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Investigation of short tandem repeats in major depression using whole-genome sequencing data
Chenglong Yu1, Bernhard T Baune2, Ma-Li Wong3
1Robinson Research Institute, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia; Mind and Brain Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia; School of Medicine, Faculty of Medicine, Nursing and Health Sciences, Flinders University, Bedford Park, SA 5042, Australia.
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.
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