Davies, GArmstrong, NBis, J CBressler, JChouraki, VGiddaluru, SHofer, EIbrahim-Verbaas, C AKirin, MLahti, Jvan der Lee, S JLe Hellard, SLiu, TMarioni, R EOldmeadow, CPostmus, ISmith, A VSmith, J AThalamuthu, AThomson, RVitart, VWang, JYu, LZgaga, LZhao, WBoxall, RHarris, S EHill, W DLiewald, D CLuciano, MAdams, HAmes, DAmin, NAmouyel, PAssareh, A AAu, RBecker, J TBeiser, ABerr, CBertram, LBoerwinkle, EBuckley, B MCampbell, HCorley, JDe Jager, P LDufouil, CEriksson, J GEspeseth, TFaul, J DFord, IScotland, GenerationGottesman, R FGriswold, M EGudnason, VHarris, T BHeiss, GHofman, AHolliday, E GHuffman, JKardia, S L RKochan, NKnopman, D SKwok, J BLambert, J-CLee, TLi, GLi, S-CLoitfelder, MLopez, O LLundervold, A JLundqvist, AMather, K AMirza, S SNyberg, LOostra, B APalotie, APapenberg, GPattie, APetrovic, KPolasek, OPsaty, B MRedmond, PReppermund, SRotter, J ISchmidt, HSchuur, MSchofield, P WScott, R JSteen, V MStott, D Jvan Swieten, J CTaylor, K DTrollor, JTrompet, SUitterlinden, A GWeinstein, GWiden, EWindham, B GJukema, J WWright, A FWright, M JYang, QAmieva, HAttia, J RBennett, D ABrodaty, Hde Craen, A J MHayward, CIkram, M ALindenberger, UNilsson, L-GPorteous, D JRäikkönen, KReinvang, IRudan, ISachdev, P SSchmidt, RSchofield, P RSrikanth, VStarr, J MTurner, S TWeir, D RWilson, J Fvan Duijn, CLauner, LFitzpatrick, A LSeshadri, SMosley, T HDeary, I J2015-04-012015Davies, G., N. Armstrong, J. C. Bis, J. Bressler, V. Chouraki, S. Giddaluru, E. Hofer, et al. 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 20 (2): 183-192. doi:10.1038/mp.2014.188. http://dx.doi.org/10.1038/mp.2014.188.1359-4184http://nrs.harvard.edu/urn-3:HUL.InstRepos:14351196General 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; rs17522122, P=2.55 × 10−8, AKAP6; rs10119, P=5.67 × 10−9, APOE/TOMM40). We 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.en-USJournal Article2015-04-0110.1038/mp.2014.188