The multi-ethnic study of atherosclerosis lung/snp health association resource study

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

doi:10.1164/rccm.201306-1061OC

The multi-ethnic study of atherosclerosis lung/snp health association resource study

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

Research output: Contribution to journal › Article › peer-review

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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 than2950 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 singlenucleotide 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 a-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 × 10210; MAF, 2.7%) and MGAT5B (rs7221059; P = 2.7 × 10^-8; MAF, 2.6%), which acts on a-linked mannose. Among African Americans, a locus near a third a-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 a-mannosidase may influence risk of emphysema.

Original language	English
Pages (from-to)	408-418
Number of pages	11
Journal	American Journal of Respiratory and Critical Care Medicine
Volume	189
Issue number	4
DOIs	https://doi.org/10.1164/rccm.201306-1061OC
State	Published - 15 Feb 2014

Keywords

Cohort study
Computed tomography
Emphysema
Genetic association
Multiethnic

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10.1164/rccm.201306-1061OC

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Manichaiku, A., Hoffman, E. A., Smolonska, J., Gao, W., Cho, M. H., Baumhauer, H., Budoff, M., Austin, J. H. M., Washko, G. R., Carr, J. J., Kaufman, J. D., Pottinger, T., Powell, C. A., Wijmenga, C., Zanen, P., Groen, H. J. M., Postma, D. S., Wanner, A., Rouhani, F. N., ... Barr, R. G. (2014). The multi-ethnic study of atherosclerosis lung/snp health association resource study. American Journal of Respiratory and Critical Care Medicine, 189(4), 408-418. https://doi.org/10.1164/rccm.201306-1061OC

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title = "The multi-ethnic study of atherosclerosis lung/snp health association resource study",

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 than2950 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 singlenucleotide 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 a-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 × 10210; MAF, 2.7%) and MGAT5B (rs7221059; P = 2.7 × 10-8; MAF, 2.6%), which acts on a-linked mannose. Among African Americans, a locus near a third a-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 a-mannosidase may influence risk of emphysema.",

keywords = "Cohort study, Computed tomography, Emphysema, Genetic association, Multiethnic",

author = "Ani Manichaiku and Hoffman, {Eric A.} and Joanna Smolonska and Wei Gao and Cho, {Michael H.} and Heather Baumhauer and Matthew Budoff and Austin, {John H.M.} and Washko, {George R.} and Carr, {J. Jeffrey} and Kaufman, {Joel D.} and Tess Pottinger and Powell, {Charles A.} and Cisca Wijmenga and Pieter Zanen and Groen, {Harry J.M.} and Postma, {Dirkje S.} and Adam Wanner and Rouhani, {Farshid N.} and Brantly, {Mark L.} and Rhea Powell and Smith, {Benjamin M.} and Dan Rabinowitz 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 Jos{\'e}e Dupuis and O'Connor, {George T.} and Boezen, {H. Marike} and Rich, {Stephen S.} and Barr, {R. Graham}",

year = "2014",

month = feb,

day = "15",

doi = "10.1164/rccm.201306-1061OC",

language = "English",

volume = "189",

pages = "408--418",

journal = "American Journal of Respiratory and Critical Care Medicine",

issn = "1073-449X",

publisher = "American Thoracic Society",

number = "4",

}

Manichaiku, A, Hoffman, EA, Smolonska, J, Gao, W, Cho, MH, Baumhauer, H, Budoff, M, Austin, JHM, Washko, GR, Carr, JJ, Kaufman, JD, Pottinger, T, Powell, CA, Wijmenga, C, Zanen, P, Groen, HJM, Postma, DS, Wanner, A, Rouhani, FN, Brantly, ML, Powell, R, Smith, BM, Rabinowitz, D, Raffel, LJ, Hinckley Stukovsky, KD, Crapo, JD, Beaty, TH, Hokanson, JE, Silverman, EK, Dupuis, J, O'Connor, GT, Boezen, HM, Rich, SS & Barr, RG 2014, 'The multi-ethnic study of atherosclerosis lung/snp health association resource study', American Journal of Respiratory and Critical Care Medicine, vol. 189, no. 4, pp. 408-418. https://doi.org/10.1164/rccm.201306-1061OC

TY - JOUR

T1 - The multi-ethnic study of atherosclerosis lung/snp health association resource study

AU - Manichaiku, Ani

AU - Hoffman, Eric A.

AU - Smolonska, Joanna

AU - Gao, Wei

AU - Cho, Michael H.

AU - Baumhauer, Heather

AU - Budoff, Matthew

AU - Austin, John H.M.

AU - Washko, George R.

AU - Carr, J. Jeffrey

AU - Kaufman, Joel D.

AU - Pottinger, Tess

AU - Powell, Charles A.

AU - Wijmenga, Cisca

AU - Zanen, Pieter

AU - Groen, Harry J.M.

AU - Postma, Dirkje S.

AU - Wanner, Adam

AU - Rouhani, Farshid N.

AU - Brantly, Mark L.

AU - Powell, Rhea

AU - Smith, Benjamin M.

AU - Rabinowitz, Dan

AU - Raffel, Leslie J.

AU - Hinckley Stukovsky, Karen D.

AU - Crapo, James D.

AU - Beaty, Terri H.

AU - Hokanson, John E.

AU - Silverman, Edwin K.

AU - Dupuis, Josée

AU - O'Connor, George T.

AU - Boezen, H. Marike

AU - Rich, Stephen S.

AU - Barr, R. Graham

PY - 2014/2/15

Y1 - 2014/2/15

N2 - 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 than2950 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 singlenucleotide 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 a-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 × 10210; MAF, 2.7%) and MGAT5B (rs7221059; P = 2.7 × 10-8; MAF, 2.6%), which acts on a-linked mannose. Among African Americans, a locus near a third a-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 a-mannosidase may influence risk of emphysema.

AB - 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 than2950 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 singlenucleotide 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 a-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 × 10210; MAF, 2.7%) and MGAT5B (rs7221059; P = 2.7 × 10-8; MAF, 2.6%), which acts on a-linked mannose. Among African Americans, a locus near a third a-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 a-mannosidase may influence risk of emphysema.

KW - Cohort study

KW - Computed tomography

KW - Emphysema

KW - Genetic association

KW - Multiethnic

UR - http://www.scopus.com/inward/record.url?scp=84894259001&partnerID=8YFLogxK

U2 - 10.1164/rccm.201306-1061OC

DO - 10.1164/rccm.201306-1061OC

M3 - Article

C2 - 24383474

AN - SCOPUS:84894259001

SN - 1073-449X

VL - 189

SP - 408

EP - 418

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

IS - 4

ER -

The multi-ethnic study of atherosclerosis lung/snp health association resource study

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