期刊
MOLECULAR PSYCHIATRY
卷 13, 期 3, 页码 302-312出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.mp.4002048
关键词
neuroticism; whole genome association; DNA pooling; personality; quantitative trait; PDE4D
资金
- NIDA NIH HHS [R01 DA018673, R37 DA018673] Funding Source: Medline
- Wellcome Trust [079912] Funding Source: Medline
We describe a multistage approach to identify single nucleotide polymorphisms (SNPs) associated with neuroticism, a personality trait that shares genetic determinants with major depression and anxiety disorders. Whole genome association with 452 574 SNPs was performed on DNA pools from similar to 2000 individuals selected on extremes of neuroticism scores from a cohort of 88 142 people from southwest England. The most significant SNPs were then genotyped on independent samples to replicate findings. We were able to replicate association of one SNP within the PDE4D gene in a second sample collected by our laboratory and in a family-based test in an independent sample; however, the SNP was not significantly associated with neuroticism in two other independent samples. We also observed an enrichment of low P-values in known regions of copy number variations. Simulation indicates that our study had similar to 80% power to identify neuroticism loci in the genome with odds ratio (OR) > 2, and similar to 50% power to identify small effects (OR = 1.5). Since we failed to find any loci accounting for more than 1% of the variance, the heritability of neuroticism probably arises from many loci each explaining much less than 1%. Our findings argue the need for much larger samples than anticipated in genetic association studies and that the biological basis of emotional disorders is extremely complex.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据