Science · 2024 · 362 citations · 53 references
Life SciencesGeneticsMolecular GeneticsGenetic EpidemiologyGenomicsHuman GeneticsGenetic Fine-mappingGenetic RiskGenome-wide Association StudiesGenomic VariationGenotype-phenotype Association AnalysisGenotype-phenotype CorrelationCausal Effects Of Genetic VariantsFine-mapping Of Genetic AssociationsGenetic Architecture Of TraitsGenome-wide Association MappingGenome-wide Association Study Fine-mappingGenotype-phenotype AssociationsRisk Factors For DiseaseUnderrepresented Populations
One of the justifiable criticisms of human genetic studies is the underrepresentation of participants from diverse populations. Lack of inclusion must be addressed at-scale to identify causal disease factors and understand the genetic causes of health disparities. We present genome-wide associations for 2068 traits from 635,969 participants in the Department of Veterans Affairs Million Veteran Program, a longitudinal study of diverse United States Veterans. Systematic analysis revealed 13,672 genomic risk loci; 1608 were only significant after including non-European populations. Fine-mapping identified causal variants at 6318 signals across 613 traits. One-third ( n = 2069) were identified in participants from non-European populations. This reveals a broadly similar genetic architecture across populations, highlights genetic insights gained from underrepresented groups, and presents an extensive atlas of genetic associations.
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