Multiethnic meta-analysis identifies new loci for pulmonary function

Abstract

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N=60,552), African (N=8,429), Asian (N=9,959), and Hispanic/Latino (N=11,775) ethnicities. We identified over 50 novel loci at genome-wide significance in ancestry-specific and/or multiethnic meta-analyses. Recent fine mapping methods incorporating functional annotation, gene expression, and/or differences in linkage disequilibrium between ethnicities identified potential causal variants and genes at known and newly identified loci. Sixteen of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12.for use under a CC0 license.

New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries

“…Genetic variants associated with lung function and COPD susceptibility can provide etiological insights, assisting with risk prediction, as well as drug target identification and validation 6 . Whilst there has been considerable progress in identifying genetic markers associated with lung function and risk of COPD 4,7–19 seeking a high yield of associated genetic variants is key to progressing knowledge because: (i) implication of multiple molecules in each pathway will be needed to build an accurate picture of the pathways underpinning development of COPD; (ii) not all proteins identified will be druggable and; (iii) combining information across multiple variants can improve prediction of disease susceptibility.…”

New genetic signals for lung function highlight pathways and pleiotropy, and chronic obstructive pulmonary disease associations across multiple ancestries

“…Genetic variants associated with lung function and COPD susceptibility can be causally informative, assisting with risk prediction, as well as drug target identification and validation 6 . Whilst there has been considerable progress in identifying genetic markers associated with lung function and risk of COPD 4,7-19 seeking a high yield of associated genetic variants is key to progressing knowledge because: (i) implication of multiple molecules in each pathway will be needed to build an accurate picture of the pathways underpinning development of COPD; (ii) not all proteins identified will be druggable and; (iii) combining information across multiple variants can improve prediction of disease susceptibility.…”