Assessing the lack of diversity in genetics research across neurodegenerative diseases: A systematic review of the GWAS Catalog and literature.

The under-representation of non-European cohorts in neurodegenerative disease genome-wide association studies (GWAS) hampers precision medicine efforts. Despite the inherent genetic and phenotypic diversity in these diseases, GWAS research consistently exhibits a disproportionate emphasis on participants of European ancestry. This study reviews GWAS up to 2022, focusing on non-European or multi-ancestry neurodegeneration studies. We conducted a systematic review of GWAS results and publications up to 2022, focusing on non-European or multi-ancestry neurodegeneration studies. Rigorous article inclusion and quality assessment methods were employed. Of 123 neurodegenerative disease (NDD) GWAS reviewed, 82% predominantly featured European ancestry participants. A single European study identified over 90 risk loci, compared to a total of 50 novel loci in identified in all non-European or multi-ancestry studies. Notably, only six of the loci have been replicated. The significant under-representation of non-European ancestries in NDD GWAS hinders comprehensive genetic understanding. Prioritizing genomic diversity in future research is crucial for advancing NDD therapies and understanding. HIGHLIGHTS: Eighty-two percent of neurodegenerative genome-wide association studies (GWAS) focus on Europeans. Only 6 of 50 novel neurodegenerative disease (NDD) genetic loci have been replicated. Lack of diversity significantly hampers understanding of NDDs. Increasing diversity in NDD genetic research is urgently required. New initiatives are aiming to enhance diversity in NDD research.

Assessing the lack of diversity in genetics research across neurodegenerative diseases: a systematic review of the GWAS Catalog and literature.

Importance: The under-representation of participants with non-European ancestry in genome-wide association studies (GWAS) is a critical issue that has significant implications, including hindering the progress of precision medicine initiatives. This issue is particularly significant in the context of neurodegenerative diseases (NDDs), where current therapeutic approaches have shown limited success. Addressing this under-representation is crucial to harnessing the full potential of genomic medicine in underserved communities and improving outcomes for NDD patients. Objective: Our primary objective was to assess the representation of non-European ancestry participants in genetic discovery efforts related to NDDs. We aimed to quantify the extent of inclusion of diverse ancestry groups in NDD studies and determine the number of associated loci identified in more inclusive studies. Specifically, we sought to highlight the disparities in research efforts and outcomes between studies predominantly involving European ancestry participants and those deliberately targeting non-European or multi-ancestry populations across NDDs. Evidence Review: We conducted a systematic review utilizing existing GWAS results and publications to assess the inclusion of diverse ancestry groups in neurodegeneration and neurogenetics studies. Our search encompassed studies published up to the end of 2022, with a focus on identifying research that deliberately included non-European or multi-ancestry cohorts. We employed rigorous methods for the inclusion of identified articles and quality assessment. Findings: Our review identified a total of 123 NDD GWAS. Strikingly, 82% of these studies predominantly featured participants of European ancestry. Endeavors specifically targeting non-European or multi-ancestry populations across NDDs identified only 52 risk loci. This contrasts with predominantly European studies, which reported over 90 risk loci for a single disease. Encouragingly, over 65% of these discoveries occurred in 2020 or later, indicating a recent increase in studies deliberately including non-European cohorts. Conclusions and relevance: Our findings underscore the pressing need for increased diversity in neurodegenerative research. The significant under-representation of non-European ancestry participants in NDD GWAS limits our understanding of the genetic underpinnings of these diseases. To advance the field of neurodegenerative research and develop more effective therapies, it is imperative that future investigations prioritize and harness the genomic diversity present within and across global populations.

Multi-ancestry genome-wide association meta-analysis of Parkinson's disease.

Although over 90 independent risk variants have been identified for Parkinson's disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson's disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations.