@article {1433710,
	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},
	journal = {Am J Respir Crit Care Med},
	volume = {189},
	number = {4},
	year = {2014},
	month = {2014 Feb 15},
	pages = {408-18},
	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 {\texttimes} 10(-8)) and PPT2 (rs10947233; P = 3.2 {\texttimes} 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 {\texttimes} 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 {\texttimes} 10(-10); MAF, 2.7\%) and MGAT5B (rs7221059; P = 2.7 {\texttimes} 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 {\texttimes} 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.},
	keywords = {Aged, Aged, 80 and over, alpha-Mannosidase, Female, Follow-Up Studies, Genetic Markers, Genome-Wide Association Study, Genotyping Techniques, Humans, Male, Mannosidases, Middle Aged, N-Acetylglucosaminyltransferases, Nerve Tissue Proteins, Polymorphism, Single Nucleotide, Pulmonary Emphysema, RNA Helicases, snRNP Core Proteins, Thiolester Hydrolases, Tomography, X-Ray Computed, United States},
	issn = {1535-4970},
	doi = {10.1164/rccm.201306-1061OC},
	author = {Manichaikul, Ani and Hoffman, Eric A and Smolonska, Joanna and Gao, Wei and Cho, Michael H and Baumhauer, Heather and Budoff, Matthew and Austin, John H M and Washko, George R and Carr, J Jeffrey and Kaufman, Joel D and Pottinger, Tess and Powell, Charles A and Wijmenga, Cisca and Zanen, Pieter and Groen, Harry J M and Postma, Dirkje S and Wanner, Adam and Rouhani, Farshid N and Brantly, Mark L and Powell, Rhea and Smith, Benjamin M and Rabinowitz, Dan and Raffel, Leslie J and Hinckley Stukovsky, Karen D and Crapo, James D and Beaty, Terri H and Hokanson, John E and Silverman, Edwin K and Dupuis, Jos{\'e}e and O{\textquoteright}Connor, George T and Boezen, H Marike and Rich, Stephen S and Barr, R Graham}
}