Identification of 15 genetic loci associated with risk of major depression in individuals of European descent

被引:485
作者
Hyde, Craig L. [1 ]
Nagle, Michael W. [2 ]
Tian, Chao [3 ]
Chen, Xing [1 ]
Paciga, Sara A. [2 ]
Wendland, Jens R. [2 ]
Tung, Joyce Y. [3 ]
Hinds, David A. [3 ]
Perlis, Roy H. [4 ,5 ]
Winslow, Ashley R. [2 ,6 ]
机构
[1] Pfizer Inc, Pfizer Global Res & Dev, Stat, Cambridge, MA USA
[2] Pfizer Inc, Pfizer Global Res & Dev, Human Genet & Computat Biomed, Cambridge, MA USA
[3] 23andMe Inc, Mountain View, CA 94041 USA
[4] Massachusetts Gen Hosp, Ctr Human Genet Res, Ct Expt Drugs & Diagnost, Boston, MA 02114 USA
[5] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA
[6] Univ Penn, Perelman Sch Med, Orphan Dis Ctr, Philadelphia, PA 19104 USA
关键词
MOOD DISORDERS; MEF2C; SCHIZOPHRENIA; EPILEPSY; BURDEN; DORSAL; BRAIN; MEIS2; POWER;
D O I
10.1038/ng.3623
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Despite strong evidence supporting the heritability of major depressive disorder (MDD), previous genome-wide studies were unable to identify risk loci among individuals of European descent. We used self-report data from 75,607 individuals reporting clinical diagnosis of depression and 231,747 individuals reporting no history of depression through 23andMe and carried out meta-analysis of these results with published MDD genome-wide association study results. We identified five independent variants from four regions associated with self-report of clinical diagnosis or treatment for depression. Loci with a P value <1.0 x 10(-5) in the meta-analysis were further analyzed in a replication data set (45,773 cases and 106,354 controls) from 23andMe. A total of 17 independent SNPs from 15 regions reached genome-wide significance after joint analysis over all three data sets. Some of these loci were also implicated in genome-wide association studies of related psychiatric traits. These studies provide evidence for large-scale consumer genomic data as a powerful and efficient complement to data collected from traditional means of ascertainment for neuropsychiatric disease genomics.
引用
收藏
页码:1031 / +
页数:9
相关论文
共 36 条
[1]   Meis2 is a Pax6 co-factor in neurogenesis and dopaminergic periglomerular fate specification in the adult olfactory bulb [J].
Agoston, Zsuzsa ;
Heine, Peer ;
Brill, Monika S. ;
Grebbin, Britta Moyo ;
Hau, Ann-Christin ;
Kallenborn-Gerhardt, Wiebke ;
Schramm, Jasmine ;
Goetz, Magdalena ;
Schulte, Dorothea .
DEVELOPMENT, 2014, 141 (01) :28-38
[2]   Genetic and physical interaction of Meis2, Pax3 and Pax7 during dorsal midbrain development [J].
Agoston, Zsuzsa ;
Li, Naixin ;
Haslinger, Anja ;
Wizenmann, Andrea ;
Schulte, Dorothea .
BMC DEVELOPMENTAL BIOLOGY, 2012, 12
[3]   An integrated map of genetic variation from 1,092 human genomes [J].
Altshuler, David M. ;
Durbin, Richard M. ;
Abecasis, Goncalo R. ;
Bentley, David R. ;
Chakravarti, Aravinda ;
Clark, Andrew G. ;
Donnelly, Peter ;
Eichler, Evan E. ;
Flicek, Paul ;
Gabriel, Stacey B. ;
Gibbs, Richard A. ;
Green, Eric D. ;
Hurles, Matthew E. ;
Knoppers, Bartha M. ;
Korbel, Jan O. ;
Lander, Eric S. ;
Lee, Charles ;
Lehrach, Hans ;
Mardis, Elaine R. ;
Marth, Gabor T. ;
McVean, Gil A. ;
Nickerson, Deborah A. ;
Schmidt, Jeanette P. ;
Sherry, Stephen T. ;
Wang, Jun ;
Wilson, Richard K. ;
Gibbs, Richard A. ;
Dinh, Huyen ;
Kovar, Christie ;
Lee, Sandra ;
Lewis, Lora ;
Muzny, Donna ;
Reid, Jeff ;
Wang, Min ;
Wang, Jun ;
Fang, Xiaodong ;
Guo, Xiaosen ;
Jian, Min ;
Jiang, Hui ;
Jin, Xin ;
Li, Guoqing ;
Li, Jingxiang ;
Li, Yingrui ;
Li, Zhuo ;
Liu, Xiao ;
Lu, Yao ;
Ma, Xuedi ;
Su, Zhe ;
Tai, Shuaishuai ;
Tang, Meifang .
NATURE, 2012, 491 (7422) :56-65
[4]   Mortality of patients with mood disorders: follow-up over 34-38 years [J].
Angst, F ;
Stassen, HH ;
Clayton, PJ ;
Angst, J .
JOURNAL OF AFFECTIVE DISORDERS, 2002, 68 (2-3) :167-181
[5]  
[Anonymous], 2014, ANCESTRY COMPOSITION
[6]  
[Anonymous], 2002, Meta-Analysis of Controlled Clinical Trials
[7]   MEF2C, a transcription factor that facilitates learning and memory by negative regulation of synapse numbers and function [J].
Barbosa, Ana C. ;
Kim, Mi-Sung ;
Ertunc, Mert ;
Adachi, Megumi ;
Nelson, Erika D. ;
McAnally, John ;
Richardson, James A. ;
Kavalali, Ege T. ;
Monteggia, Lisa M. ;
Bassel-Duby, Rhonda ;
Olson, Eric N. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (27) :9391-9396
[8]   Rapid and accurate haplotype phasing and missing-data inference for whole-genome association studies by use of localized haplotype clustering [J].
Browning, Sharon R. ;
Browning, Brian L. .
AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 81 (05) :1084-1097
[9]   LD Score regression distinguishes confounding from polygenicity in genome-wide association studies [J].
Bulik-Sullivan, Brendan K. ;
Loh, Po-Ru ;
Finucane, Hilary K. ;
Ripke, Stephan ;
Yang, Jian ;
Patterson, Nick ;
Daly, Mark J. ;
Price, Alkes L. ;
Neale, Benjamin M. .
NATURE GENETICS, 2015, 47 (03) :291-+
[10]   Sparse whole-genome sequencing identifies two loci for major depressive disorder [J].
Cai, Na ;
Bigdeli, Tim B. ;
Kretzschmar, Warren ;
Li, Yihan ;
Liang, Jieqin ;
Song, Li ;
Hu, Jingchu ;
Li, Qibin ;
Jin, Wei ;
Hu, Zhenfei ;
Wang, Guangbiao ;
Wang, Linmao ;
Qian, Puyi ;
Liu, Yuan ;
Jiang, Tao ;
Lu, Yao ;
Zhang, Xiuqing ;
Yin, Ye ;
Li, Yingrui ;
Xu, Xun ;
Gao, Jingfang ;
Reimers, Mark ;
Webb, Todd ;
Riley, Brien ;
Bacanu, Silviu ;
Peterson, Roseann E. ;
Chen, Yiping ;
Zhong, Hui ;
Liu, Zhengrong ;
Wang, Gang ;
Sun, Jing ;
Sang, Hong ;
Jiang, Guoqing ;
Zhou, Xiaoyan ;
Li, Yi ;
Li, Yi ;
Zhang, Wei ;
Wang, Xueyi ;
Fang, Xiang ;
Pan, Runde ;
Miao, Guodong ;
Zhang, Qiwen ;
Hu, Jian ;
Yu, Fengyu ;
Du, Bo ;
Sang, Wenhua ;
Li, Keqing ;
Chen, Guibing ;
Cai, Min ;
Yang, Lijun .
NATURE, 2015, 523 (7562) :588-+