期刊
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
卷 159B, 期 6, 页码 684-695出版社
WILEY
DOI: 10.1002/ajmg.b.32072
关键词
GWAS; extraversion; neuroticism; anxiety; depression
资金
- BBSRC [BB/F019394/1, 15/SAG09977]
- Research Into Ageing [251]
- EPSRC
- ESRC
- MRC
- NHMRC [389892, 496682, 496688, 496739, 613672]
- ARC [FT0991022, FT0991360]
- Netherlands Scientific Organization [904-61-090, 904-61-193, 480-04-004, 400-05-717, 912-100-20]
- European Research Council [ERC-230374]
- Centre for Medical Systems Biology
- European Union [EU/WLRT-2001-01254, LSHG-CT-2006-018947]
- ZonMW
- NTR
- NWO SPI [56-464-1419, 480-05-003]
- NWO-VENI [916-76-125]
- Age UK's Disconnected Mind programme
- Social Science Research Council
- Wellcome Trust
- Medical Research Council UK
- Ministry of Science, Education and Sport of the Republic of Croatia [108-1080315-0302]
- Chief Scientist Office of the Scottish Government
- Royal Society
- Centre for Medical Systems Biology (NWO Genomics)
- Neuroscience Campus Amsterdam (NCA)
- EMGO+ institute
- ZonMW(Geestkracht program) [10-000-1002]
- NWO [480-05-003]
- [NWO-SPI 56-464-1419]
- BBSRC [BB/F022441/1, BB/F019394/1] Funding Source: UKRI
- MRC [G0100594, G0901461, G0900753, G0600237, G0700704, G1001375, MC_PC_U127561128] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/F019394/1, BB/F022441/1] Funding Source: researchfish
- Chief Scientist Office [CZB/4/710, CZB/4/505, ETM/55] Funding Source: researchfish
- Medical Research Council [G0901461, G0600237, MC_PC_U127561128, G0900753, G0100594, G0700704, G0700704B, G1001375] Funding Source: researchfish
Measures of personality and psychological distress are correlated and exhibit genetic covariance. We conducted univariate genome-wide SNP (similar to 2.5 million) and gene-based association analyses of these traits and examined the overlap in results across traits, including a prediction analysis of mood states using genetic polygenic scores for personality. Measures of neuroticism, extraversion, and symptoms of anxiety, depression, and general psychological distress were collected in eight European cohorts (n ranged 546-1,338; maximum total n = 6,268) whose mean age ranged from 55 to 79 years. Meta-analysis of the cohort results was performed, with follow-up associations of the top SNPs and genes investigated in independent cohorts (n = 527-6,032). Suggestive association (P = 8 x 10(-8)) of rs1079196 in the FHIT gene was observed with symptoms of anxiety. Other notable associations (P < 6.09 x 10(-6)) included SNPs in five genes for neuroticism (LCE3C, POLR3A, LMAN1L, ULK3, SCAMP2), KIAA0802 for extraversion, and NOS1 for general psychological distress. An association between symptoms of depression and rs7582472 (near to MGAT5 and NCKAP5) was replicated in two independent samples, but other replication findings were less consistent. Gene-based tests identified a significant locus on chromosome 15 (spanning five genes) associated with neuroticism which replicated (P < 0.05) in an independent cohort. Support for common genetic effects among personality and mood (particularly neuroticism and depressive symptoms) was found in terms of SNP association overlap and polygenic score prediction. The variance explained by individual SNPs was very small (up to 1%) confirming that there are no moderate/large effects of common SNPs on personality and related traits. (C) 2012 Wiley Periodicals, Inc.
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