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 FEV1 in ZSWIM7 (rs4791658; P = 4.99 3 1029) replicated. A rare variant (minor allele frequency = 0.002) in HAL (rs145174011) was associated with FEV1/FVC (P = 9.59 3 1029) 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 3 1028) approached statistical significance for replication in admixed populations of African ancestry, and a novel SNP for COPD in PDZD2 (rs7709630; P = 1.56 3 1028) 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 208-219 |
| Number of pages | 12 |
| Journal | American Journal of Respiratory and Critical Care Medicine |
| Volume | 198 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jul 15 2018 |
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Keywords
- Chronic bstructive pulmonary disease
- Genome-wide association study
- Hispanic/Latino
- Ingle-nucleotide polymorphisms
- Lung function
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Critical Care and Intensive Care Medicine
Cite this
A genome-wide association study in hispanics/latinos identifies novel signals for lung function the hispanic community health study/study of latinos. / Burkart, Kristin M.; Sofer, Tamar; London, Stephanie J.; Manichaikul, Ani; Hartwig, Fernando P.; Yan, Qi; Artigas, María Soler; Avila, Lydiana; Chen, Wei; Thomas, Sonia Davis; 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.; Soto-Quiros, Manuel; Stilp, Adrienne M.; Tobin, Martin D.; Wain, Louise V.; Celedón, Juan C.; Graham Barr, R.
In: American Journal of Respiratory and Critical Care Medicine, Vol. 198, No. 2, 15.07.2018, p. 208-219.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A genome-wide association study in hispanics/latinos identifies novel signals for lung function the hispanic community health study/study of latinos
AU - Burkart, Kristin M.
AU - Sofer, Tamar
AU - London, Stephanie J.
AU - Manichaikul, Ani
AU - Hartwig, Fernando P.
AU - Yan, Qi
AU - Artigas, María Soler
AU - Avila, Lydiana
AU - Chen, Wei
AU - Thomas, Sonia Davis
AU - Diaz, Alejandro A.
AU - Hall, Ian P.
AU - Horta, Bernardo L.
AU - Kaplan, Robert C.
AU - Laurie, Cathy C.
AU - Menezes, Ana M.
AU - Morrison, Jean V.
AU - Oelsner, Elizabeth C.
AU - Rastogi, Deepa
AU - Rich, Stephen S.
AU - Soto-Quiros, Manuel
AU - Stilp, Adrienne M.
AU - Tobin, Martin D.
AU - Wain, Louise V.
AU - Celedón, Juan C.
AU - Graham Barr, R.
PY - 2018/7/15
Y1 - 2018/7/15
N2 - 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 FEV1 in ZSWIM7 (rs4791658; P = 4.99 3 1029) replicated. A rare variant (minor allele frequency = 0.002) in HAL (rs145174011) was associated with FEV1/FVC (P = 9.59 3 1029) 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 3 1028) approached statistical significance for replication in admixed populations of African ancestry, and a novel SNP for COPD in PDZD2 (rs7709630; P = 1.56 3 1028) 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.
AB - 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 FEV1 in ZSWIM7 (rs4791658; P = 4.99 3 1029) replicated. A rare variant (minor allele frequency = 0.002) in HAL (rs145174011) was associated with FEV1/FVC (P = 9.59 3 1029) 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 3 1028) approached statistical significance for replication in admixed populations of African ancestry, and a novel SNP for COPD in PDZD2 (rs7709630; P = 1.56 3 1028) 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.
KW - Chronic bstructive pulmonary disease
KW - Genome-wide association study
KW - Hispanic/Latino
KW - Ingle-nucleotide polymorphisms
KW - Lung function
UR - http://www.scopus.com/inward/record.url?scp=85050092827&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85050092827&partnerID=8YFLogxK
U2 - 10.1164/rccm.201707-1493OC
DO - 10.1164/rccm.201707-1493OC
M3 - Article
C2 - 29394082
AN - SCOPUS:85050092827
VL - 198
SP - 208
EP - 219
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
SN - 1073-449X
IS - 2
ER -