1. Sparse whole-genome sequencing identifies two loci for major depressive disorder
- Author
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Yi Li, Tieqiao Liu, Qibin Li, Xiaoping Wang, Silviu Alin Bacanu, Bo Du, Jicheng Dong, Hong Sang, Guodong Miao, Lijun Yang, Jian Hu, Kerang Zhang, Yutang Zhang, Xumei Wang, Yiping Chen, Xueyi Wang, Zhengrong Liu, Tao Jiang, Brien P. Riley, Wei Jin, Qiwen Zhang, Jinbei Zhang, Xun Xu, Tiebang Liu, Mark Reimers, Huaqing Meng, Tim B. Bigdeli, Xiaojuan Liu, Shenxun Shi, Zhen Zhang, Danhua Gu, Zhaoyu Gan, Gang Wang, Jun Wang, Fengyu Yu, Han Rong, Xiuqing Zhang, Yingrui Li, Guoping Huang, Jian Wang, Enzhao Cong, Guoqing Jiang, Ye Yin, Jonathan Marchini, Shugui Gao, Qiyi Mei, Hui Zhong, Jianguo Shi, Yunchun Chen, Zhenming Shen, Yan Song, Xiang Fang, Min Cai, Yihan Li, Youhui Li, Jonathan Flint, Donglin Yang, Jieqin Liang, Jianhua Shen, Kenneth S. Kendler, Na Cai, Qiang He, Guangyi Fu, Wei Zhang, Guangbiao Wang, Huanming Yang, Jiyang Pan, Xiaoyan Zhou, Sun Jing, Qi Xu, Wenhua Sang, Xiangchao Gan, Baowei Ha, Liu Ying, Keqing Li, Fuzhong Yang, Chengge Gao, Jingchu Hu, Zhenfei Hu, Xiaohong Hong, Lina Wang, Lanfen Liu, Li Song, Roseann E. Peterson, Chunmei Hu, Ning Sun, Warren W. Kretzschmar, Linmao Wang, Yao Lu, Puyi Qian, Yuan Liu, Wenyuan Wu, L Lv, Qihui Niu, Guibing Chen, Tian Tian, Hong Deng, Todd Webb, Runde Pan, Jingfang Gao, Kan Li, Richard Mott, Jing Xia, Ming Tao, and Gongying Li
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Adult ,China ,Adolescent ,Biology ,Bioinformatics ,behavioral disciplines and activities ,Cohort Studies ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Asian People ,Sirtuin 1 ,mental disorders ,medicine ,Humans ,Gene ,030304 developmental biology ,Whole genome sequencing ,Genetics ,Depressive Disorder ,Depressive Disorder, Major ,0303 health sciences ,Multidisciplinary ,Chromosomes, Human, Pair 10 ,Genome, Human ,Recurrent major depressive disorder ,Intron ,Chromosome ,Sequence Analysis, DNA ,Middle Aged ,medicine.disease ,Introns ,3. Good health ,Inorganic Pyrophosphatase ,Genetic Loci ,Major depressive disorder ,Female ,SIRT1 Gene ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
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. Here, using low-coverage whole-genome sequencing of 5,303 Chinese women with recurrent MDD selected to reduce phenotypic heterogeneity, and 5,337 controls screened to exclude MDD, we identified, and subsequently replicated in an independent sample, two loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene (P = 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.
- Published
- 2015
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