Title: Genome-wide study of percent emphysema on computed tomography in the general population. The Multi-Ethnic Study of Atherosclerosis Lung/SNP Health Association Resource Study.

Authors: Manichaikul, Ani; Hoffman, Eric A; Smolonska, Joanna; Gao, Wei; Cho, Michael H; Baumhauer, Heather; Budoff, Matthew; Austin, John H M; Washko, George R; Carr, J Jeffrey; Kaufman, Joel D; Pottinger, Tess; Powell, Charles A; Wijmenga, Cisca; Zanen, Pieter; Groen, Harry J M; Postma, Dirkje S; Wanner, Adam; Rouhani, Farshid N; Brantly, Mark L; Powell, Rhea; Smith, Benjamin M; Rabinowitz, Dan; Raffel, Leslie J; Hinckley Stukovsky, Karen D; Crapo, James D; Beaty, Terri H; Hokanson, John E; Silverman, Edwin K; Dupuis, Josée; O'Connor, George T; Boezen, H Marike; Rich, Stephen S; Barr, R Graham

Published In Am J Respir Crit Care Med, (2014 Feb 15)

Abstract: RATIONALE: Pulmonary emphysema overlaps partially with spirometrically defined chronic obstructive pulmonary disease and is heritable, with moderately high familial clustering. OBJECTIVES: To complete a genome-wide association study (GWAS) for the percentage of emphysema-like lung on computed tomography in the Multi-Ethnic Study of Atherosclerosis (MESA) Lung/SNP Health Association Resource (SHARe) Study, a large, population-based cohort in the United States. METHODS: We determined percent emphysema and upper-lower lobe ratio in emphysema defined by lung regions less than -950 HU on cardiac scans. Genetic analyses were reported combined across four race/ethnic groups: non-Hispanic white (n = 2,587), African American (n = 2,510), Hispanic (n = 2,113), and Chinese (n = 704) and stratified by race and ethnicity. MEASUREMENTS AND MAIN RESULTS: Among 7,914 participants, we identified regions at genome-wide significance for percent emphysema in or near SNRPF (rs7957346; P = 2.2 × 10(-8)) and PPT2 (rs10947233; P = 3.2 × 10(-8)), both of which replicated in an additional 6,023 individuals of European ancestry. Both single-nucleotide polymorphisms were previously implicated as genes influencing lung function, and analyses including lung function revealed independent associations for percent emphysema. Among Hispanics, we identified a genetic locus for upper-lower lobe ratio near the α-mannosidase-related gene MAN2B1 (rs10411619; P = 1.1 × 10(-9); minor allele frequency [MAF], 4.4%). Among Chinese, we identified single-nucleotide polymorphisms associated with upper-lower lobe ratio near DHX15 (rs7698250; P = 1.8 × 10(-10); MAF, 2.7%) and MGAT5B (rs7221059; P = 2.7 × 10(-8); MAF, 2.6%), which acts on α-linked mannose. Among African Americans, a locus near a third α-mannosidase-related gene, MAN1C1 (rs12130495; P = 9.9 × 10(-6); MAF, 13.3%) was associated with percent emphysema. CONCLUSIONS: Our results suggest that some genes previously identified as influencing lung function are independently associated with emphysema rather than lung function, and that genes related to α-mannosidase may influence risk of emphysema.

PubMed ID: 24383474

MeSH Terms: No MeSH terms associated with this publication