Effective in treatment-resistant depression (TRD), repetitive transcranial magnetic stimulation (rTMS) presents a remission rate between 30% and 40%. Although genetics could be one potential source of inter-individual variability in rTMS responsiveness, few studies have sought to identify possible genetic basis of rTMS response [1,2]. Therefore, we used an extreme-phenotype design in which we compared genome-wide allelic variation between rigorously defined rTMS responders and non-responders.A total of 99 TRD patients provided informed consent and this study was approved by the Human Research and Ethics Committee of the Alfred Hospital. All were submitted to a rTMS protocol and completed at least 18 sessions of 10 Hz at left dorsolateral prefrontal cortex (DLPFC). Clinical outcomes (responder or non-responder) were determined based on scores on the Montgomery Asberg Depression Rating Scale (MADRS).We used the extreme-phenotype design. Patients were separated into two groups, responders -patients with at least 60% reduction on the MADRS scale (n ¼ 29) and non-responders -patients with 10% or less reduction on the MADRS scale (n ¼ 19). We used this criteria considering that extreme scoring patients (<10 >60) may present more representative genetic results, improving power to detect phenotype-genotype associations [3,4].Genotyping was performed using the Infinium PsychArray-24 BeadChip (Illumina, Inc., San Diego, CA, USA) and analyzed with PLINK 1.9. We performed quality control to remove individuals or markers with high error rates. Data quality control parameters were: call rate (GENO) > 90%, maximum individual missingness rate (MIND) < 10%, minor allele frequency (MAF) > 5% and Hardy-Weinberg equilibrium (HWE) p-value > 10e6. We performed standard association analysis to compare allele frequency in both groups with a 95% CI. After identifying the significant SNPs and genes a functional enrichment analysis using STRING and Cytoscape databases was performed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.