期刊
MOLECULAR PSYCHIATRY
卷 22, 期 3, 页码 336-345出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2016.244
关键词
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资金
- National Institutes of Health [R01MH079800, P50 MH080173, R01 MH080912, K23 MH077807, K01 MH085812, R01 DA033369, R01 AG049789]
- Research Council of Norway
- South-East Norway Health Authority
- KG Jebsen Foundation
- Research Council of Norway [154313/V50, 177458/V50]
- Bergen Research Foundation
- University of Bergen
- Research Council of Norway (FUGE, Psykisk Helse)
- Helse Vest RHF and Dr Einar Martens Fund
- Academy of Finland
- Finnish Diabetes Research Society
- Folkhalsan Research Foundation
- Novo Nordisk Foundation
- Finska Lakaresallskapet
- Signe and Ane Gyllenberg Foundation
- University of Helsinki
- Ministry of Education
- Ahokas Foundation
- Emil Aaltonen Foundation
- Disconnected Mind project
- UK Biotechnology and Biological Sciences Research Council (BBSRC) [BB/F019394/1]
- Medical Research Council
- Biotechnology and Biological Sciences Research Council [MR/K026992/1]
- CAMH Foundation
- Canadian Institutes of Health Research
- National Institute of Mental Health of the National Institutes of Health [K01MH098126]
- Ellison Medical Foundation New Scholar award [AG-NS-0441-08]
- NIH [UL1DE019580, PL1MH083271, RL1MH083269, RL1DA024853, PL1NS062410]
- National Institute of Mental Health research [R01MH085018, R01MH092515]
- National Science Foundation Graduate Research Fellowship
- Science Foundation Ireland [12/IP/1670, 12/IP/1359, 08/IN. 1/B1916]
- BBSRC [BB/F019394/1, BB/F022441/1] Funding Source: UKRI
- Science Foundation Ireland (SFI) [12/IP/1670, 12/IP/1359] Funding Source: Science Foundation Ireland (SFI)
- Biotechnology and Biological Sciences Research Council [BB/F022441/1, BB/F019394/1] Funding Source: researchfish
- Medical Research Council [MC_qA137853, MR/K026992/1] Funding Source: researchfish
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 (similar to 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<5x10(-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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