Genome-wide association studies of antidepressant class response and treatment-resistant depression

被引：41

作者：

Li, Qingqin S. ^{[1
]}

Tian, Chao ^{[2
]}

Hinds, David ^{[2
]}

机构：

[1] Janssen Res & Dev LLC, Titusville, NJ 08560 USA

[2] 23andMe Inc, Sunnyvale, CA USA

来源：

TRANSLATIONAL PSYCHIATRY | 2020年 / 10卷 / 01期

关键词：

GENE-EXPRESSION; PHARMACOGENETICS; DISORDER;

D O I：

10.1038/s41398-020-01035-6

中图分类号：

R749 [精神病学];

学科分类号：

100205 ;

摘要：

The "antidepressant efficacy" survey (AES) was deployed to > 50,000 23andMe, Inc. research participants to investigate the genetic basis of treatment-resistant depression (TRD) and non-treatment-resistant depression (NTRD). Genome-wide association studies (GWAS) were performed, including TRD vs. NTRD, selective serotonin reuptake inhibitor (SSRI) responders vs. non-responders, serotonin-norepinephrine reuptake inhibitor (SNRI) responders vs. non-responders, and norepinephrine-dopamine reuptake inhibitor responders vs. non-responders. Only the SSRI association reached the genome-wide significance threshold (p < 5 x 10(-8)): one genomic region in RNF219-AS1 (SNP rs4884091, p = 2.42 x 10(-8), OR = 1.21); this association was also observed in the meta-analysis (13,130 responders vs. 6,610 non-responders) of AES and an earlier "antidepressant efficacy and side effects" survey (AESES) cohort. Meta-analysis for SNRI response phenotype derived from AES and AESES (4030 responders vs. 3049 non-responders) identified another genomic region (lead SNP rs4955665, p = 1.62 x 10(-9), OR = 1.25) in an intronic region of MECOM passing the genome-wide significance threshold. Meta-analysis for the TRD phenotype (31,068 NTRD vs 5,714 TRD) identified one additional genomic region (lead SNP rs150245813, p = 8.07 x 10(-9), OR = 0.80) in 10p11.1 passing the genome-wide significance threshold. A stronger association for rs150245813 was observed in current study (p = 7.35 x 10(-7), OR = 0.79) than the previous study (p = 1.40 x 10(-3), OR = 0.81), and for rs4955665, a stronger association in previous study (p = 1.21 x 10(-6), OR = 1.27) than the current study (p = 2.64 x 10(-4), OR = 1.21). In total, three novel loci associated with SSRI or SNRI (responders vs. non-responders), and NTRD vs TRD were identified; gene level association and gene set enrichment analyses implicate enrichment of genes involved in immune process.

引用

页数：12

共 48 条

[11] Novel Associations for Hypothyroidism Include Known Autoimmune Risk Loci [J].

Eriksson, Nicholas ;

Tung, Joyce Y. ;

Kiefer, Amy K. ;

Hinds, David A. ;

Francke, Uta ;

Mountain, Joanna L. ;

Do, Chuong B. .

PLOS ONE, 2012, 7 (04)

[12] Web-Based, Participant-Driven Studies Yield Novel Genetic Associations for Common Traits [J].

Eriksson, Nicholas ;

Macpherson, J. Michael ;

Tung, Joyce Y. ;

Hon, Lawrence S. ;

Naughton, Brian ;

Saxonov, Serge ;

Avey, Linda ;

Wojcicki, Anne ;

Pe'er, Itsik ;

Mountain, Joanna .

PLOS GENETICS, 2010, 6 (06) :1-20

[13]

Ethical & Independent Review Services, 2015, I REV BOARD

[14] New insights into the pharmacogenomics of antidepressant response from the GENDEP and STAR*D studies: rare variant analysis and high-density imputation [J].

Fabbri, C. ;

Tansey, K. E. ;

Perlis, R. H. ;

Hauser, J. ;

Henigsberg, N. ;

Maier, W. ;

Mors, O. ;

Placentino, A. ;

Rietschel, M. ;

Souery, D. ;

Breen, G. ;

Curtis, C. ;

Sang-Hyuk, L. ;

Newhouse, S. ;

Patel, H. ;

Guipponi, M. ;

Perroud, N. ;

Bondolfi, G. ;

O'Donovan, M. ;

Lewis, G. ;

Biernacka, J. M. ;

Weinshilboum, R. M. ;

Farmer, A. ;

Aitchison, K. J. ;

Craig, I ;

McGuffin, P. ;

Uher, R. ;

Lewis, C. M. .

PHARMACOGENOMICS JOURNAL, 2018, 18 (03) :413-421

[15] Diagnosis and definition of treatment-resistant depression [J].

Fava, M .

BIOLOGICAL PSYCHIATRY, 2003, 53 (08) :649-659

[16] Gene expression elucidates functional impact of polygenic risk for schizophrenia [J].

Fromer, Menachem ;

Roussos, Panos ;

Sieberts, Solveig K. ;

Johnson, Jessica S. ;

Kavanagh, David H. ;

Perumal, Thanneer M. ;

Ruderfer, Douglas M. ;

Oh, Edwin C. ;

Topol, Aaron ;

Shah, Hardik R. ;

Klei, Lambertus L. ;

Kramer, Robin ;

Pinto, Dalila ;

Gumus, Zeynep H. ;

Cicek, A. Ercument ;

Dang, Kristen K. ;

Browne, Andrew ;

Lu, Cong ;

Xie, Lu ;

Readhead, Ben ;

Stahl, Eli A. ;

Xiao, Jianqiu ;

Parvizi, Mahsa ;

Hamamsy, Tymor ;

Fullard, John F. ;

Wang, Ying-Chih ;

Mahajan, Milind C. ;

Derry, Jonathan M. J. ;

Dudley, Joel T. ;

Hemby, Scott E. ;

Logsdon, Benjamin A. ;

Talbot, Konrad ;

Raj, Towfique ;

Bennett, David A. ;

De Jager, Philip L. ;

Zhu, Jun ;

Zhang, Bin ;

Sullivan, Patrick F. ;

Chess, Andrew ;

Purcell, Shaun M. ;

Shinobu, Leslie A. ;

Mangravite, Lara M. ;

Toyoshiba, Hiroyoshi ;

Gur, Raquel E. ;

Hahn, Chang-Gyu ;

Lewis, David A. ;

Haroutunian, Vahram ;

Peters, Mette A. ;

Lipska, Barbara K. ;

Buxbaum, Joseph D. .

NATURE NEUROSCIENCE, 2016, 19 (11) :1442-1453

[17] Pharmacogenetics of antidepressant response: A polygenic approach [J].

Garcia-Gonzalez, Judit ;

Tansey, Katherine E. ;

Hauser, Joanna ;

Henigsberg, Neven ;

Maier, Wolfgang ;

Mors, Ole ;

Placentino, Anna ;

Rietschel, Marcella ;

Souery, Daniel ;

Zagar, Tina ;

Czerski, Piotr M. ;

Jerman, Borut ;

Buttenschon, Henriette N. ;

Schulze, Thomas G. ;

Zobel, Astrid ;

Farmer, Anne ;

Aitchison, Katherine J. ;

Craig, Ian ;

McGuffin, Peter ;

Giupponi, Michel ;

Perroud, Nader ;

Bondolfi, Guido ;

Evans, David ;

O'Donovan, Michael ;

Peters, Tim J. ;

Wendland, Jens R. ;

Lewis, Glyn ;

Kapur, Shitij ;

Perlis, Roy ;

Arolt, Volker ;

Domschke, Katharina ;

Breen, Gerome ;

Curtis, Charles ;

Sang-Hyuk, Lee ;

Kan, Carol ;

Newhouse, Stephen ;

Patel, Hamel ;

Baune, Bernhard T. ;

Uher, Rudolf ;

Lewis, Cathryn M. ;

Fabbri, Chiara .

PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 2017, 75 :128-134

[18] A Genomewide Association Study of Citalopram Response in Major Depressive Disorder [J].

Garriock, Holly A. ;

Kraft, Jeffrey B. ;

Shyn, Stanley I. ;

Peters, Eric J. ;

Yokoyama, Jennifer S. ;

Jenkins, Gregory D. ;

Reinalda, Megan S. ;

Slager, Susan L. ;

McGrath, Patrick J. ;

Hamilton, Steven P. .

BIOLOGICAL PSYCHIATRY, 2010, 67 (02) :133-138

[19]

Gilly A, 2018, METAANALYSIS QUANTIT

[20]

Hodge RebeccaD., 2019, Nature, P384826

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