Inherited burden for disease predisposition in diverse populations

TL;DR

This study explores inherited genetic variants linked to disease risk in diverse populations, showing how personalized medicine could help prevent disease and improve health.

Contribution

The study expands the catalog of pathogenic and likely pathogenic variants by nearly six-fold using multiple genomic datasets.

Findings

On average, individuals are born with 4.70 pathogenic or likely pathogenic variants.

1 in 11 individuals has an actionable genotype for potential disease prevention.

382 genes are identified as candidates for carrier screening.

Abstract

We leveraged allele frequencies from gnomAD, Regeneron Genetics Center Million Exome and Turkish Variome for 4591 disease genes from PanelApp and OMIM, and identified 97,135 pathogenic and 478,263 likely pathogenic variants using an American College of Medical Genetics and Genomics-based classifier. This expanded pathogenic and likely pathogenic variants nearly six-fold. On average, an individual is born with 4.70 pathogenic or likely pathogenic variants, of which 1.66 are compatible with a Mendelian condition at the genotype level; 1 in 11 has an actionable genotype, and 382 genes are candidates for carrier screening. A genome-first approach revealed the likelihood of having a genotype compatible with disease in 13 ICD-10 disease groups, for example, congenital (1 in 2.70), musculoskeletal/connective (1 in 3.00) and blood/immune (1 in 3.07 individuals). Evidence-based genetic epidemiology demonstrates the potential of personalized medicine for the implementation of early preventive measures and incentivization of lifestyle changes to enhance healthspan and lifespan.

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