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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.

TitleA Genome-Wide Association Study in Hispanics/Latinos Identifies Novel Signals for Lung Function. The Hispanic Community Health Study/Study of Latinos.
Publication TypePublication
Year2018
AuthorsBurkart KM, Sofer T, London SJ, Manichaikul A, Hartwig FP, Yan Q, Artigas MSoler, Avila L, Chen W, Thomas SDavis, 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, R Barr G
JournalAm J Respir Crit Care Med
Volume198
Issue2
Pagination208-219
Date Published2018 07 15
ISSN1535-4970
KeywordsAdolescent, Adult, Aged, Cohort Studies, Europe, European Continental Ancestry Group, Female, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, genome-wide association study, Hispanic Americans, Humans, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, Respiratory Function Tests, United States, Young Adult
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.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.

DOI10.1164/rccm.201707-1493OC
Alternate JournalAm J Respir Crit Care Med
PubMed ID29394082
PubMed Central IDPMC6058984
Grant ListR01 HL093081 / HL / NHLBI NIH HHS / United States
MR/N01104X/2 / MRC_ / Medical Research Council / United Kingdom
R35 HL135818 / HL / NHLBI NIH HHS / United States
MC_PC_12010 / MRC_ / Medical Research Council / United Kingdom
K01 HL118714 / HL / NHLBI NIH HHS / United States
N01 HC065237 / HC / NHLBI NIH HHS / United States
MR/N01104X/1 / MRC_ / Medical Research Council / United Kingdom
N01 HC065233 / HC / NHLBI NIH HHS / United States
N01 HC065236 / HC / NHLBI NIH HHS / United States
R01 DK101855 / DK / NIDDK NIH HHS / United States
K23 HL130627 / HL / NHLBI NIH HHS / United States
G1001799 / MRC_ / Medical Research Council / United Kingdom
UL1 TR000124 / TR / NCATS NIH HHS / United States
HHSN268201300005C / HL / NHLBI NIH HHS / United States
N01 HC065234 / HC / NHLBI NIH HHS / United States
R01 HL133137 / HL / NHLBI NIH HHS / United States
MR/N011317/1 / MRC_ / Medical Research Council / United Kingdom
K23 HL118733 / HL / NHLBI NIH HHS / United States
G1000861 / MRC_ / Medical Research Council / United Kingdom
UL1 TR001881 / TR / NCATS NIH HHS / United States
N01 HC065235 / HC / NHLBI NIH HHS / United States
R01 HL077612 / HL / NHLBI NIH HHS / United States
P30 ES009089 / ES / NIEHS NIH HHS / United States
MS#: 
0319
ECI: 
Manuscript Status: 
Published