BibTex format
@article{Sarnowski:2016:10.1016/j.jaci.2016.03.018,
author = {Sarnowski, C and Sugier, PE and Granell, R and Jarvis, D and Dizier, MH and Ege, M and Imboden, M and Laprise, C and Khusnutdinova, EK and Freidin, MB and Cookson, WO and Moffatt, M and Lathrop, M and Siroux, V and Ogorodova, LM and Karunas, AS and James, A and Probst-Hensch, NM and von, Mutius E and Pin, I and Kogevinas, M and Henderson, AJ and Demenais, F and Bouzigon, E},
doi = {10.1016/j.jaci.2016.03.018},
journal = {Journal of Allergy and Clinical Immunology},
pages = {1071--1080},
title = {Identification of a new locus at 16q12 associated with time to asthma onset},
url = {http://dx.doi.org/10.1016/j.jaci.2016.03.018},
volume = {138},
year = {2016}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - BackgroundAsthma is a heterogeneous disease in which age of onset plays an important role.ObjectiveWe sought to identify the genetic variants associated with time to asthma onset (TAO).MethodsWe conducted a large-scale meta-analysis of 9 genome-wide association studies of TAO (total of 5462 asthmatic patients with a broad range of age of asthma onset and 8424 control subjects of European ancestry) performed by using survival analysis techniques.ResultsWe detected 5 regions associated with TAO at the genome-wide significant level (P < 5 × 10−8). We evidenced a new locus in the 16q12 region (near cylindromatosis turban tumor syndrome gene [CYLD]) and confirmed 4 asthma risk regions: 2q12 (IL-1 receptor–like 1 [IL1RL1]), 6p21 (HLA-DQA1), 9p24 (IL33), and 17q12-q21 (zona pellucida binding protein 2 [ZPBP2]–gasdermin A [GSDMA]). Conditional analyses identified 2 distinct signals at 9p24 (both upstream of IL33) and 17q12-q21 (near ZPBP2 and within GSDMA). Together, these 7 distinct loci explained 6.0% of the variance in TAO. In addition, we showed that genetic variants at 9p24 and 17q12-q21 were strongly associated with an earlier onset of childhood asthma (P ≤ .002), whereas the 16q12 single nucleotide polymorphism was associated with later asthma onset (P = .04). A high burden of disease risk alleles at these loci was associated with earlier age of asthma onset (4 vs 9-12 years, P = 10−4).ConclusionThe new susceptibility region for TAO at 16q12 harbors variants that correlate with the expression of CYLD and nucleotide-binding oligomerization domain 2 (NOD2), 2 strong candidates for asthma. This study demonstrates that incorporating the variability of age of asthma onset in asthma modeling is a helpful approach in the search for disease susceptibility genes.
AU - Sarnowski,C
AU - Sugier,PE
AU - Granell,R
AU - Jarvis,D
AU - Dizier,MH
AU - Ege,M
AU - Imboden,M
AU - Laprise,C
AU - Khusnutdinova,EK
AU - Freidin,MB
AU - Cookson,WO
AU - Moffatt,M
AU - Lathrop,M
AU - Siroux,V
AU - Ogorodova,LM
AU - Karunas,AS
AU - James,A
AU - Probst-Hensch,NM
AU - von,Mutius E
AU - Pin,I
AU - Kogevinas,M
AU - Henderson,AJ
AU - Demenais,F
AU - Bouzigon,E
DO - 10.1016/j.jaci.2016.03.018
EP - 1080
PY - 2016///
SN - 1097-6825
SP - 1071
TI - Identification of a new locus at 16q12 associated with time to asthma onset
T2 - Journal of Allergy and Clinical Immunology
UR - http://dx.doi.org/10.1016/j.jaci.2016.03.018
VL - 138
ER -