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GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium.
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In: Molecular psychiatry, vol 22, iss 3 (2017)
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Gwas meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the cogent consortium
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GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium
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Trampush, J W; Yang, M L Z; Yu, J; Knowles, E; Davies, G; Liewald, D C; Starr, J M; Djurovic, S; Melle, I; Sundet, K; Christoforou, A; Reinvang, I; DeRosse, P; Lundervold, A J; Steen, V M; Espeseth, T; Räikkönen, K; Widen, E; Palotie, A; Eriksson, J G; Giegling, I; Konte, B; Roussos, P; Giakoumaki, S; Burdick, K E; Payton, A; Ollier, W; Horan, M; Chiba-Falek, O; Attix, D K; Need, A C; Cirulli, E T; Voineskos, A N; Stefanis, N C; Avramopoulos, D; Hatzimanolis, A; Arking, D E; Smyrnis, N; Bilder, R M; Freimer, N A; Cannon, T D; London, E; Poldrack, R A; Sabb, F W; Congdon, E; Conley, E D; Scult, M A; Dickinson, D; Straub, R E; Donohoe, G; Morris, D; Corvin, A; Gill, M; Hariri, A R; Weinberger, D R; Pendleton, N; Bitsios, P; Rujescu, D; Lahti, J; Le Hellard, S; Keller, M C; Andreassen, O A; Deary, I J; Glahn, D C; Malhotra, A K; Lencz, T. - : Nature Publishing Group, 2017
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Abstract:
The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (~8M single-nucleotide polymorphisms (SNP) with minor allele frequency ⩾1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome 1) associated with cognitive performance at the genome-wide significance level (P<5 × 10−8). Gene-based analysis identified an additional three Bonferroni-corrected significant loci at chromosomes 17q21.31, 17p13.1 and 1p13.3. Altogether, common variation across the genome resulted in a conservatively estimated SNP heritability of 21.5% (s.e.=0.01%) for general cognitive function. Integration with prior GWAS of cognitive performance and educational attainment yielded several additional significant loci. Finally, we found robust polygenic correlations between cognitive performance and educational attainment, several psychiatric disorders, birth length/weight and smoking behavior, as well as a novel genetic association to the personality trait of openness. These data provide new insight into the genetics of neurocognitive function with relevance to understanding the pathophysiology of neuropsychiatric illness.
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Keyword:
Immediate Communication
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URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5322272/
http://www.ncbi.nlm.nih.gov/pubmed/28093568
https://doi.org/10.1038/mp.2016.244
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Examining non-syndromic autosomal recessive intellectual disability (NS-ARID) genes for an enriched association with intelligence differences
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GWAS-based pathway analysis differentiates between fluid and crystallized intelligence
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Human cognitive ability is influenced by genetic variation in components of postsynaptic signalling complexes assembled by NMDA receptors and MAGUK proteins
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Human cognitive ability is influenced by genetic variation in components of postsynaptic signalling complexes assembled by NMDA receptors and MAGUK proteins
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Genetic copy number variation and general cognitive ability.
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In: PLoS One , 7 (12) , Article e37385 . (2012) (2012)
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Genome-wide association studies establish that human intelligence is highly heritable and polygenic
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In: MOL PSYCHIATR , 16 (10) 996 - 1005. (2011) (2011)
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Genome-wide association studies establish that human intelligence is highly heritable and polygenic
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Cathepsin D exon 2 polymorphism associated with general intelligence in a healthy older population.
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