Abstract
In order to determine the role of single nucleotide variants (SNVs) in modulating antidepressant response, we conducted a study, consisting of 929 major depressive disorder (MDD) patients, who were treated with antidepressant drugs (drug-only) or in combination with a repetitive transcranial magnetic stimulation (plus-rTMS), followed by targeted exome sequencing analysis. We found that the “plus-rTMS” patients presented a more effective response to the treatment when compared to the ‘drug-only’ group. Our data firstly demonstrated that the SNV burden had a significant impact on the antidepressant response presented in the “drug-only” group, but was limited in the “plus-rTMS” group. Further, after controlling for overall SNV burden, seven single nucleotide polymorphisms (SNPs) at five loci, IL1A, GNA15, PPP2CB, PLA2G4C, and GBA, were identified as affecting the antidepressant response at genome-wide significance (P < 5 × 10−08). Additional multiple variants achieved a level of correction for multiple testing, including GNA11, also shown as a strong signal for MDD risk. Our study showed some promising evidence on genetic variants that could be used as individualized therapeutic guides for MDD patients.
Highlights
Major depressive disorder (MDD) is one of the most common severe mental disorders with a 17.8% lifetime prevalence in global population[1]
Pharmacogenetic studies have indicated that genomic variations are one of the critical biological factors that prominently affect the individual differences of antidepressant response, in which common single nucleotide polymorphisms (SNPs) are estimated to explain 50% or more of the variation of the antidepressant response[9]
After controlling for the global single nucleotide variants (SNVs) burden, we examined the common SNPs for the antidepressant response
Summary
Major depressive disorder (MDD) is one of the most common severe mental disorders with a 17.8% lifetime prevalence in global population[1]. Current antidepressant drugs still have obvious shortcomings, including delayed onset, insufficient effectiveness, and low remission rates[2,3,4,5], which combined with a high prevalence have significantly exacerbated the disease to be the second leading cause of disability worldwide according to the 2020 Global Burden of Disease Study[6]. It is imperative in the study of antidepressant treatment to achieve a rapid improvement of depressive symptoms and to increase the recovery rate of the first episode of MDD7,8. A total of eight genome-wide association studies (GWAS)
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