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A Genome-Wide Association Study in Hispanics/Latinos Identifies Novel Signals for Lung Function. The Hispanic Community Health Study/Study of Latinos.
- Source :
-
American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2018 Jul 15; Vol. 198 (2), pp. 208-219. - Publication Year :
- 2018
-
Abstract
- 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.<br />Objectives: Perform a GWAS of COPD phenotypes in Hispanic/Latino populations to identify loci not previously detected in European populations.<br />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.<br />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 <subscript>1</subscript> in ZSWIM7 (rs4791658; P = 4.99 × 10 <superscript>-9</superscript> ) replicated. A rare variant (minor allele frequency = 0.002) in HAL (rs145174011) was associated with FEV <subscript>1</subscript> /FVC (P = 9.59 × 10 <superscript>-9</superscript> ) 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 <subscript>1</subscript> , which replicated. A novel locus for FEV <subscript>1</subscript> identified among ever smokers (rs291231; P = 1.92 × 10 <superscript>-8</superscript> ) approached statistical significance for replication in admixed populations of African ancestry, and a novel SNP for COPD in PDZD2 (rs7709630; P = 1.56 × 10 <superscript>-8</superscript> ) 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.<br />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.
- Subjects :
- Adolescent
Adult
Aged
Cohort Studies
Europe
Female
Gene Frequency
Genetic Loci
Humans
Male
Middle Aged
Respiratory Function Tests
United States
Young Adult
Genetic Predisposition to Disease
Genome-Wide Association Study
Hispanic or Latino genetics
Pulmonary Disease, Chronic Obstructive genetics
White People genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1535-4970
- Volume :
- 198
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- American journal of respiratory and critical care medicine
- Publication Type :
- Academic Journal
- Accession number :
- 29394082
- Full Text :
- https://doi.org/10.1164/rccm.201707-1493OC