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Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function.

Publication ,  Journal Article
Wyss, AB; Sofer, T; Lee, MK; Terzikhan, N; Nguyen, JN; Lahousse, L; Latourelle, JC; Smith, AV; Bartz, TM; Feitosa, MF; Gao, W; Ahluwalia, TS ...
Published in: Nat Commun
July 30, 2018

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

July 30, 2018

Volume

9

Issue

1

Start / End Page

2976

Location

England

Related Subject Headings

  • White People
  • Vital Capacity
  • Smoking
  • Sample Size
  • Regression Analysis
  • Quantitative Trait Loci
  • Pulmonary Disease, Chronic Obstructive
  • Polymorphism, Single Nucleotide
  • Male
  • Lung Diseases
 

Citation

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Wyss, A. B., Sofer, T., Lee, M. K., Terzikhan, N., Nguyen, J. N., Lahousse, L., … London, S. J. (2018). Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function. Nat Commun, 9(1), 2976. https://doi.org/10.1038/s41467-018-05369-0
Wyss, Annah B., Tamar Sofer, Mi Kyeong Lee, Natalie Terzikhan, Jennifer N. Nguyen, Lies Lahousse, Jeanne C. Latourelle, et al. “Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function.Nat Commun 9, no. 1 (July 30, 2018): 2976. https://doi.org/10.1038/s41467-018-05369-0.
Wyss AB, Sofer T, Lee MK, Terzikhan N, Nguyen JN, Lahousse L, et al. Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function. Nat Commun. 2018 Jul 30;9(1):2976.
Wyss, Annah B., et al. “Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function.Nat Commun, vol. 9, no. 1, July 2018, p. 2976. Pubmed, doi:10.1038/s41467-018-05369-0.
Wyss AB, Sofer T, Lee MK, Terzikhan N, Nguyen JN, Lahousse L, Latourelle JC, Smith AV, Bartz TM, Feitosa MF, Gao W, Ahluwalia TS, Tang W, Oldmeadow C, Duan Q, de Jong K, Wojczynski MK, Wang X-Q, Noordam R, Hartwig FP, Jackson VE, Wang T, Obeidat M, Hobbs BD, Huan T, Gui H, Parker MM, Hu D, Mogil LS, Kichaev G, Jin J, Graff M, Harris TB, Kalhan R, Heckbert SR, Paternoster L, Burkart KM, Liu Y, Holliday EG, Wilson JG, Vonk JM, Sanders JL, Barr RG, de Mutsert R, Menezes AMB, Adams HHH, van den Berge M, Joehanes R, Levin AM, Liberto J, Launer LJ, Morrison AC, Sitlani CM, Celedón JC, Kritchevsky SB, Scott RJ, Christensen K, Rotter JI, Bonten TN, Wehrmeister FC, Bossé Y, Xiao S, Oh S, Franceschini N, Brody JA, Kaplan RC, Lohman K, McEvoy M, Province MA, Rosendaal FR, Taylor KD, Nickle DC, Williams LK, Burchard EG, Wheeler HE, Sin DD, Gudnason V, North KE, Fornage M, Psaty BM, Myers RH, O’Connor G, Hansen T, Laurie CC, Cassano PA, Sung J, Kim WJ, Attia JR, Lange L, Boezen HM, Thyagarajan B, Rich SS, Mook-Kanamori DO, Horta BL, Uitterlinden AG, Im HK, Cho MH, Brusselle GG, Gharib SA, Dupuis J, Manichaikul A, London SJ. Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function. Nat Commun. 2018 Jul 30;9(1):2976.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

July 30, 2018

Volume

9

Issue

1

Start / End Page

2976

Location

England

Related Subject Headings

  • White People
  • Vital Capacity
  • Smoking
  • Sample Size
  • Regression Analysis
  • Quantitative Trait Loci
  • Pulmonary Disease, Chronic Obstructive
  • Polymorphism, Single Nucleotide
  • Male
  • Lung Diseases