GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: A report from the COGENT consortium
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Published version
Author(s)
Type
Journal Article
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 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). Additionally, 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 genomewide 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. = .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.
Date Issued
2017-01-17
Date Acceptance
2016-11-03
Citation
Molecular Psychiatry, 2017, 22, pp.336-345
ISSN
1476-5578
Publisher
Nature Publishing Group
Start Page
336
End Page
345
Journal / Book Title
Molecular Psychiatry
Volume
22
Copyright Statement
© The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0
International License. The images or other third party material in this
article are included in the article’s Creative Commons license, unless indicated
otherwise in the credit line; if the material is not included under the Creative Commons
license, users will need to obtain permission from the license holder to reproduce the
material. To view a copy of this license, visit http://creativecommons.org/licenses/
by/4.0/
International License. The images or other third party material in this
article are included in the article’s Creative Commons license, unless indicated
otherwise in the credit line; if the material is not included under the Creative Commons
license, users will need to obtain permission from the license holder to reproduce the
material. To view a copy of this license, visit http://creativecommons.org/licenses/
by/4.0/
Subjects
Psychiatry
11 Medical And Health Sciences
06 Biological Sciences
17 Psychology And Cognitive Sciences
Publication Status
Published