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.
abstract: BACKGROUND
  Pulmonary emphysema overlaps partially with spirometrically defined chronic obstructive pulmonary disease and is heritable, with moderately high familial clustering.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: 1 Center for Public Health Genomics, and.
authors.forename: Ani
authors.initials: A
authors.lastname: Manichaikul
authors.forename: Eric A
authors.initials: EA
authors.lastname: Hoffman
authors.forename: Joanna
authors.initials: J
authors.lastname: Smolonska
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.forename: Michael H
authors.initials: MH
authors.lastname: Cho
authors.forename: Heather
authors.initials: H
authors.lastname: Baumhauer
authors.forename: Matthew
authors.initials: M
authors.lastname: Budoff
authors.forename: John H M
authors.initials: JH
authors.lastname: Austin
authors.forename: George R
authors.initials: GR
authors.lastname: Washko
authors.forename: J Jeffrey
authors.initials: JJ
authors.lastname: Carr
authors.forename: Joel D
authors.initials: JD
authors.lastname: Kaufman
authors.forename: Tess
authors.initials: T
authors.lastname: Pottinger
authors.forename: Charles A
authors.initials: CA
authors.lastname: Powell
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.forename: Pieter
authors.initials: P
authors.lastname: Zanen
authors.forename: Harry J M
authors.initials: HJ
authors.lastname: Groen
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.forename: Adam
authors.initials: A
authors.lastname: Wanner
authors.forename: Farshid N
authors.initials: FN
authors.lastname: Rouhani
authors.forename: Mark L
authors.initials: ML
authors.lastname: Brantly
authors.forename: Rhea
authors.initials: R
authors.lastname: Powell
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Smith
authors.forename: Dan
authors.initials: D
authors.lastname: Rabinowitz
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Raffel
authors.forename: Karen D
authors.initials: KD
authors.lastname: Hinckley Stukovsky
authors.forename: James D
authors.initials: JD
authors.lastname: Crapo
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
authors.forename: John E
authors.initials: JE
authors.lastname: Hokanson
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
authors.forename: Josée
authors.initials: J
authors.lastname: Dupuis
authors.forename: George T
authors.initials: GT
authors.lastname: O'Connor
authors.forename: H Marike
authors.initials: HM
authors.lastname: Boezen
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: R Graham
authors.initials: RG
authors.lastname: Barr
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008361:Mannosidases / Q000235:genetics; D008875:Middle Aged; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging / Q000208:ethnology / Q000235:genetics*; D020365:RNA Helicases / Q000235:genetics; D013869:Thiolester Hydrolases / Q000235:genetics; D014057:Tomography, X-Ray Computed; D014481:United States / Q000453:epidemiology; D043323:alpha-Mannosidase / Q000235:genetics; D055517:snRNP Core Proteins / Q000235:genetics
chemical_list: D005819:Genetic Markers; D009419:Nerve Tissue Proteins; C526414:SNRPF protein, human; D055517:snRNP Core Proteins; C479741:MGAT5B protein, human; D017351:N-Acetylglucosaminyltransferases; D013869:Thiolester Hydrolases; C095299:palmitoyl-protein thioesterase; D008361:Mannosidases; C046090:mannosyl-oligosaccharide 1,2-alpha-mannosidase; D043323:alpha-Mannosidase; D020365:RNA Helicases