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Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)
- Source :
- Davies , G , Armstrong , N , Bis , JC , Bressler , J , Chouraki , V , Giddaluru , S , Hofer , E , Verbaas , C , Kirin , M , Lahti , J , van der Lee , S , Le Hellard , S , Liu , T , Marioni , RE , Oldmeadow , C , Postmus , I , Smith , AV , Smith , JA , Thalamuthu , A , Thomson , R , Vitart , V , Wang , J , Yu , L , Zgaga , L , Zhao , W , Boxall , R , Harris , SE , Hill , WD , Liewald , DC , Luciano , M , Adams , H , Ames , D , Amin , N , Amouyel , P , Assareh , AA , Au , R , Becker , JT , Beiser , A , Berr , C , Bertram , L , Boerwinkle , E , Buckley , BM , Campbell , H , Corley , J , De Jager , PL , Dufouil , C , Eriksson , JG , Espeseth , T , Faul , JD , Ford , I , Gottesman , RF , Griswold , ME , Gudnason , V , Harris , TB , Heiss , G , Hofman , B , Holliday , EG , Huffman , J , Kardia , SLR , Kochan , N , Knopman , DS , Kwok , JB , Lambert , JC , Lee , T , Li , G , Li , S , Loitfelder , M , Lopez , OL , Lundervold , AJ , Lundqvist , A , Mather , KA , Mirza , S , Nyberg , L , Oostra , B , Palotie , A , Papenberg , G , Pattie , A , Petrovic , K , Polasek , O , Psaty , BM , Redmond , P , Reppermund , S , Rotter , JI , Schmidt , H , Schuur , M , Schofield , PW , Scott , RJ , Steen , VM , Stott , DJ , van Swieten , J C , Taylor , KD , Trollor , J , Trompet , S , Uitterlinden , A , Weinstein , G , Widen , E , Windham , BG , Jukema , JW , Wright , AF , Wright , MJ , Yang , Q , Amieva , H , Attia , JR , Bennett , DA , Brodaty , H , de Craen , AJM , Hayward , C , Ikram , A , Lindenberger , U , Nilsson , LG , Porteous , DJ , Raikkonen , K , Reinvang , I , Rudan , I , Sachdev , PS , Schmidt , R , Schofield , PR , Srikanth , V , Starr , JM , Turner , ST , Weir , DR , Wilson , JF , Duijn , C , Launer , L , Fitzpatrick , AL , Seshadri , S , Mosely , TH & Deary , IJ 2015 , ' Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949) ' , Molecular Psychiatry , vol. 20 , no. 2 , pp. 183-
- Publication Year :
- 2015
-
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 x 10(-9), MIR2113; rs17522122, P = 2.55 x 10(-8), AKAP6; rs10119, P = 5.67 x 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P = 1x10(-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, similar to 1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N = 5487; P = 1.5 x 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.
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- OAIster
- Journal :
- Davies , G , Armstrong , N , Bis , JC , Bressler , J , Chouraki , V , Giddaluru , S , Hofer , E , Verbaas , C , Kirin , M , Lahti , J , van der Lee , S , Le Hellard , S , Liu , T , Marioni , RE , Oldmeadow , C , Postmus , I , Smith , AV , Smith , JA , Thalamuthu , A , Thomson , R , Vitart , V , Wang , J , Yu , L , Zgaga , L , Zhao , W , Boxall , R , Harris , SE , Hill , WD , Liewald , DC , Luciano , M , Adams , H , Ames , D , Amin , N , Amouyel , P , Assareh , AA , Au , R , Becker , JT , Beiser , A , Berr , C , Bertram , L , Boerwinkle , E , Buckley , BM , Campbell , H , Corley , J , De Jager , PL , Dufouil , C , Eriksson , JG , Espeseth , T , Faul , JD , Ford , I , Gottesman , RF , Griswold , ME , Gudnason , V , Harris , TB , Heiss , G , Hofman , B , Holliday , EG , Huffman , J , Kardia , SLR , Kochan , N , Knopman , DS , Kwok , JB , Lambert , JC , Lee , T , Li , G , Li , S , Loitfelder , M , Lopez , OL , Lundervold , AJ , Lundqvist , A , Mather , KA , Mirza , S , Nyberg , L , Oostra , B , Palotie , A , Papenberg , G , Pattie , A , Petrovic , K , Polasek , O , Psaty , BM , Redmond , P , Reppermund , S , Rotter , JI , Schmidt , H , Schuur , M , Schofield , PW , Scott , RJ , Steen , VM , Stott , DJ , van Swieten , J C , Taylor , KD , Trollor , J , Trompet , S , Uitterlinden , A , Weinstein , G , Widen , E , Windham , BG , Jukema , JW , Wright , AF , Wright , MJ , Yang , Q , Amieva , H , Attia , JR , Bennett , DA , Brodaty , H , de Craen , AJM , Hayward , C , Ikram , A , Lindenberger , U , Nilsson , LG , Porteous , DJ , Raikkonen , K , Reinvang , I , Rudan , I , Sachdev , PS , Schmidt , R , Schofield , PR , Srikanth , V , Starr , JM , Turner , ST , Weir , DR , Wilson , JF , Duijn , C , Launer , L , Fitzpatrick , AL , Seshadri , S , Mosely , TH & Deary , IJ 2015 , ' Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949) ' , Molecular Psychiatry , vol. 20 , no. 2 , pp. 183-
- Notes :
- application/pdf, und
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.on1313618727
- Document Type :
- Electronic Resource