Common genetic variants associated with resting oxygenation in chronic obstructive pulmonary disease.
Hypoxemia is a major complication of chronic obstructive pulmonary disease (COPD) that correlates with disease prognosis. Identifying genetic variants associated with oxygenation may provide clues for deciphering the heterogeneity in prognosis among patients with COPD. However, previous genetic studies have been restricted to investigating COPD candidate genes for association with hypoxemia. To report results from the first genome-wide association study (GWAS) of resting oxygen saturation (as measured by pulse oximetry [Spo2]) in subjects with COPD, we performed a GWAS of Spo2 in two large, well characterized COPD populations: COPDGene, including both the non-Hispanic white (NHW) and African American (AA) groups, and Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). We identified several suggestive loci (P < 1 × 10(-5)) associated with Spo2 in COPDGene in the NHW (n = 2810) and ECLIPSE (n = 1758) groups, and two loci on chromosomes 14 and 15 in the AA group (n = 820) from COPDGene achieving a level of genome-wide significance (P < 5 × 10(-8)). The chromosome 14 single-nucleotide polymorphism, rs6576132, located in an intergenic region, was nominally replicated (P < 0.05) in the NHW group from COPDGene. The chromosome 15 single-nucleotide polymorphisms were rare in subjects of European ancestry, so the results could not be replicated. The chromosome 15 region contains several genes, including TICRR and KIF7, and is proximal to RHCG (Rh family C glyocoprotein gene). We have identified two loci associated with resting oxygen saturation in AA subjects with COPD, and several suggestive regions in subjects of European descent with COPD. Our study highlights the importance of investigating the genetics of complex traits in different racial groups.
1 Channing Division of Network Medicine, and.
Merry-Lynn N
ML
McDonald
Michael H
MH
Cho
Inga-Cecilie
IC
Sørheim
Sharon M
SM
Lutz
Peter J
PJ
Castaldi
David A
DA
Lomas
Harvey O
HO
Coxson
Lisa D
LD
Edwards
William
W
MacNee
Jørgen
J
Vestbo
Julie C
JC
Yates
Alvar
A
Agusti
Peter M A
PM
Calverley
Bartolome
B
Celli
Courtney
C
Crim
Stephen I
SI
Rennard
Emiel F M
EF
Wouters
Per
P
Bakke
Ruth
R
Tal-Singer
Bruce E
BE
Miller
Amund
A
Gulsvik
Richard
R
Casaburi
J Michael
JM
Wells
Elizabeth A
EA
Regan
Barry J
BJ
Make
John E
JE
Hokanson
Christoph
C
Lange
James D
JD
Crapo
Terri H
TH
Beaty
Edwin K
EK
Silverman
Craig P
CP
Hersh
D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010092:Oximetry; D010100:Oxygen / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism*; D012146:Rest / Q000502:physiology; D044465:White People / Q000235:genetics*
D010100:Oxygen
chronic obstructive pulmonary disease; genome-wide association study; hypoxemia; oxygen saturation; pulse oximetry