Citation:
Burkart KM, Sofer T, London SJ, Manichaikul A, Hartwig FP, Yan Q, Soler Artigas M, Avila L, Chen W, Davis Thomas S, Diaz AA, Hall IP, Horta BL, Kaplan RC, Laurie CC, Menezes AM, Morrison JV, Oelsner EC, Rastogi D, Rich SS, Soto-Quiros M, Stilp AM, Tobin MD, Wain LV, Celedón JC, Barr GR.
A Genome-Wide Association Study in Hispanics/Latinos Identifies Novel Signals for Lung Function. The Hispanic Community Health Study/Study of Latinos. Am J Respir Crit Care Med 2018;198(2):208-219.
Date Published:
2018 Jul 15Abstract:
RATIONALE: Lung function and chronic obstructive pulmonary disease (COPD) are heritable traits. Genome-wide association studies (GWAS) have identified numerous pulmonary function and COPD loci, primarily in cohorts of European ancestry.
OBJECTIVES: Perform a GWAS of COPD phenotypes in Hispanic/Latino populations to identify loci not previously detected in European populations.
METHODS: GWAS of lung function and COPD in Hispanic/Latino participants from a population-based cohort. We performed replication studies of novel loci in independent studies.
MEASUREMENTS AND MAIN RESULTS: Among 11,822 Hispanic/Latino participants, we identified eight novel signals; three replicated in independent populations of European Ancestry. A novel locus for FEV in ZSWIM7 (rs4791658; P = 4.99 × 10) replicated. A rare variant (minor allele frequency = 0.002) in HAL (rs145174011) was associated with FEV/FVC (P = 9.59 × 10) in a region previously identified for COPD-related phenotypes; it remained significant in conditional analyses but did not replicate. Admixture mapping identified a novel region, with a variant in AGMO (rs41331850), associated with Amerindian ancestry and FEV, which replicated. A novel locus for FEV identified among ever smokers (rs291231; P = 1.92 × 10) approached statistical significance for replication in admixed populations of African ancestry, and a novel SNP for COPD in PDZD2 (rs7709630; P = 1.56 × 10) regionally replicated. In addition, loci previously identified for lung function in European samples were associated in Hispanic/Latino participants in the Hispanic Community Health Study/Study of Latinos at the genome-wide significance level.
CONCLUSIONS: We identified novel signals for lung function and COPD in a Hispanic/Latino cohort. Including admixed populations when performing genetic studies may identify variants contributing to genetic etiologies of COPD.