A genome-wide association study identifies distinct variants associated with pulmonary function among European and African ancestries from the UK Biobank

Abstract

Pulmonary function is an indicator of well-being, and pulmonary pathologies are the third major cause of death worldwide. We analysed the UK Biobank genome-wide association summary statistics of pulmonary function for Europeans and individuals of recent African descent to identify variants associated with the trait in the two ancestries. Here, we show 627 variants in Europeans and 3 in Africans associated with three pulmonary function parameters. In addition to the 110 variants in Europeans previously reported to be associated with phenotypes related to pulmonary function, we identify 279 novel loci, including an ISX intergenic variant rs369476290 on chromosome 22 in Africans. Remarkably, we find no shared variants among Africans and Europeans. Furthermore, enrichment analyses of variants separately for each ancestry background reveal significant enrichment for terms related to pulmonary phenotypes in Europeans but not Africans. Further analysis of studies of pulmonary phenotypes reveals that individuals of European background are disproportionally overrepresented in datasets compared to Africans, with the gap widening over the past five years. Our findings extend our understanding of the different variants that modify the pulmonary function in Africans and Europeans, a promising finding for future GWASs and medical studies.

Multitrait Genome-Wide Analysis in the UK Biobank Reveals Novel and Distinct Variants Influencing Cardiovascular Traits in Africans and Europeans

“…These discoveries highlight the genetic diversity underlying traits and emphasize the importance of more diverse and inclusive genomic research. Previous literature has noted that a disproportionate focus on European-ancestry populations in genetic studies has limited our understanding of disease genetics across diverse populations 18 . Importantly, our findings caution against the uncritical application of genetic risk prediction models across populations, emphasizing the need for population-specific genetic research in precision medicine 62 .…”

“…Despite bearing the highest hypertension burden, the African population remains comparatively under-explored in GWAS 13,14 . Emerging large-scale GWAS and metaanalyses are beginning to shed light on the genetic underpinnings of this complex condition within this and other populations [15][16][17][18] . However, few extensive studies have concurrently examined the genetic and social health determinants, despite compelling evidence substantiating their contribution to hypertension 12 .…”

Unveiling the role of Tdark genes in genetic diseases and phenotypes through bioinformatics-based functional enrichment and network analyses

“…Recent advances in genomic sequencing technology have led to the discovery of thousands of genetic variants and genes associated with genetic diseases and phenotypes [15–17]. The implementation of high throughput next-generation sequencing techniques has enabled the swift sequencing of a vast number of complete genomes, resulting in an ever-growing wealth of genomic information that is becoming increasingly accessible [18–21].…”

Adam19 Deficiency Impacts Pulmonary Function: Human GWAS Follow-up in Mouse

“…Human genome-wide association studies (GWAS) have identi ed genetic variants in over 550 genes related to pulmonary function [2]. Among these, variants in a disintegrin and metalloproteinase domain 19 (ADAM19) have been consistently associated with forced expiratory volume in the rst second (FEV 1 ) [3,4], the ratio of FEV 1 to forced vital capacity (FVC) [1][2][3][5][6][7][8], peak expiratory ow (PEF) [3,4], and COPD [9,10]. However, while GWAS is powerful for identifying genetic associations, it cannot assign causality.…”