Genetic analyses of diverse populations improves discovery for complex traits

Abstract

Genome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development and clinical guidelines. However, the majority of discovery efforts are based on data from populations of European ancestry 1-3. In light of the differential genetic architecture that is known to exist between populations, bias in representation can exacerbate existing disease and healthcare disparities. Critical variants may be missed if they have a low frequency or are completely absent in European populations, especially as the field shifts its attention towards rare variants, which are more likely to be population-specific 4-10. Additionally, effect sizes and their derived risk prediction scores derived in one population may Reprints and permissions information is available at http://www.nature.com/reprints.

Rapid detection of identity-by-descent tracts for mega-scale datasets

“…A total of 51,520 subjects were genotyped on the MEGA array as part of the Population Architecture using Genomics and Epidemiology (PAGE) study, and subsequently underwent quality control filters as described in Wojcik et al 34 . Genotypes that passed quality control (n=1,402,653) underwent phasing using SHAPEIT2.…”

Subthreshold psychosis symptoms associated with molecular genetic risk in a population-based cohort: Findings from Generation Scotland

“…It bears mentioning that with current methods, examination of diverse risk groups enhances GWAS discovery and increases generalizability. [51][52][53]…”

Introduction: The state of minority and health disparities in research and practice in genetic counseling and genomic medicine

“…has long been recognized as a contributing factor to the persistent inequitable benefits of genetic testing (Neben et al, 2019;Popejoy et al, 2018;Wojcik et al, 2019) Our hope is that this Special Issue will inspire and motivate genetic counselors and other healthcare professionals to seize this moment and momentum as a turning point toward equity, and personal and professional multicultural competence. Inevitably, genetic counselors who commit to multicultural agency will face rewards and challenges.…”

“…Insufficient inclusion of diverse populations in genomic research has long been recognized as a contributing factor to the persistent inequitable benefits of genetic testing (Neben et al, 2019; Popejoy et al, 2018; Wojcik et al, 2019). Besides limited access, Roberts et al show that genetic test result interpretations and accurate risk assessments remain a challenge when rates of pathogenic variant and variant of unknown significance vary among different ancestral populations.…”