Investigation of short tandem repeats in major depression using whole-genome sequencing data

Background: Major depressive disorder (MDD) is a leading contributor to global disease burden. Recent studies have shown that genetic factors play significant roles in the susceptibility to this condition; however, the underlying genetic basis currently remains largely unknown. Short tandem repeat (STR) has been proposed as an explanatory factor in the “missing heritability” of complex diseases or traits. Methods: We investigated STR variations from 15 MDD patients and 10 ethnically matched healthy controls based on their deep whole-genome sequencing (WGS) data. The lobSTR software was used to computationally determine STRs. Results: The results of the Mexican-American sample showed that STRs are significantly richer in healthy controls than in MDD cases on each of the 23 chromosomes (all false discovery rates, FDR P-values < 0.0062); while for the Australian of European-ancestry sample, there was no statistically significant STRs difference between MDD cases and controls. Limitations: High quality WGS costs limited obtaining larger datasets. Conclusions: This preliminary work is the first study that STR variations are applied to investigate MDD based on WGS data. The results on Mexican-American population may imply that within the same ancestry, targeted sequencing on a specific chromosome or region of genome would be sufficient for examining the relationship between STR and MDD. Further studies should examine larger sequencing datasets on other ethnic groups.