PMID- 24311777
OWN - NLM
STAT- MEDLINE
DCOM- 20141016
LR  - 20140203
IS  - 1399-3003 (Electronic)
IS  - 0903-1936 (Linking)
VI  - 43
IP  - 2
DP  - 2014 Feb
TI  - Genetic heterogeneity of asthma phenotypes identified by a clustering approach.
PG  - 439-52
LID - 10.1183/09031936.00032713 [doi]
AB  - The aim of the study was to identify genetic variants associated with refined 
      asthma phenotypes enabling multiple features of the disease to be taken into 
      account. Latent class analysis (LCA) was applied in 3001 adults ever having 
      asthma recruited in the frame of three epidemiological surveys (the European 
      Community Respiratory Health Survey (ECRHS), the Swiss Study on Air Pollution and 
      Lung Disease in Adults (SAPALDIA) and the Epidemiological Study on the Genetics 
      and Environment of Asthma (EGEA)). 14 personal and phenotypic characteristics, 
      gathered from questionnaires and clinical examination, were used. A genome-wide 
      association study was conducted for each LCA-derived asthma phenotype, compared 
      to subjects without asthma (n=3474). The LCA identified four adult asthma 
      phenotypes, mainly characterised by disease activity, age of asthma onset and 
      atopic status. Associations of genome-wide significance (p<1.25 x 10(-7)) were 
      observed between "active adult-onset nonallergic asthma" and rs9851461 flanking 
      CD200 (3q13.2) and between "inactive/mild nonallergic asthma" and rs2579931 
      flanking GRIK2 (6q16.3). Borderline significant results (2.5 x 10(-7) < p <8.2 x 
      10(-7)) were observed between three single nucleotide polymorphisms (SNPs) in the 
      ALCAM region (3q13.11) and "active adult-onset nonallergic asthma". These results 
      were consistent across studies. 15 SNPs identified in previous genome-wide 
      association studies of asthma have been replicated with at least one asthma 
      phenotype, most of them with the "active allergic asthma" phenotype. Our results 
      provide evidence that a better understanding of asthma phenotypic heterogeneity 
      helps to disentangle the genetic heterogeneity of asthma.
FAU - Siroux, Valerie
AU  - Siroux V
AD  - Inserm, U823, Grenoble.
FAU - Gonzalez, Juan R
AU  - Gonzalez JR
FAU - Bouzigon, Emmanuelle
AU  - Bouzigon E
FAU - Curjuric, Ivan
AU  - Curjuric I
FAU - Boudier, Anne
AU  - Boudier A
FAU - Imboden, Medea
AU  - Imboden M
FAU - Anto, Josep Maria
AU  - Anto JM
FAU - Gut, Ivo
AU  - Gut I
FAU - Jarvis, Deborah
AU  - Jarvis D
FAU - Lathrop, Mark
AU  - Lathrop M
FAU - Omenaas, Ernst Reidar
AU  - Omenaas ER
FAU - Pin, Isabelle
AU  - Pin I
FAU - Wjst, Mathias
AU  - Wjst M
FAU - Demenais, Florence
AU  - Demenais F
FAU - Probst-Hensch, Nicole
AU  - Probst-Hensch N
FAU - Kogevinas, Manolis
AU  - Kogevinas M
FAU - Kauffmann, Francine
AU  - Kauffmann F
LA  - eng
GR  - R01HL62633-01/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20131205
PL  - England
TA  - Eur Respir J
JT  - The European respiratory journal
JID - 8803460
SB  - IM
MH  - Adult
MH  - Asthma/*diagnosis/*genetics
MH  - Cluster Analysis
MH  - Cohort Studies
MH  - Female
MH  - Follow-Up Studies
MH  - France
MH  - *Genetic Heterogeneity
MH  - Genetic Variation
MH  - Genome-Wide Association Study
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Phenotype
MH  - Polymorphism, Single Nucleotide
MH  - Reproducibility of Results
MH  - Switzerland
EDAT- 2013/12/07 06:00
MHDA- 2014/10/17 06:00
CRDT- 2013/12/07 06:00
PHST- 2013/12/07 06:00 [entrez]
PHST- 2013/12/07 06:00 [pubmed]
PHST- 2014/10/17 06:00 [medline]
AID - 09031936.00032713 [pii]
AID - 10.1183/09031936.00032713 [doi]
PST - ppublish
SO  - Eur Respir J. 2014 Feb;43(2):439-52. doi: 10.1183/09031936.00032713. Epub 2013 
      Dec 5.