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

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