A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations




Julkaisun tekijät: Sakornsakolpat P, Prokopenko D, Lamontagne M, Reeve NF, Guyatt AL, Jackson VE, Shrine N, Qiao DD, Bartz TM, Kim DK, Lee MK, Latourelle JC, Li XN, Morrow JD, Obeidat M, Wyss AB, Bakke P, Barr RG, Beaty TH, Belinsky SA, Brusselle GG, Crapo JD, de Jong K, DeMeo DL, Fingerlin TE, Gharib SA, Gulsvik A, Hall IP, Hokanson JE, Kim WJ, Lomas DA, London SJ, Meyers DA, O'Connor GT, Rennard SI, Schwartz DA, Sliwinski P, Sparrow D, Strachan DP, Tal-Singer R, Tesfaigzi Y, Vestbo J, Vonk JM, Yim JJ, Zhou XB, Bosse Y, Manichaikul A, Lahousse L, Silverman EK, Boezen HM, Wain LV, Tobin MD, Hobbs BD, Cho; SpiroMeta Consortium & International COPD Genetics Consortium
Kustantaja: NATURE PUBLISHING GROUP
Julkaisuvuosi: 2019
Journal: Nature Genetics
Tietokannassa oleva lehden nimi: NATURE GENETICS
Lehden akronyymi: NAT GENET
Volyymi: 51
Julkaisunumero: 1
Sivujen määrä: 14
ISSN: 1061-4036

Tiivistelmä
Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 x 10(-8); 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.

Last updated on 2019-16-04 at 15:52