title: A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13.
abstract: The genetic risk factors for chronic obstructive pulmonary disease (COPD) are still largely unknown. To date, genome-wide association studies (GWASs) of limited size have identified several novel risk loci for COPD at CHRNA3/CHRNA5/IREB2, HHIP and FAM13A; additional loci may be identified through larger studies. We performed a GWAS using a total of 3499 cases and 1922 control subjects from four cohorts: the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); the Normative Aging Study (NAS) and National Emphysema Treatment Trial (NETT); Bergen, Norway (GenKOLS); and the COPDGene study. Genotyping was performed on Illumina platforms with additional markers imputed using 1000 Genomes data; results were summarized using fixed-effect meta-analysis. We identified a new genome-wide significant locus on chromosome 19q13 (rs7937, OR = 0.74, P = 2.9 × 10(-9)). Genotyping this single nucleotide polymorphism (SNP) and another nearby SNP in linkage disequilibrium (rs2604894) in 2859 subjects from the family-based International COPD Genetics Network study (ICGN) demonstrated supportive evidence for association for COPD (P = 0.28 and 0.11 for rs7937 and rs2604894), pre-bronchodilator FEV(1) (P = 0.08 and 0.04) and severe (GOLD 3&4) COPD (P = 0.09 and 0.017). This region includes RAB4B, EGLN2, MIA and CYP2A6, and has previously been identified in association with cigarette smoking behavior.
authors.affiliation: Channing Laboratory, Brigham & Women’s Hospital, Boston, MA 02115, USA. michael.cho@channing.harvard.edu
authors.forename: Michael H
authors.initials: MH
authors.lastname: Cho
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Castaldi
authors.forename: Emily S
authors.initials: ES
authors.lastname: Wan
authors.forename: Mateusz
authors.initials: M
authors.lastname: Siedlinski
authors.forename: Craig P
authors.initials: CP
authors.lastname: Hersh
authors.forename: Dawn L
authors.initials: DL
authors.lastname: Demeo
authors.forename: Blanca E
authors.initials: BE
authors.lastname: Himes
authors.forename: Jody S
authors.initials: JS
authors.lastname: Sylvia
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Klanderman
authors.forename: John P
authors.initials: JP
authors.lastname: Ziniti
authors.forename: Christoph
authors.initials: C
authors.lastname: Lange
authors.forename: Augusto A
authors.initials: AA
authors.lastname: Litonjua
authors.forename: David
authors.initials: D
authors.lastname: Sparrow
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Regan
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Make
authors.forename: John E
authors.initials: JE
authors.lastname: Hokanson
authors.forename: Tanda
authors.initials: T
authors.lastname: Murray
authors.forename: Jacqueline B
authors.initials: JB
authors.lastname: Hetmanski
authors.forename: Sreekumar G
authors.initials: SG
authors.lastname: Pillai
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Kong
authors.forename: Wayne H
authors.initials: WH
authors.lastname: Anderson
authors.forename: Ruth
authors.initials: R
authors.lastname: Tal-Singer
authors.forename: David A
authors.initials: DA
authors.lastname: Lomas
authors.forename: Harvey O
authors.initials: HO
authors.lastname: Coxson
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Edwards
authors.forename: William
authors.initials: W
authors.lastname: MacNee
authors.forename: Jørgen
authors.initials: J
authors.lastname: Vestbo
authors.forename: Julie C
authors.initials: JC
authors.lastname: Yates
authors.forename: Alvar
authors.initials: A
authors.lastname: Agusti
authors.forename: Peter M A
authors.initials: PM
authors.lastname: Calverley
authors.forename: Bartolome
authors.initials: B
authors.lastname: Celli
authors.forename: Courtney
authors.initials: C
authors.lastname: Crim
authors.forename: Stephen
authors.initials: S
authors.lastname: Rennard
authors.forename: Emiel
authors.initials: E
authors.lastname: Wouters
authors.forename: Per
authors.initials: P
authors.lastname: Bakke
authors.forename: Amund
authors.initials: A
authors.lastname: Gulsvik
authors.forename: James D
authors.initials: JD
authors.lastname: Crapo
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
mesh_terms: D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*
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