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

Patricia C Swart; Leigh L van den Heuvel; Cathryn M Lewis; Soraya Seedat; Sian M J Hemmings

doi:10.3389/fnins.2021.677800

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

Front Neurosci. 2021 Jun 10:15:677800. doi: 10.3389/fnins.2021.677800. eCollection 2021.

Authors

Patricia C Swart^{1

2}, Leigh L van den Heuvel^{1

2}, Cathryn M Lewis³, Soraya Seedat^{1

2}, Sian M J Hemmings^{1

2}

Affiliations

¹ Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
² South African Medical Research Council, Stellenbosch University Genomics of Brain Disorders Research Unit, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
³ Social, Genetic and Developmental Psychiatry Centre, King's College London, London, United Kingdom.

Abstract

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 (n = 260) and controls (n = 343) revealed no SNPs of genome-wide significance. However, several independent loci, as well as five SNPs in the PARK2 gene, were suggestively associated with PTSD (p < 5 × 10^-6). PTSD-PRS was associated with PTSD diagnosis (Nagelkerke's pseudo R ² = 0.0131, p = 0.00786), PTSD symptom severity [as measured by CAPS-5 total score (R ² = 0.00856, p = 0.0367) and PCL-5 score (R ² = 0.00737, p = 0.0353)], and MetS (Nagelkerke's pseudo R ² = 0.00969, p = 0.0217). These findings suggest an association between PTSD and PARK2, 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.

Keywords: GWAS; PARK2; PTSD; metabolic syndrome; polygenic risk scores.