Ethnic-specific associations of rare and low-frequency DNA sequence variants with asthma.

Nat Commun 2015 Jan 16;6:5965. Epub 2015 Jan 16.

Department of Human Genetics, University of Chicago, 920 East 58th Street, CLSC 425, Chicago, Illinois 60637, USA.

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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http://dx.doi.org/10.1038/ncomms6965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309441PMC
January 2015
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References

(Supplied by CrossRef)
Article in Clin. Exp. Allergy
SF Thomsen et al.
Clin. Exp. Allergy 2010
Article in Am. Rev. Respir. Dis.
DL Duffy et al.
Am. Rev. Respir. Dis. 1990
Article in Eur. J. Hum. Genet.
LJ Palmer et al.
Eur. J. Hum. Genet. 2000
Article in Nat. Genet.
DG Torgerson et al.
Nat. Genet. 2011
Article in N. Engl. J. Med.
MF Moffatt et al.
N. Engl. J. Med. 2010
Article in Nat. Genet.
K Bønnelykke et al.
Nat. Genet. 2014
Article in Nat. Genet.
T Hirota et al.
Nat. Genet. 2011
Article in Nature
TA Manolio et al.
Nature 2009
Article in Trends Genet.
C Ober et al.
Trends Genet. 2011
Article in J. Allergy Clin. Immunol.
RA Myers et al.
J. Allergy Clin. Immunol. 2012
Article in Environ. Health Perspect.
MC Alavanja et al.
Environ. Health Perspect. 1996

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