Title: Ethnic-specific associations of rare and low-frequency DNA sequence variants with asthma.
Authors: 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; Raby, Benjamin A; Weiss, Scott T; Williams, L Keoki; London, Stephanie J; Gilliland, Frank D; Nicolae, Dan L; Ober, Carole
Published In Nat Commun, (2015 Jan 16)
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.
PubMed ID: 25591454
MeSH Terms: Asthma/genetics*; Carrier Proteins/genetics; Female; Genetic Predisposition to Disease/genetics; Genome-Wide Association Study/methods*; Humans; Linkage Disequilibrium/genetics; Male; Membrane Proteins/genetics; Neoplasm Proteins/genetics