Imperial College London
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Professor William Cookson

Faculty of Medicine, National Heart & Lung Institute

Professor of Genomic Medicine
 
 
 
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Contact

 

+44 (0)20 7594 2943w.cookson

 
 
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Location

 

400Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Sugier:2018:10.1016/j.jaci.2017.06.050,
author = {Sugier, P-E and Brossard, M and Sarnowski, C and Vaysse, A and Morin, A and Pain, L and Margaritte-Jeannin, P and Dizier, M-H and Cookson, WOCM and Lathrop, M and Moffatt, MF and Laprise, C and Demenais, F and Bouzigon, E},
doi = {10.1016/j.jaci.2017.06.050},
journal = {JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY},
pages = {1659--1667.e11},
title = {A novel role for ciliary function in atopy: ADGRV1 and DNAH5 interactions},
url = {http://dx.doi.org/10.1016/j.jaci.2017.06.050},
volume = {141},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundAtopy, an endotype underlying allergic diseases, has a substantial genetic component.ObjectiveOur goal was to identify novel genes associated with atopy in asthma-ascertained families.MethodsWe implemented a 3-step analysis strategy in 3 data sets: the Epidemiological Study on the Genetics and Environment of Asthma (EGEA) data set (1660 subjects), the Saguenay-Lac-Saint-Jean study data set (1138 subjects), and the Medical Research Council (MRC) data set (446 subjects). This strategy included a single nucleotide polymorphism (SNP) genome-wide association study (GWAS), the selection of related gene pairs based on statistical filtering of GWAS results, and text-mining filtering using Gene Relationships Across Implicated Loci and SNP-SNP interaction analysis of selected gene pairs.ResultsWe identified the 5q14 locus, harboring the adhesion G protein–coupled receptor V1 (ADGRV1) gene, which showed genome-wide significant association with atopy (rs4916831, meta-analysis P value = 6.8 × 10−9). Statistical filtering of GWAS results followed by text-mining filtering revealed relationships between ADGRV1 and 3 genes showing suggestive association with atopy (P ≤ 10−4). SNP-SNP interaction analysis between ADGRV1 and these 3 genes showed significant interaction between ADGRV1 rs17554723 and 2 correlated SNPs (rs2134256 and rs1354187) within the dynein axonemal heavy chain 5 (DNAH5) gene (Pmeta-int = 3.6 × 10−5 and 6.1 × 10−5, which met the multiple-testing corrected threshold of 7.3 × 10−5). Further conditional analysis indicated that rs2134256 alone accounted for the interaction signal with rs17554723.ConclusionBecause both DNAH5 and ADGRV1 contribute to ciliary function, this study suggests that ciliary dysfunction might represent a novel mechanism underlying atopy. Combining GWAS and epistasis analysis driven by statistical and knowledge-based evidence represents a promising approach for identifying ne
AU  - Sugier,P-E
AU  - Brossard,M
AU  - Sarnowski,C
AU  - Vaysse,A
AU  - Morin,A
AU  - Pain,L
AU  - Margaritte-Jeannin,P
AU  - Dizier,M-H
AU  - Cookson,WOCM
AU  - Lathrop,M
AU  - Moffatt,MF
AU  - Laprise,C
AU  - Demenais,F
AU  - Bouzigon,E
DO  - 10.1016/j.jaci.2017.06.050
EP  - 1667
PY  - 2018///
SN  - 0091-6749
SP  - 1659
TI  - A novel role for ciliary function in atopy: ADGRV1 and DNAH5 interactions
T2  - JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
UR  - http://dx.doi.org/10.1016/j.jaci.2017.06.050
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000432148200013&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/61478
VL  - 141
ER  -
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