What have we learned from genome-wide association studies (GWAS) in Parkinson's disease?

Abstract

After fifteen years of genome-wide association studies (GWAS) in Parkinson's disease (PD), what have we learned? Addressing this question will help catalogue the progress made towards elucidating disease mechanisms, improving the clinical utility of the identified loci, and envisioning how we can harness the strides to develop translational GWAS strategies. Here we review the advances of PD GWAS made to date while critically addressing the challenges and opportunities for next-generation GWAS. Thus, deciphering the missing heritability in underrepresented populations is currently at the reach of hand for a truly comprehensive understanding of the genetics of PD across the different ethnicities. Moreover, state-of-the-art GWAS designs hold a true potential for enhancing the clinical applicability of genetic findings, for instance, by improving disease prediction (PD risk and progression). Lastly, advanced PD GWAS findings, alone or in combination with clinical and environmental parameters, are expected to have the capacity for defining patient enriched cohorts stratified by genetic risk profiles and readily available for neuroprotective clinical trials. Overall, envisioning future strategies for advanced GWAS is currently timely and can be instrumental in providing novel genetic readouts essential for a true clinical translatability of PD genetic findings.