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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Davies, G. (author)

Genetic contributions to variation in general cognitive function : a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)

Article/chapterEnglish2015

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2015-02-03
Springer Science and Business Media LLC,2015
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LIBRIS-ID:oai:DiVA.org:su-115943
https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-115943URI
https://doi.org/10.1038/mp.2014.188DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-101412URI
http://kipublications.ki.se/Default.aspx?queryparsed=id:130782778URI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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AuthorCount:128;
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.

Subject headings and genre

NATURVETENSKAP Biologi hsv//swe
NATURAL SCIENCES Biological Sciences hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Psykiatri hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Psychiatry hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Neurologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Neurology hsv//eng

Added entries (persons, corporate bodies, meetings, titles ...)

Armstrong, N. (author)
Bis, J. C. (author)
Bressler, J. (author)
Chouraki, V. (author)
Giddaluru, S. (author)
Hofer, E. (author)
Ibrahim-Verbaas, C. A. (author)
Kirin, M. (author)
Lahti, J. (author)
van der Lee, S. J. (author)
Le Hellard, S. (author)
Liu, T. (author)
Marioni, R. E. (author)
Oldmeadow, C. (author)
Postmus, I. (author)
Smith, A. V. (author)
Smith, J. A. (author)
Thalamuthu, A. (author)
Thomson, R. (author)
Vitart, V. (author)
Wang, J. (author)
Yu, L. (author)
Zgaga, L. (author)
Zhao, W. (author)
Boxall, R. (author)
Harris, S. E. (author)
Hill, W. D. (author)
Liewald, D. C. (author)
Luciano, M. (author)
Adams, H. (author)
Ames, D. (author)
Amin, N. (author)
Amouyel, P. (author)
Assareh, A. A. (author)
Au, R. (author)
Becker, J. T. (author)
Beiser, A. (author)
Berr, C. (author)
Bertram, L. (author)
Boerwinkle, E. (author)
Buckley, B. M. (author)
Campbell, H. (author)
Corley, J. (author)
De Jager, P. L. (author)
Dufouil, C. (author)
Eriksson, J. G. (author)
Espeseth, T. (author)
Faul, J. D. (author)
Ford, I. (author)
Gottesman, R. F. (author)
Griswold, M. E. (author)
Gudnason, V. (author)
Harris, T. B. (author)
Heiss, G. (author)
Hofman, A. (author)
Holliday, E. G. (author)
Huffman, J. (author)
Kardia, S. L. R. (author)
Kochan, N. (author)
Knopman, D. S. (author)
Kwok, J. B. (author)
Lambert, J-C (author)
Lee, T. (author)
Li, G. (author)
Li, S-C (author)
Loitfelder, M. (author)
Lopez, O. L. (author)
Lundervold, A. J. (author)
Lundquist, AndersUmeå universitet,Umeå centrum för funktionell hjärnavbildning (UFBI)(Swepub:umu)anslst97 (author)
Mather, K. A. (author)
Mirza, S. S. (author)
Nyberg, LarsUmeå universitet,Institutionen för integrativ medicinsk biologi (IMB),Institutionen för strålningsvetenskaper,Umeå centrum för funktionell hjärnavbildning (UFBI)(Swepub:umu)lany0001 (author)
Oostra, B. A. (author)
Palotie, A. (author)
Papenberg, GoranKarolinska Institutet,Stockholms universitet,Centrum för forskning om äldre och åldrande (ARC), (tills m KI),Max Planck Institute for Human Development, Germany (author)
Pattie, A. (author)
Petrovic, K. (author)
Polasek, O. (author)
Psaty, B. M. (author)
Redmond, P. (author)
Reppermund, S. (author)
Rotter, J. I. (author)
Schmidt, H. (author)
Schuur, M. (author)
Schofield, P. W. (author)
Scott, R. J. (author)
Steen, V. M. (author)
Stott, D. J. (author)
Van Swieten, J. C. (author)
Taylor, K. D. (author)
Trollor, J. (author)
Trompet, S. (author)
Uitterlinden, A. G. (author)
Weinstein, G. (author)
Widen, E. (author)
Windham, B. G. (author)
Jukema, J. W. (author)
Wright, A. F. (author)
Wright, M. J. (author)
Yang, Q. (author)
Amieva, H. (author)
Attia, J. R. (author)
Bennett, D. A. (author)
Brodaty, H. (author)
de Craen, A. J. M. (author)
Hayward, C. (author)
Ikram, M. A. (author)
Lindenberger, U. (author)
Nilsson, Lars-GöranUmeå universitet,Umeå centrum för funktionell hjärnavbildning (UFBI),ARC, Karolinska Institutet, Stockholm(Swepub:umu)lani0012 (author)
Porteous, D. J. (author)
Raikkonen, K. (author)
Reinvang, I. (author)
Rudan, I. (author)
Sachdev, P. S. (author)
Schmidt, R. (author)
Schofield, P. R. (author)
Srikanth, V. (author)
Starr, J. M. (author)
Turner, S. T. (author)
Weir, D. R. (author)
Wilson, J. F. (author)
Van Duijn, C. (author)
Launer, L. (author)
Fitzpatrick, A. L. (author)
Seshadri, S. (author)
Jr, T. H. Mosley (author)
Deary, I. J. (author)
Umeå universitetUmeå centrum för funktionell hjärnavbildning (UFBI) (creator_code:org_t)

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In:Molecular Psychiatry: Springer Science and Business Media LLC20:2, s. 183-1921359-41841476-5578

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By the author/editor: Davies, G.; Armstrong, N.; Bis, J. C.; Bressler, J.; Chouraki, V.; Giddaluru, S.; show more...; Hofer, E.; Ibrahim-Verbaas, ...; Kirin, M.; Lahti, J.; van der Lee, S. ...; Le Hellard, S.; Liu, T.; Marioni, R. E.; Oldmeadow, C.; Postmus, I.; Smith, A. V.; Smith, J. A.; Thalamuthu, A.; Thomson, R.; Vitart, V.; Wang, J.; Yu, L.; Zgaga, L.; Zhao, W.; Boxall, R.; Harris, S. E.; Hill, W. D.; Liewald, D. C.; Luciano, M.; Adams, H.; Ames, D.; Amin, N.; Amouyel, P.; Assareh, A. A.; Au, R.; Becker, J. T.; Beiser, A.; Berr, C.; Bertram, L.; Boerwinkle, E.; Buckley, B. M.; Campbell, H.; Corley, J.; De Jager, P. L.; Dufouil, C.; Eriksson, J. G.; Espeseth, T.; Faul, J. D.; Ford, I.; Gottesman, R. F.; Griswold, M. E.; Gudnason, V.; Harris, T. B.; Heiss, G.; Hofman, A.; Holliday, E. G.; Huffman, J.; Kardia, S. L. R.; Kochan, N.; Knopman, D. S.; Kwok, J. B.; Lambert, J-C; Lee, T.; Li, G.; Li, S-C; Loitfelder, M.; Lopez, O. L.; Lundervold, A. J ...; Lundquist, Ander ...; Mather, K. A.; Mirza, S. S.; Nyberg, Lars; Oostra, B. A.; Palotie, A.; Papenberg, Goran; Pattie, A.; Petrovic, K.; Polasek, O.; Psaty, B. M.; Redmond, P.; Reppermund, S.; Rotter, J. I.; Schmidt, H.; Schuur, M.; Schofield, P. W.; Scott, R. J.; Steen, V. M.; Stott, D. J.; Van Swieten, J. ...; Taylor, K. D.; Trollor, J.; Trompet, S.; Uitterlinden, A. ...; Weinstein, G.; Widen, E.; Windham, B. G.; Jukema, J. W.; Wright, A. F.; Wright, M. J.; Yang, Q.; Amieva, H.; Attia, J. R.; Bennett, D. A.; Brodaty, H.; de Craen, A. J. ...; Hayward, C.; Ikram, M. A.; Lindenberger, U.; Nilsson, Lars-Gö ...; Porteous, D. J.; Raikkonen, K.; Reinvang, I.; Rudan, I.; Sachdev, P. S.; Schmidt, R.; Schofield, P. R.; Srikanth, V.; Starr, J. M.; Turner, S. T.; Weir, D. R.; Wilson, J. F.; Van Duijn, C.; Launer, L.; Fitzpatrick, A. ...; Seshadri, S.; Jr, T. H. Mosley; Deary, I. J.; show less...

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