BACKGROUND: Atopic traits often co-occur and this can potentially be caused by common aetiological relationships between traits, i.e. a common genetic or a common environmental background. OBJECTIVE: To estimate to what extent the same genetic and environmental factors influence wheeze, rhinitis, airway hyper-responsiveness (AHR), and positive skin prick test (posSPT) in a sample of adult twins. METHODS: Within a sampling frame of 21,162 twin subjects, 20-49 years of age, from the Danish Twin Registry, a total of 575 subjects (256 intact pairs and 63 single twins), who either themselves and/or their co-twins reported a history of asthma at a nationwide questionnaire survey, were clinically examined. Symptoms of wheeze and rhinitis were obtained by interview; airway responsiveness and skin test reactivity were measured using standard techniques. Correlations in liability between the different traits were estimated and latent factor models of genetic and environmental effects were fitted to the observed data using maximum likelihood methods. RESULTS: The various phenotypic correlations between wheeze, rhinitis, AHR and posSPT were all significant and ranged between 0.50 and 0.86. Traits that showed highest genetic correlations were wheeze-rhinitis (rho(A)=0.95), wheeze-AHR (rho(A)=0.85) and rhinitis-posSPT (rho(A)=0.92), whereas lower genetic correlations were observed for rhinitis-AHR (rho(A)=0.43) and AHR-posSPT (rho(A)=0.59). Traits with a high degree of environmental sharing were rhinitis-posSPT (rho(E)=0.92) and wheeze-posSPT (rho(E)=0.71), whereas a lower environmental correlation was seen for wheeze-rhinitis (rho(E)=0.25). The estimates were corrected for ascertainment and adjusted for age, sex, inhaled corticosteroids and smoking. CONCLUSIONS: Different atopic conditions share, to a large extent, a common genetic background. In particular, upper and lower respiratory symptoms seem to be different phenotypic expressions of a common set of genes. These results add new insight into the origins of clinical heterogeneity within atopy and should stimulate the search for pleiotropic genes of importance for these conditions.
BACKGROUND: Atopic traits often co-occur and this can potentially be caused by common aetiological relationships between traits, i.e. a common genetic or a common environmental background. OBJECTIVE: To estimate to what extent the same genetic and environmental factors influence wheeze, rhinitis, airway hyper-responsiveness (AHR), and positive skin prick test (posSPT) in a sample of adult twins. METHODS: Within a sampling frame of 21,162 twin subjects, 20-49 years of age, from the Danish Twin Registry, a total of 575 subjects (256 intact pairs and 63 single twins), who either themselves and/or their co-twins reported a history of asthma at a nationwide questionnaire survey, were clinically examined. Symptoms of wheeze and rhinitis were obtained by interview; airway responsiveness and skin test reactivity were measured using standard techniques. Correlations in liability between the different traits were estimated and latent factor models of genetic and environmental effects were fitted to the observed data using maximum likelihood methods. RESULTS: The various phenotypic correlations between wheeze, rhinitis, AHR and posSPT were all significant and ranged between 0.50 and 0.86. Traits that showed highest genetic correlations were wheeze-rhinitis (rho(A)=0.95), wheeze-AHR (rho(A)=0.85) and rhinitis-posSPT (rho(A)=0.92), whereas lower genetic correlations were observed for rhinitis-AHR (rho(A)=0.43) and AHR-posSPT (rho(A)=0.59). Traits with a high degree of environmental sharing were rhinitis-posSPT (rho(E)=0.92) and wheeze-posSPT (rho(E)=0.71), whereas a lower environmental correlation was seen for wheeze-rhinitis (rho(E)=0.25). The estimates were corrected for ascertainment and adjusted for age, sex, inhaled corticosteroids and smoking. CONCLUSIONS: Different atopic conditions share, to a large extent, a common genetic background. In particular, upper and lower respiratory symptoms seem to be different phenotypic expressions of a common set of genes. These results add new insight into the origins of clinical heterogeneity within atopy and should stimulate the search for pleiotropic genes of importance for these conditions.
Authors: Truls S Ingebrigtsen; Simon F Thomsen; Sophie van der Sluis; Martin Miller; Kaare Christensen; Torben Sigsgaard; Vibeke Backer Journal: Lung Date: 2011-06-10 Impact factor: 2.584
Authors: Robert C Kern; David B Conley; William Walsh; Rakesh Chandra; Atsushi Kato; Anju Tripathi-Peters; Leslie C Grammer; Robert P Schleimer Journal: Am J Rhinol Date: 2008-09-10
Authors: Manuel A R Ferreira; Melanie C Matheson; Clara S Tang; Raquel Granell; Wei Ang; Jennie Hui; Amy K Kiefer; David L Duffy; Svetlana Baltic; Patrick Danoy; Minh Bui; Loren Price; Peter D Sly; Nicholas Eriksson; Pamela A Madden; Michael J Abramson; Patrick G Holt; Andrew C Heath; Michael Hunter; Bill Musk; Colin F Robertson; Peter Le Souëf; Grant W Montgomery; A John Henderson; Joyce Y Tung; Shyamali C Dharmage; Matthew A Brown; Alan James; Philip J Thompson; Craig Pennell; Nicholas G Martin; David M Evans; David A Hinds; John L Hopper Journal: J Allergy Clin Immunol Date: 2013-12-31 Impact factor: 10.793
Authors: Shu E Soh; Samuel Shang Ming Lee; Sarah Wenli Hoon; Mae Yun Tan; Anne Goh; Bee Wah Lee; Lynette Pei-Chi Shek; Oon Hoe Teoh; Kenneth Kwek; Seang Mei Saw; Keith Godfrey; Yap Seng Chong; Peter Gluckman; Hugo Ps van Bever Journal: Asia Pac Allergy Date: 2012-04-23
Authors: Ben D Spycher; John Henderson; Raquel Granell; David M Evans; George Davey Smith; Nicholas J Timpson; Jonathan A C Sterne Journal: J Allergy Clin Immunol Date: 2012-08 Impact factor: 10.793
Authors: Klaus Bønnelykke; Melanie C Matheson; Tune H Pers; Raquel Granell; David P Strachan; Alexessander Couto Alves; Allan Linneberg; John A Curtin; Nicole M Warrington; Marie Standl; Marjan Kerkhof; Ingileif Jonsdottir; Blazenka K Bukvic; Marika Kaakinen; Patrick Sleimann; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Katharina Schramm; Svetlana Baltic; Eskil Kreiner-Møller; Angela Simpson; Beate St Pourcain; Lachlan Coin; Jennie Hui; Eugene H Walters; Carla M T Tiesler; David L Duffy; Graham Jones; Susan M Ring; Wendy L McArdle; Loren Price; Colin F Robertson; Juha Pekkanen; Clara S Tang; Elisabeth Thiering; Grant W Montgomery; Anna-Liisa Hartikainen; Shyamali C Dharmage; Lise L Husemoen; Christian Herder; John P Kemp; Paul Elliot; Alan James; Melanie Waldenberger; Michael J Abramson; Benjamin P Fairfax; Julian C Knight; Ramneek Gupta; Philip J Thompson; Patrick Holt; Peter Sly; Joel N Hirschhorn; Mario Blekic; Stephan Weidinger; Hakon Hakonarsson; Kari Stefansson; Joachim Heinrich; Dirkje S Postma; Adnan Custovic; Craig E Pennell; Marjo-Riitta Jarvelin; Gerard H Koppelman; Nicholas Timpson; Manuel A Ferreira; Hans Bisgaard; A John Henderson Journal: Nat Genet Date: 2013-06-30 Impact factor: 38.330