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

Publication ,  Journal Article
Trampush, JW; Yang, MLZ; Yu, J; Knowles, E; Davies, G; Liewald, DC; Starr, JM; Djurovic, S; Melle, I; Sundet, K; Christoforou, A; Reinvang, I ...
Published in: Mol Psychiatry
March 2017

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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Published In

Mol Psychiatry

DOI

EISSN

1476-5578

Publication Date

March 2017

Volume

22

Issue

3

Start / End Page

336 / 345

Location

England

Related Subject Headings

  • White People
  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Neurocognitive Disorders
  • Multifactorial Inheritance
  • Middle Aged
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Variation
 

Citation

APA
Chicago
ICMJE
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Trampush, J. W., Yang, M. L. Z., Yu, J., Knowles, E., Davies, G., Liewald, D. C., … Lencz, T. (2017). GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium. Mol Psychiatry, 22(3), 336–345. https://doi.org/10.1038/mp.2016.244
Trampush, J. W., M. L. Z. Yang, J. Yu, E. Knowles, G. Davies, D. C. Liewald, J. M. Starr, et al. “GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium.Mol Psychiatry 22, no. 3 (March 2017): 336–45. https://doi.org/10.1038/mp.2016.244.
Trampush JW, Yang MLZ, Yu J, Knowles E, Davies G, Liewald DC, et al. GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium. Mol Psychiatry. 2017 Mar;22(3):336–45.
Trampush, J. W., et al. “GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium.Mol Psychiatry, vol. 22, no. 3, Mar. 2017, pp. 336–45. Pubmed, doi:10.1038/mp.2016.244.
Trampush JW, Yang MLZ, Yu J, Knowles E, Davies G, Liewald DC, Starr JM, Djurovic S, Melle I, Sundet K, Christoforou A, Reinvang I, DeRosse P, Lundervold AJ, Steen VM, Espeseth T, Räikkönen K, Widen E, Palotie A, Eriksson JG, Giegling I, Konte B, Roussos P, Giakoumaki S, Burdick KE, Payton A, Ollier W, Horan M, Chiba-Falek O, Attix DK, Need AC, Cirulli ET, Voineskos AN, Stefanis NC, Avramopoulos D, Hatzimanolis A, Arking DE, Smyrnis N, Bilder RM, Freimer NA, Cannon TD, London E, Poldrack RA, Sabb FW, Congdon E, Conley ED, Scult MA, Dickinson D, Straub RE, Donohoe G, Morris D, Corvin A, Gill M, Hariri AR, Weinberger DR, Pendleton N, Bitsios P, Rujescu D, Lahti J, Le Hellard S, Keller MC, Andreassen OA, Deary IJ, Glahn DC, Malhotra AK, Lencz T. GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium. Mol Psychiatry. 2017 Mar;22(3):336–345.

Published In

Mol Psychiatry

DOI

EISSN

1476-5578

Publication Date

March 2017

Volume

22

Issue

3

Start / End Page

336 / 345

Location

England

Related Subject Headings

  • White People
  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Neurocognitive Disorders
  • Multifactorial Inheritance
  • Middle Aged
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Variation