A genome-wide association study in hispanics/latinos identifies novel signals for lung function the hispanic community health study/study of latinos

Kristin M. Burkart, Tamar Sofer, Stephanie J. London, Ani Manichaikul, Fernando P. Hartwig, Qi Yan, María Soler Artigas, Lydiana Avila, Wei Chen, Sonia Davis Thomas, Alejandro A. Diaz, Ian P. Hall, Bernardo L. Horta, Robert C. Kaplan, Cathy C. Laurie, Ana M. Menezes, Jean V. Morrison, Elizabeth C. Oelsner, Deepa Rastogi, Stephen S. RichManuel Soto-Quiros, Adrienne M. Stilp, Martin D. Tobin, Louise V. Wain, Juan C. Celedón, R. Graham Barr

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)208-219
Number of pages12
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume198
Issue number2
DOIs
StatePublished - Jul 15 2018

Fingerprint

Genome-Wide Association Study
Hispanic Americans
Lung
Chronic Obstructive Pulmonary Disease
Health
Population
Phenotype
Gene Frequency
Single Nucleotide Polymorphism
Genome

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 journalArticle

Burkart, KM, Sofer, T, London, SJ, Manichaikul, A, Hartwig, FP, Yan, Q, Artigas, MS, Avila, L, Chen, W, Thomas, SD, 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 & Graham Barr, R 2018, 'A genome-wide association study in hispanics/latinos identifies novel signals for lung function the hispanic community health study/study of latinos', American Journal of Respiratory and Critical Care Medicine, vol. 198, no. 2, pp. 208-219. https://doi.org/10.1164/rccm.201707-1493OC
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. / A genome-wide association study in hispanics/latinos identifies novel signals for lung function the hispanic community health study/study of latinos. In: American Journal of Respiratory and Critical Care Medicine. 2018 ; Vol. 198, No. 2. pp. 208-219.
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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.",
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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.

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KW - Chronic bstructive pulmonary disease

KW - Genome-wide association study

KW - Hispanic/Latino

KW - Ingle-nucleotide polymorphisms

KW - Lung function

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