Ethnic-specific associations of rare and low-frequency DNA sequence variants with asthma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

Catherine Igartua, Rachel A. Myers, Rasika A. Mathias, Maria Pino-Yanes, Celeste Eng, Penelope E. Graves, Albert M. Levin, Blanca E. Del-Rio-Navarro, Daniel J. Jackson, Oren E. Livne, Nicholas Rafaels, Christopher K. Edlund, James J. Yang, Scott Huntsman, Muhammad T. Salam, Isabelle Romieu, Raphael Mourad, James E. Gern, Robert F. Lemanske, Annah Wyss, Jane A. Hoppin, Kathleen C. Barnes, Esteban G. Burchard, W. James Gauderman, Fernando D. Martinez, Benjamin A. Raby, Scott T. Weiss, L. Keoki Williams, Stephanie J. London, Frank D. Gilliland, Dan L. Nicolae, Carole Ober

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. More... »

PAGES

5965

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms6965

DOI

http://dx.doi.org/10.1038/ncomms6965

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1031583418

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25591454


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