INTRODUCTION: The tendency to develop asthma runs in families, but whether the severity of asthma symptoms is inherited is not known. OBJECTIVES: The aim of this study was to examine whether genetic factors influence the variation in the severity of asthma. METHODS: Of a sample of 21 133 adult twins from the Danish Twin Registry, a total of 575 subjects (256 intact pairs and 63 single twins) who themselves and/or their co-twins reported a history of asthma at a questionnaire survey were clinically examined. The severity of asthma symptoms was graded according to a clinical interview, and markers of airway impairment and allergy were measured. RESULTS: After adjusting for confounders, genetic factors explained 24% (10%-37%), P = 0.0004, of the variation in overall asthma symptom severity, whereas non-shared environment accounted for the remaining 76% of the variation. A significant genetic component was also found for the severity of specific asthma symptoms; wheezing 12% (3%-22%), P = 0.007 and shortness of breath 17% (7%-27%), P = 0.0006, but not for chest tightness and cough. Asthma symptom severity correlated weakly with rhinitis severity as well as with objective markers of lung function, airway inflammation, airway responsiveness and allergic sensitization. CONCLUSION: The individual variation in asthma symptom severity is to some degree influenced by genetic factors, but environmental factors explain the main part of the variation. The genetic architectures underlying the severity of asthma symptoms and objectively measured asthma-related traits, respectively, seem to differ.
INTRODUCTION: The tendency to develop asthma runs in families, but whether the severity of asthma symptoms is inherited is not known. OBJECTIVES: The aim of this study was to examine whether genetic factors influence the variation in the severity of asthma. METHODS: Of a sample of 21 133 adult twins from the Danish Twin Registry, a total of 575 subjects (256 intact pairs and 63 single twins) who themselves and/or their co-twins reported a history of asthma at a questionnaire survey were clinically examined. The severity of asthma symptoms was graded according to a clinical interview, and markers of airway impairment and allergy were measured. RESULTS: After adjusting for confounders, genetic factors explained 24% (10%-37%), P = 0.0004, of the variation in overall asthma symptom severity, whereas non-shared environment accounted for the remaining 76% of the variation. A significant genetic component was also found for the severity of specific asthma symptoms; wheezing 12% (3%-22%), P = 0.007 and shortness of breath 17% (7%-27%), P = 0.0006, but not for chest tightness and cough. Asthma symptom severity correlated weakly with rhinitis severity as well as with objective markers of lung function, airway inflammation, airway responsiveness and allergic sensitization. CONCLUSION: The individual variation in asthma symptom severity is to some degree influenced by genetic factors, but environmental factors explain the main part of the variation. The genetic architectures underlying the severity of asthma symptoms and objectively measured asthma-related traits, respectively, seem to differ.
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