Ethnic-specific associations of rare and low-frequency DNA sequence variants with asthma
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Author
Igartua, Catherine
Myers, Rachel A.
Mathias, Rasika A.
Pino-Yanes, Maria
Eng, Celeste
Graves, Penelope E.
Levin, Albert M.
Del-Rio-Navarro, Blanca E.
Jackson, Daniel J.
Livne, Oren E.
Rafaels, Nicholas
Edlund, Christopher K.
Yang, James J.
Huntsman, Scott
Salam, Muhammad T.
Romieu, Isabelle
Mourad, Raphael
Gern, James E.
Lemanske, Robert F.
Wyss, Annah
Hoppin, Jane A.
Barnes, Kathleen C.
Burchard, Esteban G.
Gauderman, W. James
Martinez, Fernando D.
Williams, L. Keoki
London, Stephanie J.
Gilliland, Frank D.
Nicolae, Dan L.
Ober, Carole
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/ncomms6965Metadata
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Igartua, C., R. A. Myers, R. A. Mathias, M. Pino-Yanes, C. Eng, P. E. Graves, A. M. Levin, et al. 2015. “Ethnic-specific associations of rare and low-frequency DNA sequence variants with asthma.” Nature Communications 6 (1): 5965. doi:10.1038/ncomms6965. http://dx.doi.org/10.1038/ncomms6965.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309441/pdf/Terms of Use
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http://nrs.harvard.edu/urn-3:HUL.InstRepos:14065343
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