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Other research product . Other ORP type . 2017

GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report form the COGENT consortium

Trampush, Joey W.; Yang, M.L.Z.; Yu, Jin; Knowles, Emma; Davies, Gail; Liewald, David C.M.; Starr, John M.; +59 Authors
Open Access
English
Published: 01 Jan 2017
Publisher: Springer
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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Funded byView all
NIH| 1/2 Schizophrenia Heterogeneity and Toxoplasma Exposure
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01MH092515-03
  • Funding stream: NATIONAL INSTITUTE OF MENTAL HEALTH
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NIH| Genetic Variation and Functional Disability in Schizophrenia
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01MH079800-04
  • Funding stream: NATIONAL INSTITUTE OF MENTAL HEALTH
,
UKRI| A genome-wide association study of non-pathological cognitive ageing
Project
  • Funder: UK Research and Innovation (UKRI)
  • Project Code: BB/F019394/1
  • Funding stream: BBSRC
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NIH| Neural signatures of healthy and unhealthy aging
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1R01AG049789-01
  • Funding stream: NATIONAL INSTITUTE ON AGING
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