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Updated: Apr 18, 2026

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Ethnic-specific associations of rare and low-frequency DNA sequence variants with asthma
Catherine Igartua1, Rachel A Myers1, Rasika A Mathias2
1Department of Human Genetics, University of Chicago, 920 East 58th Street, CLSC 425, Chicago, Illinois 60637, USA.
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.
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