Large-scale genomics unveils the genetic architecture of psychiatric disorders

被引：259

作者：

Gratten, Jacob ^{[1
]}

Wray, Naomi R. ^{[1
]}

Keller, Matthew C. ^{[2
]}

Visscher, Peter M. ^{[1
,3
]}

机构：

[1] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia

[2] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA

[3] Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld, Australia

来源：

NATURE NEUROSCIENCE | 2014年 / 17卷 / 06期

基金：

美国国家卫生研究院; 英国医学研究理事会; 澳大利亚研究理事会;

关键词：

DE-NOVO MUTATIONS; DEFICIT HYPERACTIVITY DISORDER; AUTISM SPECTRUM DISORDERS; WIDE ASSOCIATION; BIPOLAR DISORDER; COMMON SNPS; ALZHEIMERS-DISEASE; RARE VARIANTS; COMPLEX TRAIT; PATERNAL AGE;

D O I：

10.1038/nn.3708

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Family study results are consistent with genetic effects making substantial contributions to risk of psychiatric disorders such as schizophrenia, yet robust identification of specific genetic variants that explain variation in population risk had been disappointing until the advent of technologies that assay the entire genome in large samples. We highlight recent progress that has led to a better understanding of the number of risk variants in the population and the interaction of allele frequency and effect size. The emerging genetic architecture implies a large number of contributing loci (that is, a high genome-wide mutational target) and suggests that genetic risk of psychiatric disorders involves the combined effects of many common variants of small effect, as well as rare and de novo variants of large effect. The capture of a substantial proportion of genetic risk facilitates new study designs to investigate the combined effects of genes and the environment.

引用

页码：782 / 790

页数：9

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