AUTHOR=Swart Patricia C. , van den Heuvel Leigh L. , Lewis Cathryn M. , Seedat Soraya , Hemmings Sian M. J. 

TITLE=A Genome-Wide Association Study and Polygenic Risk Score Analysis of Posttraumatic Stress Disorder and Metabolic Syndrome in a South African Population

JOURNAL=Frontiers in Neuroscience

VOLUME=15

YEAR=2021

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2021.677800

DOI=10.3389/fnins.2021.677800

ISSN=1662-453X

ABSTRACT=<p>Posttraumatic stress disorder (PTSD) is a trauma-related disorder that frequently co-occurs with metabolic syndrome (MetS). MetS is characterized by obesity, dyslipidemia, and insulin resistance. To provide insight into these co-morbidities, we performed a genome-wide association study (GWAS) meta-analysis to identify genetic variants associated with PTSD, and determined if PTSD polygenic risk scores (PRS) could predict PTSD and MetS in a South African mixed-ancestry sample. The GWAS meta-analysis of PTSD participants (<italic>n</italic> = 260) and controls (<italic>n</italic> = 343) revealed no SNPs of genome-wide significance. However, several independent loci, as well as five SNPs in the <italic>PARK2</italic> gene, were suggestively associated with PTSD (<italic>p</italic> &lt; 5 × 10<sup>–6</sup>). PTSD-PRS was associated with PTSD diagnosis (Nagelkerke’s pseudo <italic>R</italic><sup>2</sup> = 0.0131, <italic>p</italic> = 0.00786), PTSD symptom severity [as measured by CAPS-5 total score (<italic>R</italic><sup>2</sup> = 0.00856, <italic>p</italic> = 0.0367) and PCL-5 score (<italic>R</italic><sup>2</sup> = 0.00737, <italic>p</italic> = 0.0353)], and MetS (Nagelkerke’s pseudo <italic>R</italic><sup>2</sup> = 0.00969, <italic>p</italic> = 0.0217). These findings suggest an association between PTSD and <italic>PARK2</italic>, corresponding with results from the largest PTSD-GWAS conducted to date. PRS analysis suggests that genetic variants associated with PTSD are also involved in the development of MetS. Overall, the results contribute to a broader goal of increasing diversity in psychiatric genetics.</p>