RT Journal Article
SR Electronic
T1 Surfactant protein D is a causal risk factor for COPD: results of Mendelian randomisation
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1700657
DO 10.1183/13993003.00657-2017
VO 50
IS 5
A1 Ma'en Obeidat
A1 Xuan Li
A1 Stephen Burgess
A1 Guohai Zhou
A1 Nick Fishbane
A1 Nadia N. Hansel
A1 Yohan Bossé
A1 Philippe Joubert
A1 Ke Hao
A1 David C. Nickle
A1 Maarten van den Berge
A1 Wim Timens
A1 Michael H. Cho
A1 Brian D. Hobbs
A1 Kim de Jong
A1 Marike Boezen
A1 Rayjean J. Hung
A1 Nicholas Rafaels
A1 Rasika Mathias
A1 Ingo Ruczinski
A1 Terri H. Beaty
A1 Kathleen C. Barnes
A1 Peter D. Paré
A1 Don D. Sin
A1 ,
YR 2017
UL http://erj.ersjournals.com/content/50/5/1700657.abstract
AB Surfactant protein D (SP-D) is produced primarily in the lung and is involved in regulating pulmonary surfactants, lipid homeostasis and innate immunity. Circulating SP-D levels in blood are associated with chronic obstructive pulmonary disease (COPD), although causality remains elusive.In 4061 subjects with COPD, we identified genetic variants associated with serum SP-D levels. We then determined whether these variants affected lung tissue gene expression in 1037 individuals. A Mendelian randomisation framework was then applied, whereby serum SP-D-associated variants were tested for association with COPD risk in 11 157 cases and 36 699 controls and with 11 years decline of lung function in the 4061 individuals.Three regions on chromosomes 6 (human leukocyte antigen region), 10 (SFTPD gene) and 16 (ATP2C2 gene) were associated with serum SP-D levels at genome-wide significance. In Mendelian randomisation analyses, variants associated with increased serum SP-D levels decreased the risk of COPD (estimate −0.19, p=6.46×10−03) and slowed the lung function decline (estimate=0.0038, p=7.68×10−3).Leveraging genetic variation effect on protein, lung gene expression and disease phenotypes provided novel insights into SP-D biology and established a causal link between increased SP-D levels and protection against COPD risk and progression. SP-D represents a very promising biomarker and therapeutic target for COPD.Surfactant protein D is a causal risk factor for COPD http://ow.ly/n1OG30eUQlf