Abstract
Original language | English |
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Pages (from-to) | 183 - 192 |
Number of pages | 10 |
Journal | Molecular Psychiatry |
Volume | 20 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2015 |
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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=53949). / Davies, Gail; Armstrong, Nicola; Bis, Joshua C; Bressler, Jan; Chouraki, Vincent; Giddaluru, Sudheer; Hofer, Edith; Ibrahim-Verbaas, Carla A; Kirin, Mirna; Lahti, Jari Marko; van der Lee, Sven J; Le Hellard, Stephanie; Liu, Tian; Marioni, Riccardo E; Oldmeadow, Christopher; Postmus, Iris; Smith, Albert Vernon; Smith, Jennifer Ann; Thalamuthu, Anbupalam; Thomson, Russell; Vitart, Veronique; Wang, Jing; Yu, Lei; Zgaga, Lina; Zhao, Wei; Boxall, Ruth; Harris, Sarah E; Hill, William David; Liewald, David C; Luciano, Michelle; Adams, Hieab H H; Ames, David J; Amin, Najaf; Amouyel, Philippe; Assareh, Amelia A; Au, Rhoda; Becker, James T; Beiser, Alexa; Berr, Claudine; Bertram, Lars; Boerwinkle, Eric; Buckley, Brendan M; Campbell, Harry; Corley, Janie; De Jager, Philip Laurence; Dufouil, Carole; Eriksson, Johan Gunnar; Espeseth, Thomas; Faul, Jessica D; Ford, Ian; Gottesman, Rebecca F; Griswold, Michael E; Gudnason, Vilmundur G; Harris, Tamara B; Heiss, Gerardo; Hofman, Albert; Holliday, Elizabeth G; Huffman, Jennifer; Kardia, Sharon L R; Kochan, Nicole; Knopman, David S; Kwok, John B J; Lambert, Jean-Charles; Lee, Teresa; Li, Guo; Li, Shu-Chen; Loitfelder, Marisa; Lopez, Oscar L; Lundervold, Astri Johansen; Lundqvist, Anders; Mather, Karen A; Mirza, Saira Saeed; Nyberg, Lars; Oostra, Ben A; Palotie, Aarno; Papenberg, Goran; Pattie, Alison; Petrovic, Katja Elisabeth; Polasek, Ozren; Psaty, Bruce M; Redmond, Paul; Reppermund, Simone; Rotter, Jerome I; Schmidt, Helena; Schuur, Maaike; Schofield, Peter W; Scott, Rodney J; Steen, Vidar M; Stott, David J; van Swieten, John C; Taylor, Kent D; Trollor, Julian Norman; Trompet, Stella; Uitterlinden, Andre G; Weinstein, Galit; Widen, Elisabeth; Windham, Beverly Gwen; Jukema, J Wouter; Wright, Alan F; Wright, Margaret J; Yang, Qiong; Amieva, Helene; Attia, John R; Bennett, David A; Brodaty, Henry; de Craen, Anton J M; Hayward, Caroline; Ikram, Mohammed Arfan; Nilsson, Lars-Goran; Lindenberger, Ulman; Porteous, David J; Raikkonen, Katri; Reinvang, Ivar; Rudan, Igor; Sachdev, Perminder Singh; Schmidt, Reinhold; Schofield, Peter R; Srikanth, Velandai; Starr, John M; Turner, Stephen T; Weir, David R; Wilson, Jim F; van Duijn, Cornelia M; Launer, Lenore J; Fitzpatrick, Annette L; Seshadri, Sudha; Mosley, Thomas H; Deary, Ian J.
In: Molecular Psychiatry, Vol. 20, No. 2, 2015, p. 183 - 192.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53949)
AU - Davies, Gail
AU - Armstrong, Nicola
AU - Bis, Joshua C
AU - Bressler, Jan
AU - Chouraki, Vincent
AU - Giddaluru, Sudheer
AU - Hofer, Edith
AU - Ibrahim-Verbaas, Carla A
AU - Kirin, Mirna
AU - Lahti, Jari Marko
AU - van der Lee, Sven J
AU - Le Hellard, Stephanie
AU - Liu, Tian
AU - Marioni, Riccardo E
AU - Oldmeadow, Christopher
AU - Postmus, Iris
AU - Smith, Albert Vernon
AU - Smith, Jennifer Ann
AU - Thalamuthu, Anbupalam
AU - Thomson, Russell
AU - Vitart, Veronique
AU - Wang, Jing
AU - Yu, Lei
AU - Zgaga, Lina
AU - Zhao, Wei
AU - Boxall, Ruth
AU - Harris, Sarah E
AU - Hill, William David
AU - Liewald, David C
AU - Luciano, Michelle
AU - Adams, Hieab H H
AU - Ames, David J
AU - Amin, Najaf
AU - Amouyel, Philippe
AU - Assareh, Amelia A
AU - Au, Rhoda
AU - Becker, James T
AU - Beiser, Alexa
AU - Berr, Claudine
AU - Bertram, Lars
AU - Boerwinkle, Eric
AU - Buckley, Brendan M
AU - Campbell, Harry
AU - Corley, Janie
AU - De Jager, Philip Laurence
AU - Dufouil, Carole
AU - Eriksson, Johan Gunnar
AU - Espeseth, Thomas
AU - Faul, Jessica D
AU - Ford, Ian
AU - Gottesman, Rebecca F
AU - Griswold, Michael E
AU - Gudnason, Vilmundur G
AU - Harris, Tamara B
AU - Heiss, Gerardo
AU - Hofman, Albert
AU - Holliday, Elizabeth G
AU - Huffman, Jennifer
AU - Kardia, Sharon L R
AU - Kochan, Nicole
AU - Knopman, David S
AU - Kwok, John B J
AU - Lambert, Jean-Charles
AU - Lee, Teresa
AU - Li, Guo
AU - Li, Shu-Chen
AU - Loitfelder, Marisa
AU - Lopez, Oscar L
AU - Lundervold, Astri Johansen
AU - Lundqvist, Anders
AU - Mather, Karen A
AU - Mirza, Saira Saeed
AU - Nyberg, Lars
AU - Oostra, Ben A
AU - Palotie, Aarno
AU - Papenberg, Goran
AU - Pattie, Alison
AU - Petrovic, Katja Elisabeth
AU - Polasek, Ozren
AU - Psaty, Bruce M
AU - Redmond, Paul
AU - Reppermund, Simone
AU - Rotter, Jerome I
AU - Schmidt, Helena
AU - Schuur, Maaike
AU - Schofield, Peter W
AU - Scott, Rodney J
AU - Steen, Vidar M
AU - Stott, David J
AU - van Swieten, John C
AU - Taylor, Kent D
AU - Trollor, Julian Norman
AU - Trompet, Stella
AU - Uitterlinden, Andre G
AU - Weinstein, Galit
AU - Widen, Elisabeth
AU - Windham, Beverly Gwen
AU - Jukema, J Wouter
AU - Wright, Alan F
AU - Wright, Margaret J
AU - Yang, Qiong
AU - Amieva, Helene
AU - Attia, John R
AU - Bennett, David A
AU - Brodaty, Henry
AU - de Craen, Anton J M
AU - Hayward, Caroline
AU - Ikram, Mohammed Arfan
AU - Nilsson, Lars-Goran
AU - Lindenberger, Ulman
AU - Porteous, David J
AU - Raikkonen, Katri
AU - Reinvang, Ivar
AU - Rudan, Igor
AU - Sachdev, Perminder Singh
AU - Schmidt, Reinhold
AU - Schofield, Peter R
AU - Srikanth, Velandai
AU - Starr, John M
AU - Turner, Stephen T
AU - Weir, David R
AU - Wilson, Jim F
AU - van Duijn, Cornelia M
AU - Launer, Lenore J
AU - Fitzpatrick, Annette L
AU - Seshadri, Sudha
AU - Mosley, Thomas H
AU - Deary, Ian J
PY - 2015
Y1 - 2015
N2 - 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=1 x 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 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.
AB - 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=1 x 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 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.
UR - http://www.nature.com/mp/journal/v20/n2/pdf/mp2014188a.pdf
U2 - 10.1038/mp.2014.188
DO - 10.1038/mp.2014.188
M3 - Article
VL - 20
SP - 183
EP - 192
JO - Molecular Psychiatry
JF - Molecular Psychiatry
SN - 1359-4184
IS - 2
ER -