title: A genome-wide association study of chronic obstructive pulmonary disease in Hispanics.
abstract: BACKGROUND
  Genome-wide association studies (GWAS) of chronic obstructive pulmonary disease (COPD) have identified disease-susceptibility loci, mostly in subjects of European descent.
  
  
  OBJECTIVE
  We hypothesized that by studying Hispanic populations we would be able to identify unique loci that contribute to COPD pathogenesis in Hispanics but remain undetected in GWAS of non-Hispanic populations.
  
  
  METHODS
  We conducted a metaanalysis of two GWAS of COPD in independent cohorts of Hispanics in Costa Rica and the United States (Multi-Ethnic Study of Atherosclerosis [MESA]). We performed a replication study of the top single-nucleotide polymorphisms in an independent Hispanic cohort in New Mexico (the Lovelace Smokers Cohort). We also attempted to replicate prior findings from genome-wide studies in non-Hispanic populations in Hispanic cohorts.
  
  
  RESULTS
  We found no genome-wide significant association with COPD in our metaanalysis of Costa Rica and MESA. After combining the top results from this metaanalysis with those from our replication study in the Lovelace Smokers Cohort, we identified two single-nucleotide polymorphisms approaching genome-wide significance for an association with COPD. The first (rs858249, combined P value = 6.1 × 10(-8)) is near the genes KLHL7 and NUPL2 on chromosome 7. The second (rs286499, combined P value = 8.4 × 10(-8)) is located in an intron of DLG2. The two most significant single-nucleotide polymorphisms in FAM13A from a previous genome-wide study in non-Hispanics were associated with COPD in Hispanics.
  
  
  CONCLUSIONS
  We have identified two novel loci (in or near the genes KLHL7/NUPL2 and DLG2) that may play a role in COPD pathogenesis in Hispanic populations.
authors.affiliation: 1 Division of Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: John M
authors.initials: JM
authors.lastname: Brehm
authors.forename: Ani
authors.initials: A
authors.lastname: Manichaikul
authors.forename: Michael H
authors.initials: MH
authors.lastname: Cho
authors.forename: Nadia
authors.initials: N
authors.lastname: Boutaoui
authors.forename: Qi
authors.initials: Q
authors.lastname: Yan
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Burkart
authors.forename: Paul L
authors.initials: PL
authors.lastname: Enright
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Hans
authors.initials: H
authors.lastname: Petersen
authors.forename: Shuguang
authors.initials: S
authors.lastname: Leng
authors.forename: Ma'en
authors.initials: M
authors.lastname: Obeidat
authors.forename: Yohan
authors.initials: Y
authors.lastname: Bossé
authors.forename: Corry-Anke
authors.initials: CA
authors.lastname: Brandsma
authors.forename: Ke
authors.initials: K
authors.lastname: Hao
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: Rhea
authors.initials: R
authors.lastname: Powell
authors.forename: Lydiana
authors.initials: L
authors.lastname: Avila
authors.forename: Manuel
authors.initials: M
authors.lastname: Soto-Quiros
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
authors.forename: Yohannes
authors.initials: Y
authors.lastname: Tesfaigzi
authors.forename: R Graham
authors.initials: RG
authors.lastname: Barr
authors.forename: Juan C
authors.initials: JC
authors.lastname: Celedón
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006630:Hispanic or Latino; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000208:ethnology* / Q000235:genetics / Q000503:physiopathology; D012189:Retrospective Studies; D014481:United States / Q000453:epidemiology; D055815:Young Adult
keywords: COPD; Hispanics; genome-wide association studies