Sparse whole-genome sequencing identifies two loci for major depressive disorder

Na Cai; Tim B. Bigdeli; Warren Kretzschmar; Yihan Lei; Jieqin Liang; Li Song; Jingchu Hu; Qibin Li; Wei Jin; Zhenfei Hu; Guangbiao Wang; Linmao Wang; Puyi Qian; Yuan Liu; Tao Jiang; Yao Lu; Xiuqing Zhang; Ye Yin; Yingrui Lie; Xun Xu; Jingfang Gao; Mark Reimers; Todd Webb; Brien Riley; Silviu Bacanu; Roseann E. Peterson; Yiping Chen; Hui Zhong; Zhengrong Liu; Gang Wang; Jing Sun; Hong Sang; Guoqing Jiang; Xiaoyan Zhou; Yi Li; Wei Zhang; Xueyi Wang; Xiang Fang; Runde Pan; Guodong Miao; Qiwen Zhang; Jian Hu; Fengyu Yu; Bo Du; Wenhua Sang; Keqing Li; Guibing Chen; Min Cai; Lijun Yang; Donglin Yang; Baowei Ha; Xiaohong Hong; Hong Deng; Gongying Li; Kan Li; Yan Song; Shugui Gao; Jinbei Zhang; Zhaoyu Gan; Huaqing Meng; Jiyang Pan; Chengge Gao; Kerang Zhang; Ning Sun; Youhui Li; Qihui Niu; Yutang Zhang; Tieqiao Liu; Chunmei Hu; Zhen Zhang; Luxian Lv; Jicheng Dong; Xiaoping Wang; Ming Tao; Xumei Wang; Jing Xia; Han Rong; Qiang He; Tiebang Liu; Guoping Huang; Qiyi Mei; Zhenming Shen; Ying Liu; Jianhua Shen; Tian Tian; Xiaojuan Liu; Wenyuan Wu; Danhua Gu; Guangyi Fu; Jianguo Shi; Yunchun Chen; Xiangchao Gan; Lanfen Liu; Lina Wang; Fuzhong Yang; Enzhao Cong; Jonathan Marchini; Huanming Yang; Jian Wang; Shenxun Shi; Richard Mott; Qi Xu; Jun Wang; Kenneth S. Kendler; Jonathan Flint

doi:10.1038/nature14659

Sparse whole-genome sequencing identifies two loci for major depressive disorder

Na Cai
, Tim B. Bigdeli
, Warren Kretzschmar
, Yihan Lei
, Jieqin Liang
, Li Song
, Jingchu Hu
, Qibin Li
, Wei Jin
, Zhenfei Hu
, Guangbiao Wang
, Linmao Wang
, Puyi Qian
, Yuan Liu
, Tao Jiang
, Yao Lu
, Xiuqing Zhang
, Ye Yin
, Yingrui Lie
, Xun Xu

Jingfang Gao, Mark Reimers, Todd Webb, Brien Riley, Silviu Bacanu, Roseann E. Peterson, Yiping Chen, Hui Zhong, Zhengrong Liu, Gang Wang, Jing Sun, Hong Sang, Guoqing Jiang, Xiaoyan Zhou, Yi Li, Wei Zhang, Xueyi Wang, Xiang Fang, Runde Pan, Guodong Miao, Qiwen Zhang, Jian Hu, Fengyu Yu, Bo Du, Wenhua Sang, Keqing Li, Guibing Chen, Min Cai, Lijun Yang, Donglin Yang, Baowei Ha, Xiaohong Hong, Hong Deng, Gongying Li, Kan Li, Yan Song, Shugui Gao, Jinbei Zhang, Zhaoyu Gan, Huaqing Meng, Jiyang Pan, Chengge Gao, Kerang Zhang, Ning Sun, Youhui Li, Qihui Niu, Yutang Zhang, Tieqiao Liu, Chunmei Hu, Zhen Zhang, Luxian Lv, Jicheng Dong, Xiaoping Wang, Ming Tao, Xumei Wang, Jing Xia, Han Rong, Qiang He, Tiebang Liu, Guoping Huang, Qiyi Mei, Zhenming Shen, Ying Liu, Jianhua Shen, Tian Tian, Xiaojuan Liu, Wenyuan Wu, Danhua Gu, Guangyi Fu, Jianguo Shi, Yunchun Chen, Xiangchao Gan, Lanfen Liu, Lina Wang, Fuzhong Yang, Enzhao Cong, Jonathan Marchini, Huanming Yang, Jian Wang, Shenxun Shi, Richard Mott, Qi Xu, Jun Wang, Kenneth S. Kendler, Jonathan Flint

University of Oxford
Virginia Commonwealth University
BGI-Shenzhen
Zhejiang Traditional Chinese Medical Hospital
Anhui Mental Health Center
Anshan Psychiatric Rehabilitation Hospital
Capital Medical University
Nanjing Medical University
Changchun Mental Hospital
Chongqing Mental Health Center
Dalian No.7 Hospital
Wuhan Mental Health Center
Daqing No. 3 Hospital of Heilongjiang Province
Hebei Medical University
Fuzhou Psychiatric Hospital
Guangxi Longquanshan Hospital
Guangzhou Psychiatric Hospital
Hainan Anning Hospital
Harbin Medical University
Harbin No. 1 Special Hospital
Hebei Mental Health Center
Huaian No. 3 Hospital
Huzhou No. 3 Hospital
Jilin Brain Hospital
Jining Psychiatric Hospital
Liaocheng No Hospital
Shantou University
Sichuan University
Jining Medical College
Mental Hospital of Jiangxi Province
Mudanjiang Psychiatric Hospital of Heilongjiang Province
Ningbo Kang Ning Hospital
The Third Affiliated Hospital of Sun Yat-sen University
Chongqing Medical University
The First Affiliated Hospital of Jinan University
Xi'an Jiaotong University
Shanxi Medical University
Zhengzhou University
Lanzhou University
Central South University
No. 3 Hospital of Heilongjiang Province
No.4 Hospital of Jiangsu University
Psychiatric Hospital of Henan Province
Qingdao Mental Health Center
Renmin Hospital of Wuhan University
Zhejiang Chinese Medical University
China Medical University
Shenzhen University
Kanazawa Medical University
Sichuan Mental Health Center
Suzhou Guangji Hospital
Tangshan No.5 Hospital
Tianjin Anding Hospital
Tianjin First Central Hospital
Tongji University
ETDZ
Xian Mental Health Center
Air Force Medical University
Max Planck Institute for Plant Breeding Research
Shandong Mental Health Center
Shanghai Jiao Tong University
Huashan Hospital
Chinese Academy of Medical Sciences
University of Copenhagen
Macau University of Science and Technology
King Abdulaziz University
East China Normal University

Research output: Contribution to journal › Article › peer-review

733 Scopus citations

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 identified², despite analysis of more than 9,000 cases³. 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.

Original language	English
Pages (from-to)	588-591
Number of pages	4
Journal	Nature
Volume	523
Issue number	7562
DOIs	https://doi.org/10.1038/nature14659
State	Published - 30 Jul 2015
Externally published	Yes

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1038/nature14659

Cite this

@article{a6a1854252124beab3fdf98c9c7a9bbc,

title = "Sparse whole-genome sequencing identifies two loci for major depressive disorder",

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 identified2, despite analysis of more than 9,000 cases3. 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 {\texttimes} 10-10), the other in an intron of the LHPP gene (P = 6.45 {\texttimes} 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.",

author = "Na Cai and Bigdeli, \{Tim B.\} and Warren Kretzschmar and Yihan Lei and Jieqin Liang and Li Song and Jingchu Hu and Qibin Li and Wei Jin and Zhenfei Hu and Guangbiao Wang and Linmao Wang and Puyi Qian and Yuan Liu and Tao Jiang and Yao Lu and Xiuqing Zhang and Ye Yin and Yingrui Lie and Xun Xu and Jingfang Gao and Mark Reimers and Todd Webb and Brien Riley and Silviu Bacanu and Peterson, \{Roseann E.\} and Yiping Chen and Hui Zhong and Zhengrong Liu and Gang Wang and Jing Sun and Hong Sang and Guoqing Jiang and Xiaoyan Zhou and Yi Li and Wei Zhang and Xueyi Wang and Xiang Fang and Runde Pan and Guodong Miao and Qiwen Zhang and Jian Hu and Fengyu Yu and Bo Du and Wenhua Sang and Keqing Li and Guibing Chen and Min Cai and Lijun Yang and Donglin Yang and Baowei Ha and Xiaohong Hong and Hong Deng and Gongying Li and Kan Li and Yan Song and Shugui Gao and Jinbei Zhang and Zhaoyu Gan and Huaqing Meng and Jiyang Pan and Chengge Gao and Kerang Zhang and Ning Sun and Youhui Li and Qihui Niu and Yutang Zhang and Tieqiao Liu and Chunmei Hu and Zhen Zhang and Luxian Lv and Jicheng Dong and Xiaoping Wang and Ming Tao and Xumei Wang and Jing Xia and Han Rong and Qiang He and Tiebang Liu and Guoping Huang and Qiyi Mei and Zhenming Shen and Ying Liu and Jianhua Shen and Tian Tian and Xiaojuan Liu and Wenyuan Wu and Danhua Gu and Guangyi Fu and Jianguo Shi and Yunchun Chen and Xiangchao Gan and Lanfen Liu and Lina Wang and Fuzhong Yang and Enzhao Cong and Jonathan Marchini and Huanming Yang and Jian Wang and Shenxun Shi and Richard Mott and Qi Xu and Jun Wang and Kendler, \{Kenneth S.\} and Jonathan Flint",

year = "2015",

month = jul,

day = "30",

doi = "10.1038/nature14659",

language = "英语",

volume = "523",

pages = "588--591",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "7562",

}

Cai, N, Bigdeli, TB, Kretzschmar, W, Lei, Y, Liang, J, Song, L, Hu, J, Li, Q, Jin, W, Hu, Z, Wang, G, Wang, L, Qian, P, Liu, Y, Jiang, T, Lu, Y, Zhang, X, Yin, Y, Lie, Y, Xu, X, Gao, J, Reimers, M, Webb, T, Riley, B, Bacanu, S, Peterson, RE, Chen, Y, Zhong, H, Liu, Z, Wang, G, Sun, J, Sang, H, Jiang, G, Zhou, X, Li, Y, Zhang, W, Wang, X, Fang, X, Pan, R, Miao, G, Zhang, Q, Hu, J, Yu, F, Du, B, Sang, W, Li, K, Chen, G, Cai, M, Yang, L, Yang, D, Ha, B, Hong, X, Deng, H, Li, G, Li, K, Song, Y, Gao, S, Zhang, J, Gan, Z, Meng, H, Pan, J, Gao, C, Zhang, K, Sun, N, Li, Y, Niu, Q, Zhang, Y, Liu, T, Hu, C, Zhang, Z, Lv, L, Dong, J, Wang, X, Tao, M, Wang, X, Xia, J, Rong, H, He, Q, Liu, T, Huang, G, Mei, Q, Shen, Z, Liu, Y, Shen, J, Tian, T, Liu, X, Wu, W, Gu, D, Fu, G, Shi, J, Chen, Y, Gan, X, Liu, L, Wang, L, Yang, F, Cong, E, Marchini, J, Yang, H, Wang, J, Shi, S, Mott, R, Xu, Q, Wang, J, Kendler, KS & Flint, J 2015, 'Sparse whole-genome sequencing identifies two loci for major depressive disorder', Nature, vol. 523, no. 7562, pp. 588-591. https://doi.org/10.1038/nature14659

TY - JOUR

T1 - Sparse whole-genome sequencing identifies two loci for major depressive disorder

AU - Cai, Na

AU - Bigdeli, Tim B.

AU - Kretzschmar, Warren

AU - Lei, Yihan

AU - Liang, Jieqin

AU - Song, Li

AU - Hu, Jingchu

AU - Li, Qibin

AU - Jin, Wei

AU - Hu, Zhenfei

AU - Wang, Guangbiao

AU - Wang, Linmao

AU - Qian, Puyi

AU - Liu, Yuan

AU - Jiang, Tao

AU - Lu, Yao

AU - Zhang, Xiuqing

AU - Yin, Ye

AU - Lie, Yingrui

AU - Xu, Xun

AU - Gao, Jingfang

AU - Reimers, Mark

AU - Webb, Todd

AU - Riley, Brien

AU - Bacanu, Silviu

AU - Peterson, Roseann E.

AU - Chen, Yiping

AU - Zhong, Hui

AU - Liu, Zhengrong

AU - Wang, Gang

AU - Sun, Jing

AU - Sang, Hong

AU - Jiang, Guoqing

AU - Zhou, Xiaoyan

AU - Li, Yi

AU - Zhang, Wei

AU - Wang, Xueyi

AU - Fang, Xiang

AU - Pan, Runde

AU - Miao, Guodong

AU - Zhang, Qiwen

AU - Hu, Jian

AU - Yu, Fengyu

AU - Du, Bo

AU - Sang, Wenhua

AU - Li, Keqing

AU - Chen, Guibing

AU - Cai, Min

AU - Yang, Lijun

AU - Yang, Donglin

AU - Ha, Baowei

AU - Hong, Xiaohong

AU - Deng, Hong

AU - Li, Gongying

AU - Li, Kan

AU - Song, Yan

AU - Gao, Shugui

AU - Zhang, Jinbei

AU - Gan, Zhaoyu

AU - Meng, Huaqing

AU - Pan, Jiyang

AU - Gao, Chengge

AU - Zhang, Kerang

AU - Sun, Ning

AU - Li, Youhui

AU - Niu, Qihui

AU - Zhang, Yutang

AU - Liu, Tieqiao

AU - Hu, Chunmei

AU - Zhang, Zhen

AU - Lv, Luxian

AU - Dong, Jicheng

AU - Wang, Xiaoping

AU - Tao, Ming

AU - Wang, Xumei

AU - Xia, Jing

AU - Rong, Han

AU - He, Qiang

AU - Liu, Tiebang

AU - Huang, Guoping

AU - Mei, Qiyi

AU - Shen, Zhenming

AU - Liu, Ying

AU - Shen, Jianhua

AU - Tian, Tian

AU - Liu, Xiaojuan

AU - Wu, Wenyuan

AU - Gu, Danhua

AU - Fu, Guangyi

AU - Shi, Jianguo

AU - Chen, Yunchun

AU - Gan, Xiangchao

AU - Liu, Lanfen

AU - Wang, Lina

AU - Yang, Fuzhong

AU - Cong, Enzhao

AU - Marchini, Jonathan

AU - Yang, Huanming

AU - Wang, Jian

AU - Shi, Shenxun

AU - Mott, Richard

AU - Xu, Qi

AU - Wang, Jun

AU - Kendler, Kenneth S.

AU - Flint, Jonathan

PY - 2015/7/30

Y1 - 2015/7/30

N2 - 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 identified2, despite analysis of more than 9,000 cases3. 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.

AB - 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 identified2, despite analysis of more than 9,000 cases3. 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.

UR - https://www.scopus.com/pages/publications/84938379545

U2 - 10.1038/nature14659

DO - 10.1038/nature14659

M3 - 文章

C2 - 26176920

AN - SCOPUS:84938379545

SN - 0028-0836

VL - 523

SP - 588

EP - 591

JO - Nature

JF - Nature

IS - 7562

ER -

Sparse whole-genome sequencing identifies two loci for major depressive disorder

Abstract

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