Sparse whole-genome sequencing identifies two loci for major depressive disorder.
Sparse whole-genome sequencing identifies two loci for major depressive disorder.
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稀疏全基因组测序确定了重度抑郁症的两个基因座
DOI：
10.1038/nature14659
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发表时间：
2015-07-30
期刊：
影响因子：
64.8
通讯作者：
CONVERGE consortium
中科院分区：
文献类型：
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作者：
CONVERGE consortium
重度抑郁症（MDD）是最常见的精神疾病之一，也是全球残疾的主要原因，对遗传分析构成了重大挑战。迄今为止，尽管对9,000多个病例进行了分析，但还没有发现稳健复制的遗传位点。使用5，303名中国复发性MDD女性的低覆盖率基因组序列，选择以减少表型异质性，并筛选5，337名对照以排除MDD，我们确定并复制了10号染色体上两个全基因组显著的MDD风险基因座：一个位于SIRT 1基因附近（P值= 2.53×10−10），另一个位于LHPP基因的内含子中（P = 6.45×10−12）。对4,509例重度MDD亚型的分析表明，SIRT 1基因座的遗传信号增加。我们将成功归功于招募了相对同质的重症病例。
Major depressive disorder (MDD), one of the most frequently encountered forms of mental illness and a leading cause of disability worldwide, poses a major challenge to genetic analysis. To date no robustly replicated genetic loci have been identified , despite analysis of more than 9,000 cases. Using low coverage genome sequence of 5,303 Chinese women with recurrent MDD selected to reduce phenotypic heterogeneity, and 5,337 controls screened to exclude MDD, we identified and replicated two genome-wide significant loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene (P-value = 2.53×10−10) the other in an intron of the LHPP gene (P = 6.45×10−12). Analysis of 4,509 cases with a severe subtype of MDD, melancholia, yielded an increased genetic signal at the SIRT1 locus. We attribute our success to the recruitment of relatively homogeneous cases with severe illness.