@article{7d8a4ec0566d4816897c6549f6cbe9d3,
title = "Ethnic-specific associations of rare and low-frequency DNA sequence variants with asthma",
abstract = "Common variants at many loci have been robustly associated with asthma but explain little of the overall genetic risk. Here we investigate the role of rare (<1%) and low-frequency (1-5%) variants using the Illumina HumanExome BeadChip array in 4,794 asthma cases, 4,707 non-asthmatic controls and 590 case-parent trios representing European Americans, African Americans/African Caribbeans and Latinos. Our study reveals one low-frequency missense mutation in the GRASP gene that is associated with asthma in the Latino sample (P=4.31 × 10'6 OR=1.25; MAF=1.21%) and two genes harbouring functional variants that are associated with asthma in a gene-based analysis: GSDMB at the 17q12-21 asthma locus in the Latino and combined samples (P=7.81 × 10'8 and 4.09 × 10'8, respectively) and MTHFR in the African ancestry sample (P=1.72 × 10'6). Our results suggest that associations with rare and low-frequency variants are ethnic specific and not likely to explain a significant proportion of the €missing heritability € of asthma.",
author = "Catherine Igartua and Myers, {Rachel A.} and Mathias, {Rasika A.} and Maria Pino-Yanes and Celeste Eng and Graves, {Penelope E.} and Levin, {Albert M.} and Del-Rio-Navarro, {Blanca E.} and Jackson, {Daniel J.} and Livne, {Oren E.} and Nicholas Rafaels and Edlund, {Christopher K.} and Yang, {James J.} and Scott Huntsman and Salam, {Muhammad T.} and Isabelle Romieu and Raphael Mourad and Gern, {James E.} and Lemanske, {Robert F.} and Annah Wyss and Hoppin, {Jane A.} and Barnes, {Kathleen C.} and Burchard, {Esteban G.} and Gauderman, {W. James} and Martinez, {Fernando D.} and Raby, {Benjamin A.} and Weiss, {Scott T.} and Williams, {L. Keoki} and London, {Stephanie J.} and Gilliland, {Frank D.} and Nicolae, {Dan L.} and Carole Ober",
note = "Funding Information: This work was supported by NIH grants RC2 HL10165, P30 ES007048, P01 ES009581, P0 1ES01162, R01 HL118267 and R01 AI079139, the Intramural Research Program of the NIH (NIEHS Z01 CP010119, Z01 ES049030 and ES102385), the American Asthma Foundation, the Hastings Foundation, the Fund for Henry Ford Hospital and through resources provided by the Computation Institute and the Biological Sciences Division of the University of Chicago and Argonne National Laboratory (S10 RR029030-01). Genotyping services were provided by the Northwest Genomics Center at the University of Washington, Department of Genome Sciences, under US Federal Government contract number HHSN268201100037C from the National Heart, Lung and Blood Institute, and the Molecular Genomics Core at the University of Southern California (P30ES007048 and P01ES009581) and the Center for Inherited Disease Research at Johns Hopkins University. M.P.-Y. was funded by a Postdoctoral Fellowship from Fundaci{\'o}n Ram{\'o}n Areces. C.I. was supported by National Institutes of Health Grant T32 GM007197 and by the Ruth L. Kirschstein National Research Service Award (PA-11-112). KCB was supported in part by the Mary Beryl Patch Turnbull Scholar Program. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved.",
year = "2015",
month = jan,
doi = "10.1038/ncomms6965",
language = "English (US)",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}