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

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Abstract
Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genomewide 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 metaanalyses. 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.
Keywords
GENOME-WIDE ASSOCIATION, AIR-FLOW OBSTRUCTION, LUNG-FUNCTION, SEGREGATION ANALYSIS, SMOKING-BEHAVIOR, SMOOTH-MUSCLE, LARGE-SCALE, FOLLOW-UP, DISEASE, VARIANTS

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Chicago
Wyss, Annah B, Tamar Sofer, Mi Kyeong Lee, Natalie Terzikhan, Jennifer N Nguyen, Lies Lahousse, Jeanne C Latourelle, et al. 2018. “Multiethnic Meta-analysis Identifies Ancestry-specific and Cross-ancestry Loci for Pulmonary Function.” Nature Communications 9.
APA
Wyss, A. B., Sofer, T., Lee, M. K., Terzikhan, N., Nguyen, J. N., Lahousse, L., Latourelle, J. C., et al. (2018). Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function. NATURE COMMUNICATIONS, 9.
Vancouver
1.
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. NATURE COMMUNICATIONS. 2018;9.
MLA
Wyss, Annah B, Tamar Sofer, Mi Kyeong Lee, et al. “Multiethnic Meta-analysis Identifies Ancestry-specific and Cross-ancestry Loci for Pulmonary Function.” NATURE COMMUNICATIONS 9 (2018): n. pag. Print.
@article{8572850,
  abstract     = {Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genomewide 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 metaanalyses. 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.},
  articleno    = {2976},
  author       = {Wyss, Annah B and Sofer, Tamar and Lee, Mi Kyeong and Terzikhan, Natalie and Nguyen, Jennifer N and Lahousse, Lies and Latourelle, Jeanne C and Smith, Albert Vernon and Bartz, Traci M and Feitosa, Mary F and Gao, Wei and Ahluwalia, Tarunveer S and Tang, Wenbo and Oldmeadow, Christopher and Duan, Qing and de Jong, Kim and Wojczynski, Mary K and Wang, Xin-Qun and Noordam, Raymond and Hartwig, Fernando Pires and Jackson, Victoria E and Wang, Tianyuan and Obeidat, Ma'en and Hobbs, Brian D and Huan, Tianxiao and Gui, Hongsheng and Parker, Margaret M and Hu, Donglei and Mogil, Lauren S and Kichaev, Gleb and Jin, Jianping and Graff, Mariaelisa and Harris, Tamara B and Kalhan, Ravi and Heckbert, Susan R and Paternoster, Lavinia and Burkart, Kristin M and Liu, Yongmei and Holliday, Elizabeth G and Wilson, James G and Vonk, Judith M and Sanders, Jason L and Barr, R Graham and de Mutsert, Renee and Baptista Menezes, Ana Maria and Adams, Hieab HH and van den Berge, Maarten and Joehanes, Roby and Levin, Albert M and Liberto, Jennifer and Launer, Lenore J and Morrison, Alanna C and Sitlani, Colleen M and Celedon, Juan C and Kritchevsky, Stephen B and Scott, Rodney J and Christensen, Kaare and Rotter, Jerome I and Bonten, Tobias N and Wehrmeister, Fernando Cesar and Bosse, Yohan and Xiao, Shujie and Oh, Sam and Franceschini, Nora and Brody, Jennifer A and Kaplan, Robert C and Lohman, Kurt and McEvoy, Mark and Province, Michael A and Rosendaal, Frits R and Taylor, Kent D and Nickle, David C and Williams, L Keoki and Burchard, Esteban G and Wheeler, Heather E and Sin, Don D and Gudnason, Vilmundur and North, Kari E and Fornage, Myriam and Psaty, Bruce M and Myers, Richard H and O'Connor, George and Hansen, Torben and Laurie, Cathy C and Cassano, Patricia A and Sung, Joohon and Kim, Woo Jin and Attia, John R and Lange, Leslie and Boezen, H Marike and Thyagarajan, Bharat and Rich, Stephen S and Mook-Kanamori, Dennis O and Horta, Bernardo Lessa and Uitterlinden, Andre G and Im, Hae Kyung and Cho, Michael H and Brusselle, Guy and Gharib, Sina A and Dupuis, Josee and Manichaikul, Ani and London, Stephanie J},
  issn         = {2041-1723},
  journal      = {NATURE COMMUNICATIONS},
  language     = {eng},
  pages        = {15},
  title        = {Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function},
  url          = {http://dx.doi.org/10.1038/s41467-018-05369-0},
  volume       = {9},
  year         = {2018},
}

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