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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.

Authors :
Burkart, Kristin M
Sofer, Tamar
London, Stephanie J
Manichaikul, Ani
Hartwig, Fernando P
Yan, Qi
Soler Artigas, María
Avila, Lydiana
Chen, Wei
Davis Thomas, Sonia
Diaz, Alejandro A
Hall, Ian P
Horta, Bernardo L
Kaplan, Robert C
Laurie, Cathy C
Menezes, Ana M
Morrison, Jean V
Oelsner, Elizabeth C
Rastogi, Deepa
Rich, Stephen S
Source :
American Journal of Respiratory & Critical Care Medicine; 7/15/2018, Vol. 198 Issue 2, p208-219, 12p
Publication Year :
2018

Abstract

<bold>Rationale: </bold>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.<bold>Objectives: </bold>Perform a GWAS of COPD phenotypes in Hispanic/Latino populations to identify loci not previously detected in European populations.<bold>Methods: </bold>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.<bold>Measurements and Main Results: </bold>Among 11,822 Hispanic/Latino participants, we identified eight novel signals; three replicated in independent populations of European Ancestry. A novel locus for FEV1 in ZSWIM7 (rs4791658; P = 4.99 × 10-9) replicated. A rare variant (minor allele frequency = 0.002) in HAL (rs145174011) was associated with FEV1/FVC (P = 9.59 × 10-9) 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 FEV1, which replicated. A novel locus for FEV1 identified among ever smokers (rs291231; P = 1.92 × 10-8) approached statistical significance for replication in admixed populations of African ancestry, and a novel SNP for COPD in PDZD2 (rs7709630; P = 1.56 × 10-8) 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.<bold>Conclusions: </bold>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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
1073449X
Volume :
198
Issue :
2
Database :
Complementary Index
Journal :
American Journal of Respiratory & Critical Care Medicine
Publication Type :
Academic Journal
Accession number :
130697238
Full Text :
https://doi.org/10.1164/rccm.201707-1493OC