epidemiological survey, all participants were first screened with the Arabic version of the SCQ (Aldosari et al., [<reflink idref="bib7" id="ref46">7</reflink>]) as explained above. In the second phase of diagnostic confirmation, in-person diagnostic evaluations relied on the administration of the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2; Lord et al., [<reflink idref="bib28" id="ref47">28</reflink>]), on a developmental and family history obtained through parental interview, a review of existing medical and school records, and direct clinical examination. All research team members were trained and certified in administering and scoring ADOS-2. The final ASD diagnosis according to the Diagnostic and Statistical Manual of mental disorders (5th ed.) (DSM-5; American Psychiatric Association, [<reflink idref="bib9" id="ref48">9</reflink>]) was confirmed after review of all available data by experienced clinicians. Similar procedures were employed for diagnostic confirmation of all registry participants.</p> <hd id="AN0185099700-7">Controls</hd> <p>they were recruited from participants to the epidemiological survey among children attending normal schools across Qatar who scored negatively on the SCQ. Parents participated in a follow-up telephone interview to collect developmental, medical, and behavioral information allowing to confirm the absence of ASD; no other exclusion criterion was employed (see details in Alshaban et al., [<reflink idref="bib8" id="ref49">8</reflink>]).</p> <hd id="AN0185099700-8">Consanguinity Information</hd> <p>for all ASD and control participants, it was collected through parental phone interviews and questionnaires at the time of inclusion in the Registry or of survey participation, supplemented by record review. Consanguinity was considered present only in first-degree (first cousin marriages) and second-degree (second or third cousin marriages) instances.</p> <hd id="AN0185099700-9">Other Data</hd> <p>a questionnaire completed by parents from all participants included socio-demographic data (index child's age and sex, mother and father's education, paternal and maternal age, number of children, affected status of siblings and other relatives) and a medical questionnaire was completed by the research team or the referent clinician that provided data on birth circumstances (birth weight, prematurity), comorbid conditions (epilepsy, aggressive behaviors, ADHD, anxiety symptoms, sleep disorders) and developmental features (history of language delay, current language level, regression, intellectual disability).</p> <hd id="AN0185099700-10">Missing Data</hd> <p>For incomplete records, the research team contacted the families to supplement the missing information whenever possible. Maternal education was missing in 61.4% of subjects whereas father's education was missing in only 1.2%. Father's and mother's education variables were highly correlated when they were both available (Spearman r =.533; p <.001). Accordingly, we used father's education as an index of parental education and socio-economic position.</p> <hd id="AN0185099700-11">Statistical Analyses</hd> <p>Data were analyzed with the Statistical Package for the Social Sciences (IBM SPSS, [<reflink idref="bib23" id="ref50">23</reflink>]). Chi-square and Fisher's exact tests were used to compare participants with or without parental consanguinity for categorical variables. Student t-tests were used for normally distributed continuous variables. To evaluate the association between autism and parental consanguinity, we employed first binary logistic regression with ASD status as a binary outcome and parental consanguinity as a binary predictor. Next, we examined clinical and socio-demographic variable distributions in consanguineous and non-consanguineous families to identify those variables that could be confounding the consanguinity-autism association. Potential confounders were selected based on their statistical association with consanguinity (using a p-value of p <.15) and on prior knowledge from the autism literature. Multivariate logistic regression was then performed with the set of potential confounders added as predictors to the logistic model. Hosmer-Lemeshow statistic was used to assess the model fit. Participants with missing data were excluded from analyses; no imputation technique was used. Throughout, a p-value of 0.05 was set as the a priori threshold for statistical significance.</p> <hd id="AN0185099700-12">Ethical Approval</hd> <p>This study was approved by the Qatar Biomedical Research Institute Institutional Review Board (IRB) research ethics committee.</p> <hd id="AN0185099700-13">Results</hd> <p>The majority (92.8%) of the sample was Qatari with no difference between country of origin (Qatar vs. other GCC) and case-control status (Fisher's exact test; <emph>P</emph> =.188). Mean age was 8.28 years (SD = 2.70) and there were 56.2% males with a statistically significant difference by group (ASD: 84.8%; controls: 36.8%; Fisher's exact test: <emph>P</emph><.001). Consanguinity was reported in 41.6% of the sample (ASD group: 42.1%; controls: 41.3%). Although consanguinity was higher in the Other GCC subsample, the difference did not reach statistical significance (Qatar: 40.7%; Other GCC: 53.1%; <emph>P</emph> =.065).</p> <p>We then examined which variables were associated with consanguinity (Table 1). Variables with > 20% missing data were excluded (birth weight; prematurity; regression; number of siblings; recurrence of ASD in first- and second-degree relatives; intellectual disability). For socio-demographic characteristics, both mothers and fathers from consanguineous unions were significantly younger than non-consanguineous parents. For clinical variables, there was a trend for children from consanguineous unions to be more often males and to have a lower prevalence of epilepsy. All other variables were not associated with consanguinity status.</p> <p>Table 1 Qatar and GCC sample: sample characteristics by consanguinity status</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left"><p>Sample characteristic</p></th><th align="left" colspan="2"><p>Non consanguineous parents (N = 520)</p></th><th align="left" colspan="2"><p>Consanguineous parents (N = 371)</p></th><th align="left"><p>p-value</p></th></tr><tr><th align="left" /><th align="left"><p><bold>N</bold></p></th><th align="left"><p><bold>%</bold></p></th><th align="left"><p><bold>N</bold></p></th><th align="left"><p><bold>%</bold></p></th><th align="left" /></tr></thead><tbody><tr><td align="left"><p><bold>Child</bold></p></td><td align="left" /><td align="left" /><td align="left" /><td align="left" /><td align="left" /></tr><tr><td align="left"><p>Has ASD</p></td><td align="left"><p>209</p></td><td align="left"><p>40.2</p></td><td align="left"><p>152</p></td><td align="left"><p>41.0</p></td><td align="left"><p>0.836</p></td></tr><tr><td align="left"><p>Male sex</p></td><td align="left"><p>279</p></td><td align="left"><p>53.7</p></td><td align="left"><p>222</p></td><td align="left"><p>59.8</p></td><td align="left"><p>0.075</p></td></tr><tr><td align="left"><p>Language delay</p></td><td align="left"><p>65</p></td><td align="left"><p>12.5</p></td><td align="left"><p>35</p></td><td align="left"><p>9.5</p></td><td align="left"><p>0.163</p></td></tr><tr><td align="left"><p>Nonverbal</p></td><td align="left"><p>24</p></td><td align="left"><p>4.6</p></td><td align="left"><p>17</p></td><td align="left"><p>4.6</p></td><td align="left"><p>1.0</p></td></tr><tr><td align="left"><p>Epilepsy</p></td><td align="left"><p>31</p></td><td align="left"><p>6.3</p></td><td align="left"><p>12</p></td><td align="left"><p>3.4</p></td><td align="left"><p>0.080</p></td></tr><tr><td align="left"><p>Sleep disorder</p></td><td align="left"><p>18</p></td><td align="left"><p>3.5</p></td><td align="left"><p>17</p></td><td align="left"><p>4.6</p></td><td align="left"><p>0.485</p></td></tr><tr><td align="left"><p>ADHD</p></td><td align="left"><p>79</p></td><td align="left"><p>15.7</p></td><td align="left"><p>47</p></td><td align="left"><p>13.1</p></td><td align="left"><p>0.328</p></td></tr><tr><td align="left"><p>Anxiety</p></td><td align="left"><p>29</p></td><td align="left"><p>5.6</p></td><td align="left"><p>14</p></td><td align="left"><p>3.8</p></td><td align="left"><p>0.267</p></td></tr><tr><td align="left"><p>Aggressive behaviors</p></td><td align="left"><p>19</p></td><td align="left"><p>3.7</p></td><td align="left"><p>11</p></td><td align="left"><p>3.0</p></td><td align="left"><p>0.707</p></td></tr><tr><td align="left"><p><bold>Socio-demographic</bold></p></td><td align="left" /><td align="left" /><td align="left" /><td align="left" /><td align="left" /></tr><tr><td align="left"><p>Country</p></td><td align="left" /><td align="left" /><td align="left" /><td align="left" /><td align="left" /></tr><tr><td align="left"><p>• Qatar</p></td><td align="left"><p>490</p></td><td align="left"><p>94.2</p></td><td align="left"><p>337</p></td><td align="left"><p>90.8</p></td><td align="left"><p>0.065</p></td></tr><tr><td align="left"><p>• Other GCC</p></td><td align="left"><p>30</p></td><td align="left"><p>5.8</p></td><td align="left"><p>34</p></td><td align="left"><p>9.2</p></td><td align="left" /></tr><tr><td align="left"><p>Father's education</p></td><td align="left" /><td align="left" /><td align="left" /><td align="left" /><td align="left" /></tr><tr><td align="left"><p>• Primary school or less</p></td><td align="left"><p>26</p></td><td align="left"><p>5.1</p></td><td align="left"><p>26</p></td><td align="left"><p>7.2</p></td><td align="left" /></tr><tr><td align="left"><p>• Secondary school</p></td><td align="left"><p>207</p></td><td align="left"><p>40.5</p></td><td align="left"><p>142</p></td><td align="left"><p>39.1</p></td><td align="left" /></tr><tr><td align="left"><p>• College</p></td><td align="left"><p>218</p></td><td align="left"><p>42.7</p></td><td align="left"><p>160</p></td><td align="left"><p>44.1</p></td><td align="left"><p>0.458</p></td></tr><tr><td align="left"><p>• Master's or PhD</p></td><td align="left"><p>60</p></td><td align="left"><p>11.7</p></td><td align="left"><p>35</p></td><td align="left"><p>9.6</p></td><td align="left" /></tr><tr><td align="left" /><td align="left"><p><bold>Mean</bold></p></td><td align="left"><p><bold>SD</bold></p></td><td align="left"><p><bold>Mean</bold></p></td><td align="left"><p><bold>SD</bold></p></td><td align="left" /></tr><tr><td align="left"><p>Child's age at enrollment</p></td><td align="left"><p>8.29</p></td><td align="left"><p>2.39</p></td><td align="left"><p>8.27</p></td><td align="left"><p>3.07</p></td><td align="left"><p>0.932</p></td></tr><tr><td align="left"><p>Paternal age at birth</p></td><td align="left"><p>34.76</p></td><td align="left"><p>6.81</p></td><td align="left"><p>32.50</p></td><td align="left"><p>7.84</p></td><td align="left"><p>< 0.001</p></td></tr><tr><td align="left"><p>Maternal age at birth</p></td><td align="left"><p>30.18</p></td><td align="left"><p>6.03</p></td><td align="left"><p>28.59</p></td><td align="left"><p>6.26</p></td><td align="left"><p>< 0.001</p></td></tr></tbody></table> </ephtml> </p> <p>Using an <emph>a priori</emph> criterion of <emph>P</emph> =.15 selected four covariates (paternal age, maternal age, child male sex, child epilepsy); because they have also been associated with ASD in previous studies, all four variables were selected as potential confounders for the multivariate logistic model (Table 2). In unadjusted logistic regression, consanguinity was not associated with autism (OR = 1.079; 95%:.802-1.451; NS). After adjustment of the four covariates, consanguinity remained not statistically predictive of autism (OR = 1.065; 95%: 0.751-1.509; NS). In the multivariate model, child sex (p <.001), epilepsy (p <.001) and maternal age (p =.023) were significant predictors; after adjustment on maternal age, paternal age was no longer a significant predictor (<emph>P</emph>=.70). The fit of the model was satisfactory (Hosmer-Lemeshow chi-square = 10.96; df = 8; <emph>P</emph> =.20).</p> <p>Table 2 Association between ASD and consanguinity (logistic regression models)</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left" /><th align="left"><p>β</p></th><th align="left"><p>S.E.</p></th><th align="left"><p>Odds-ratio</p></th><th align="left"><p>95% Confidence interval</p></th><th align="left"><p>p-value</p></th></tr></thead><tbody><tr><td align="left"><p><bold>Crude</bold></p></td><td align="left" /><td align="left" /><td align="left" /><td align="left" /><td align="left" /></tr><tr><td align="left"><p>Consanguinity</p></td><td align="left"><p>0.076</p></td><td align="left"><p>0.151</p></td><td char="." align="char"><p>1.079</p></td><td char="?" align="char"><p>0.802-1.451</p></td><td align="left"><p>0.615</p></td></tr><tr><td align="left"><p><bold>Adjusted</bold><sup><bold>a</bold></sup></p></td><td align="left" /><td align="left" /><td align="left" /><td align="left" /><td align="left" /></tr><tr><td align="left"><p>Consanguinity</p></td><td align="left"><p>0.063</p></td><td align="left"><p>0.178</p></td><td char="." align="char"><p>1.065</p></td><td char="?" align="char"><p>0.751-1.509</p></td><td align="left"><p>0.725</p></td></tr></tbody></table> </ephtml> </p> <p>a: model adjusted on child sex, child epilepsy (present/absent), paternal and maternal age (as continuous variables)</p> <p>To test for possible heterogeneity of effects between the Qatar and the GCC subsamples, the model was recalculated after excluding the GCC participants. After restricting the model to Qatar participants only, consanguinity remained not significantly associated with autism in the multivariate analysis (aOR = 1.14; 95%CI: 0.795-1.648; <emph>P</emph> =.468).</p> <hd id="AN0185099700-14">Discussion</hd> <p>This study did not find that consanguinity is a risk factor for ASD. Our negative results are consistent with those of Eapen et al. ([<reflink idref="bib17" id="ref51">17</reflink>]) who found no association between consanguinity and ASD in a sample from the UAE, a Gulf state that is ethnically, genetically, culturally, socially, and geographically similar to Qatar. Taken together, the findings provide no evidence to support consanguinity as a risk factor for ASD in the Gulf countries. They are also consistent with some previous studies carried out in other non-GCC populations (e.g. Hamadé et al., [<reflink idref="bib21" id="ref52">21</reflink>]), which found no association of consanguinity with ASD status. By contrast, other investigations reported an association between parental consanguinity and offspring autism risk in studies with variable methodologies and different ethnic populations (Oommen et al., [<reflink idref="bib36" id="ref53">36</reflink>]; Guisso et al., [<reflink idref="bib20" id="ref54">20</reflink>]; Mamidala et al., [<reflink idref="bib31" id="ref55">31</reflink>]). However, in these studies, other risk factors related independently to both ASD and consanguinity, were not adjusted for and could have confounded the reported association; in addition, these investigations derived from clinical rather than population-based samples, with likely bias in selecting cases and controls samples.</p> <p>The prevalence of consanguinity in our sample was in line with current estimates of consanguinity in the Qatar and GCC population, with a small observed difference (+ 0.8%) in rates of consanguinity between cases and controls. With a consanguinity prevalence of 41.3% among controls, our study was powered to detect a difference of 6.6% or more between the groups. Thus, the lack of association found in our study did not reflect insufficient statistical power. In addition, we could adjust the estimate on known risk factors that were also confounding factors in our data, such as sex of the index child and advanced parental age. Cases and controls were assessed with standardized tools and clinical judgement making misclassification on case status very unlikely. Non-differential misclassification of exposure (e.g. consanguinity) could have biased the results towards the null but is unlikely since consanguinity was reported at a rate consistent with population estimates.</p> <p>A significant association between parental consanguinity and ASD severity was previously reported in a national prevalence study in Qatar (Alshaban et al., [<reflink idref="bib8" id="ref56">8</reflink>]). Combined together, our results suggest that consanguinity does not increase the risk of ASD but may be associated with increased severity, a pattern that was documented in other conditions such as Down syndrome (Bittles & Black, [<reflink idref="bib15" id="ref57">15</reflink>]). In a comparison of Jewish and Bedouin-Arab children with ASD, Levaot et al. ([<reflink idref="bib26" id="ref58">26</reflink>]) reported more severe clinical features in the Bedouin-Arab group and observed that the rate of consanguinity in the referred Bedouin sample was significantly higher than that in the underlying Bedouin population (73.3% vs. 44.8%); however, there was no direct comparison between children from consanguineous and non-consanguineous Bedouin families, precluding any definite conclusion to be drawn on the role of consanguinity on ASD severity in this referred sample. In a Saudi Arabia descriptive study of 77 children with ASD (Aldera et al., [<reflink idref="bib6" id="ref59">6</reflink>]), consanguinity was reported in 41.6% of the families; there were no differences in severity between children from consanguineous or non-consanguineous parents, a result that held true after adjustment on several covariates (<emph>P</emph> =.70). Thus, more studies are required to examine further the possible role of consanguinity in modulating the severity of the autism phenotype.</p> <p>Strengths of our study included a large sample size with population-based recruitment, a comprehensive clinical assessment of cases with ASD, and statistical adjustment on confounding variables. Limitations included missing data on variables that could not consequently be adjusted for, and the possibility that unmeasured confounding factors may have biased the estimate of association. In conclusion, our evidence does not support consanguinity as a risk factor for ASD, however further studies are needed to replicate and verify these findings in other consanguineous populations.</p> <hd id="AN0185099700-15">Acknowledgements</hd> <p>We wish to express our appreciation to the families and their children for their time and participation. The authors thank all collaborating centers and institutes for their support and participation in this study.</p> <hd id="AN0185099700-16">Funding</hd> <p>This study was funded by the Qatar National Research Fund (QNRF) and Qatar Biomedical Research Institute (QBRI).</p> <hd id="AN0185099700-17">Declarations</hd> <p></p> <hd id="AN0185099700-18">Competing interests</hd> <p>All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.</p> <hd id="AN0185099700-19">Publisher's Note</hd> <p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p> <ref id="AN0185099700-20"> <title> References </title> <blist> <bibl id="bib1" idref="ref16" type="bt">1</bibl> <bibtext> Afzal RM, Lund AM, Skovby F. 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Richard Thompson; Jennifer Bruder; Hibah Shaath; Fatema Al-Faraj; Mohamed Tolefat; Assal Nasir and Eric Fombonne</p> <p>Reported by Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author</p> </aug> <nolink nlid="nl1" bibid="bib42" firstref="ref2"></nolink> <nolink nlid="nl2" bibid="bib19" firstref="ref3"></nolink> <nolink nlid="nl3" bibid="bib29" firstref="ref4"></nolink> <nolink nlid="nl4" bibid="bib39" firstref="ref5"></nolink> <nolink nlid="nl5" bibid="bib41" firstref="ref7"></nolink> <nolink nlid="nl6" bibid="bib34" firstref="ref9"></nolink> <nolink nlid="nl7" bibid="bib22" firstref="ref10"></nolink> <nolink nlid="nl8" bibid="bib40" firstref="ref11"></nolink> <nolink nlid="nl9" bibid="bib37" firstref="ref12"></nolink> <nolink nlid="nl10" bibid="bib35" firstref="ref13"></nolink> <nolink nlid="nl11" bibid="bib10" firstref="ref14"></nolink> <nolink nlid="nl12" bibid="bib13" firstref="ref17"></nolink> <nolink nlid="nl13" bibid="bib12" firstref="ref18"></nolink> <nolink nlid="nl14" bibid="bib16" firstref="ref19"></nolink> <nolink nlid="nl15" bibid="bib18" firstref="ref20"></nolink> <nolink nlid="nl16" bibid="bib33" firstref="ref21"></nolink> <nolink nlid="nl17" bibid="bib32" firstref="ref22"></nolink> <nolink nlid="nl18" bibid="bib24" firstref="ref24"></nolink> <nolink nlid="nl19" bibid="bib25" firstref="ref25"></nolink> <nolink nlid="nl20" bibid="bib17" firstref="ref27"></nolink> <nolink nlid="nl21" bibid="bib31" firstref="ref28"></nolink> <nolink nlid="nl22" bibid="bib21" firstref="ref29"></nolink> <nolink nlid="nl23" bibid="bib14" firstref="ref30"></nolink> <nolink nlid="nl24" bibid="bib20" firstref="ref31"></nolink> <nolink nlid="nl25" bibid="bib36" firstref="ref34"></nolink> <nolink nlid="nl26" bibid="bib38" firstref="ref35"></nolink> <nolink nlid="nl27" bibid="bib30" firstref="ref36"></nolink> <nolink nlid="nl28" bibid="bib27" firstref="ref37"></nolink> <nolink nlid="nl29" bibid="bib11" firstref="ref40"></nolink> <nolink nlid="nl30" bibid="bib28" firstref="ref47"></nolink> <nolink nlid="nl31" bibid="bib23" firstref="ref50"></nolink> <nolink nlid="nl32" bibid="bib15" firstref="ref57"></nolink> <nolink nlid="nl33" bibid="bib26" firstref="ref58"></nolink>
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Items – Name: Title
  Label: Title
  Group: Ti
  Data: Consanguinity as a Risk Factor for Autism
– Name: Language
  Label: Language
  Group: Lang
  Data: English
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Fouad+A%2E+Alshaban%22">Fouad A. Alshaban</searchLink><br /><searchLink fieldCode="AR" term="%22Mohammad+Aldosari%22">Mohammad Aldosari</searchLink><br /><searchLink fieldCode="AR" term="%22Iman+Ghazal%22">Iman Ghazal</searchLink><br /><searchLink fieldCode="AR" term="%22Hawraa+Al-Shammari%22">Hawraa Al-Shammari</searchLink><br /><searchLink fieldCode="AR" term="%22Saba+ElHag%22">Saba ElHag</searchLink><br /><searchLink fieldCode="AR" term="%22I%2E+Richard+Thompson%22">I. Richard Thompson</searchLink><br /><searchLink fieldCode="AR" term="%22Jennifer+Bruder%22">Jennifer Bruder</searchLink><br /><searchLink fieldCode="AR" term="%22Hibah+Shaath%22">Hibah Shaath</searchLink><br /><searchLink fieldCode="AR" term="%22Fatema+Al-Faraj%22">Fatema Al-Faraj</searchLink><br /><searchLink fieldCode="AR" term="%22Mohamed+Tolefat%22">Mohamed Tolefat</searchLink><br /><searchLink fieldCode="AR" term="%22Assal+Nasir%22">Assal Nasir</searchLink><br /><searchLink fieldCode="AR" term="%22Eric+Fombonne%22">Eric Fombonne</searchLink> (ORCID <externalLink term="http://orcid.org/0000-0002-8605-3538">0000-0002-8605-3538</externalLink>)
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="SO" term="%22Journal+of+Autism+and+Developmental+Disorders%22"><i>Journal of Autism and Developmental Disorders</i></searchLink>. 2025 55(6):1945-1952.
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  Label: Availability
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  Data: Springer. Available from: Springer Nature. One New York Plaza, Suite 4600, New York, NY 10004. Tel: 800-777-4643; Tel: 212-460-1500; Fax: 212-460-1700; e-mail: customerservice@springernature.com; Web site: https://link.springer.com/
– Name: PeerReviewed
  Label: Peer Reviewed
  Group: SrcInfo
  Data: Y
– Name: Pages
  Label: Page Count
  Group: Src
  Data: 8
– Name: DatePubCY
  Label: Publication Date
  Group: Date
  Data: 2025
– Name: TypeDocument
  Label: Document Type
  Group: TypDoc
  Data: Journal Articles<br />Reports - Research
– Name: Subject
  Label: Descriptors
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Risk%22">Risk</searchLink><br /><searchLink fieldCode="DE" term="%22Symptoms+%28Individual+Disorders%29%22">Symptoms (Individual Disorders)</searchLink><br /><searchLink fieldCode="DE" term="%22Autism+Spectrum+Disorders%22">Autism Spectrum Disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Environmental+Influences%22">Environmental Influences</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+Disorders%22">Genetic Disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Genetics%22">Genetics</searchLink><br /><searchLink fieldCode="DE" term="%22Family+Influence%22">Family Influence</searchLink><br /><searchLink fieldCode="DE" term="%22Children%22">Children</searchLink><br /><searchLink fieldCode="DE" term="%22Foreign+Countries%22">Foreign Countries</searchLink><br /><searchLink fieldCode="DE" term="%22Family+Relationship%22">Family Relationship</searchLink>
– Name: Subject
  Label: Geographic Terms
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Qatar%22">Qatar</searchLink>
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1007/s10803-023-06137-w
– Name: ISSN
  Label: ISSN
  Group: ISSN
  Data: 0162-3257<br />1573-3432
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Purpose: Genetic and environmental risk factors associated with Autism Spectrum Disorders (ASD) continue to be a focus of research worldwide. Consanguinity, the cultural practice of marrying within a family, is common in cultures and societies of the Middle East, North Africa and parts of Asia. Consanguinity has been investigated as a risk factor for ASD in a limited number of studies, with mixed results. We employed registry and survey data from Qatar to evaluate the role of consanguinity as a risk factor for ASD. Methods: Data were sourced from a national registry and a population-based survey of autism recently conducted in Qatar. We selected a sample of 891 children (mean age: 8.3 years) with (N = 361) or without (N = 530) ASD. Data on consanguinity and covariates were collected through questionnaires and interviews. Results: The prevalence of consanguinity in the overall sample was 41.2% with no significant difference between cases and controls (42.1% vs 41.3%; p = 0.836). In adjusted multiple logistic regression analyses, consanguinity was not associated with risk of ASD (aOR = 1.065; 95% CI: 0.751-1.509; NS). Conclusion: Parental consanguinity was not associated with autism risk in our study. Replication in other populations with high rates of consanguineous unions is recommended.
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  Data: As Provided
– Name: DateEntry
  Label: Entry Date
  Group: Date
  Data: 2025
– Name: AN
  Label: Accession Number
  Group: ID
  Data: EJ1470948
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=eric&AN=EJ1470948
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  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1007/s10803-023-06137-w
    Languages:
      – Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 8
        StartPage: 1945
    Subjects:
      – SubjectFull: Risk
        Type: general
      – SubjectFull: Symptoms (Individual Disorders)
        Type: general
      – SubjectFull: Autism Spectrum Disorders
        Type: general
      – SubjectFull: Environmental Influences
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      – SubjectFull: Qatar
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    Titles:
      – TitleFull: Consanguinity as a Risk Factor for Autism
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            – D: 01
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              Type: published
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