Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N = 53 949).
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| Title: | Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N = 53 949). |
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| Authors: | Davies, G., Armstrong, N., Bis, J. C., Bressler, J., Chouraki, V., Giddaluru, S., Hofer, E., Ibrahim-Verbaas, C. A., Kirin, M., Lahti, J., van der Lee, S. J., Hellard, S. Le, Liu, T., Marioni, R. E., Oldmeadow, C., Postmus, I., Smith, A. V., Smith, J. A., Thalamuthu, A., Thomson, R. |
| Source: | Molecular Psychiatry. Feb2015, Vol. 20 Issue 2, p183-192. 10p. |
| Subjects: | Cognitive ability, Multiple correspondence analysis (Statistics), Single nucleotide polymorphisms, Neurobehavioral disorders, Alzheimer's disease |
| Abstract: | General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N = 53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P = 3.93× 10-9, MIR2113; rs l7522122, P = 2.55 × 10-8, AKAP6; rsl 0119, P=5.67 × 10-9, APOE/TOMM40).\Ne report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P= 1 × 10-6). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N= 6617) and the Health and Retirement Study (N= 5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e. = 5%) and 28% (s.e. = 7%), respectively. Using polygenic prediction analysis, -1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N = 5487; P= 1.5 × 10 17). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C. [ABSTRACT FROM AUTHOR] |
| Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 101206649 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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A.</searchLink><br /><searchLink fieldCode="AR" term="%22Kirin%2C+M%2E%22">Kirin, M.</searchLink><br /><searchLink fieldCode="AR" term="%22Lahti%2C+J%2E%22">Lahti, J.</searchLink><br /><searchLink fieldCode="AR" term="%22van+der+Lee%2C+S%2E+J%2E%22">van der Lee, S. J.</searchLink><br /><searchLink fieldCode="AR" term="%22Hellard%2C+S%2E+Le%22">Hellard, S. Le</searchLink><br /><searchLink fieldCode="AR" term="%22Liu%2C+T%2E%22">Liu, T.</searchLink><br /><searchLink fieldCode="AR" term="%22Marioni%2C+R%2E+E%2E%22">Marioni, R. E.</searchLink><br /><searchLink fieldCode="AR" term="%22Oldmeadow%2C+C%2E%22">Oldmeadow, C.</searchLink><br /><searchLink fieldCode="AR" term="%22Postmus%2C+I%2E%22">Postmus, I.</searchLink><br /><searchLink fieldCode="AR" term="%22Smith%2C+A%2E+V%2E%22">Smith, A. V.</searchLink><br /><searchLink fieldCode="AR" term="%22Smith%2C+J%2E+A%2E%22">Smith, J. A.</searchLink><br /><searchLink fieldCode="AR" term="%22Thalamuthu%2C+A%2E%22">Thalamuthu, A.</searchLink><br /><searchLink fieldCode="AR" term="%22Thomson%2C+R%2E%22">Thomson, R.</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Molecular+Psychiatry%22">Molecular Psychiatry</searchLink>. Feb2015, Vol. 20 Issue 2, p183-192. 10p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Cognitive+ability%22">Cognitive ability</searchLink><br /><searchLink fieldCode="DE" term="%22Multiple+correspondence+analysis+%28Statistics%29%22">Multiple correspondence analysis (Statistics)</searchLink><br /><searchLink fieldCode="DE" term="%22Single+nucleotide+polymorphisms%22">Single nucleotide polymorphisms</searchLink><br /><searchLink fieldCode="DE" term="%22Neurobehavioral+disorders%22">Neurobehavioral disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Alzheimer's+disease%22">Alzheimer's disease</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N = 53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P = 3.93× 10-9, MIR2113; rs l7522122, P = 2.55 × 10-8, AKAP6; rsl 0119, P=5.67 × 10-9, APOE/TOMM40).\Ne report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P= 1 × 10-6). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N= 6617) and the Health and Retirement Study (N= 5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e. = 5%) and 28% (s.e. = 7%), respectively. Using polygenic prediction analysis, -1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N = 5487; P= 1.5 × 10 17). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1038/mp.2014.188 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 10 StartPage: 183 Subjects: – SubjectFull: Cognitive ability Type: general – SubjectFull: Multiple correspondence analysis (Statistics) Type: general – SubjectFull: Single nucleotide polymorphisms Type: general – SubjectFull: Neurobehavioral disorders Type: general – SubjectFull: Alzheimer's disease Type: general Titles: – TitleFull: Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N = 53 949). Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Davies, G. – PersonEntity: Name: NameFull: Armstrong, N. – PersonEntity: Name: NameFull: Bis, J. C. – PersonEntity: Name: NameFull: Bressler, J. – PersonEntity: Name: NameFull: Chouraki, V. – PersonEntity: Name: NameFull: Giddaluru, S. – PersonEntity: Name: NameFull: Hofer, E. – PersonEntity: Name: NameFull: Ibrahim-Verbaas, C. A. – PersonEntity: Name: NameFull: Kirin, M. – PersonEntity: Name: NameFull: Lahti, J. – PersonEntity: Name: NameFull: van der Lee, S. J. – PersonEntity: Name: NameFull: Hellard, S. Le – PersonEntity: Name: NameFull: Liu, T. – PersonEntity: Name: NameFull: Marioni, R. E. – PersonEntity: Name: NameFull: Oldmeadow, C. – PersonEntity: Name: NameFull: Postmus, I. – PersonEntity: Name: NameFull: Smith, A. V. – PersonEntity: Name: NameFull: Smith, J. A. – PersonEntity: Name: NameFull: Thalamuthu, A. – PersonEntity: Name: NameFull: Thomson, R. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 02 Text: Feb2015 Type: published Y: 2015 Identifiers: – Type: issn-print Value: 13594184 Numbering: – Type: volume Value: 20 – Type: issue Value: 2 Titles: – TitleFull: Molecular Psychiatry Type: main |
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