• shareshare
  • link
  • cite
  • add
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
Published: 01 Jan 2017
Publisher: Springer

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.

74 references, page 1 of 8

1 Wood AR, Esko T, Yang J, Vedantam S, Pers TH, Gustafsson S et al. Defining the role of common variation in the genomic and biological architecture of adult human height. Nat Genet 2014; 46: 1173-1186. [OpenAIRE]

2 Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR et al. Genetic studies of body mass index yield new insights for obesity biology. Nature 2015; 518: 197-206.

3 Deary IJ, Johnson W, Houlihan LM. Genetic foundations of human intelligence. Hum Genet 2009; 126: 215-232.

4 Davies G, Tenesa A, Payton A, Yang J, Harris SE, Liewald D et al. Genome-wide association studies establish that human intelligence is highly heritable and polygenic. Mol Psychiatry 2011; 16: 996-1005. [OpenAIRE]

5 Lencz T, Knowles E, Davies G, Guha S, Liewald DC, Starr JM et al. Molecular genetic evidence for overlap between general cognitive ability and risk for schizophrenia: a report from the Cognitive Genomics consorTium (COGENT). Mol Psychiatry 2013; 19: 168-174. [OpenAIRE]

6 Benyamin B, Pourcain B, Davis OS, Davies G, Hansell NK, Brion M-JA et al. Childhood intelligence is heritable, highly polygenic and associated with FNBP1L. Mol Psychiatry 2014; 19: 253-258.

7 Davies G, Armstrong N, Bis JC, Bressler J, Chouraki V, Giddaluru S et al. Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N = 53 949). Mol Psychiatry 2015; 20: 183-192. [OpenAIRE]

8 Davies G, Marioni RE, Liewald DC, Hill WD, Hagenaars SP, Harris SE et al. Genomewide association study of cognitive functions and educational attainment in UK Biobank (N = 112 151). Mol Psychiatry 2016; 21: 758-767. [OpenAIRE]

9 Okbay A, Beauchamp JP, Fontana MA, Lee JJ, Pers TH, Rietveld CA et al. Genomewide association study identifies 74 loci associated with educational attainment. Nature 2016; 533: 539-542.

10 Trampush JW, Lencz T, Knowles E, Davies G, Guha S, Pe'er I et al. Independent evidence for an association between general cognitive ability and a genetic locus for educational attainment. Am J Med Genet Part B Neuropsychiatr Genet 2015; 168B: 363-373.

Funded byView all
NIH| 1/2 Schizophrenia Heterogeneity and Toxoplasma Exposure
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01MH092515-03
NIH| Genetic Variation and Functional Disability in Schizophrenia
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01MH079800-04
UKRI| A genome-wide association study of non-pathological cognitive ageing
  • Funder: UK Research and Innovation (UKRI)
  • Project Code: BB/F019394/1
  • Funding stream: BBSRC
NIH| Neural signatures of healthy and unhealthy aging
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1R01AG049789-01
Download from