Etiological Relationships in Atopy: A Review of Twin Studies

Abstract

The genetics of asthma and atopy has been studied frequently in twin populations from various parts of the world. However, emphasis has been put on univariate analysis of questionnaire data, whereas clinical and intermediate traits only sporadically have been studied, especially in multivariate settings. This review focuses on multivariate twin studies of atopy and related traits. We conclude that the genetic liability to most atopic traits is significantly correlated but that trait-specific genes also play a role. Previous studies have estimated the genetic correlation between upper and lower respiratory allergic symptoms, that is, asthma and hay fever, to be between .47 and .95. Furthermore, atopic traits share a portion of their genetic determinants with other complex disorders like obesity and behavioral traits. A correlation of about .3 and .34 has been reported between genes associated with asthma and obesity, and between genes associated with asthma and depression, respectively. We emphasize that multivariate methods applied to twin studies, especially when genetic marker information is available, provide a valuable framework within which complex etiological mechanisms underlying atopy can be disentangled.

Respiratory Syncytial Virus and Asthma in Twin Children: Lessons from the Population-Based Danish Registries

“…Earlier twin studies among children from Scandinavia and other countries have found that the risk of asthma in MZ twins is increased approximately 5-fold relative to the background population, whereas the risk in DZ twins is increased approximately 2-fold [36]. These findings are consistent with a substantial genetic component for asthma with a heritability contribution of around 70%.…”

Genetic and environmental influences on objective intermediate asthma phenotypes in Dutch twins

“…Twin and family studies are widely used to estimate genetic and environmental contributions to atopic disease [5,6]. The multivariate classical twin design can help to estimate the degree to which the same genetic and environmental factors influence different intermediate phenotypes [7].…”

“…If there is overlap in genes for two traits it is expected that the cross-twin cross-trait correlation will be higher in monozygotic (MZ) twins than in dizygotic (DZ) twins for these traits. Using this information cannot only widen our understanding of atopic comorbidity, it can also enhance gene-mapping efforts [6] and consequently enable us to understand the interplay between different pathways underlying asthma, benefitting the discovery of targeted treatments and interventional measures.…”

Are Specific Allergen Sensitivities Inherited?

“…Twin studies have been a valuable source of data to examine the role of genetics in monozygotic (MZ) compared with dizygotic (DZ) twins and have provided support for the hypothesis that allergic disorders have a genetic predisposition [8,9]. Clarke et al [10] found an increased association within MZ twins compared to within DZ twins for asthma (MZ: OR, 25.6; 95% CI, 11.3-57.8 vs DZ: OR, 1.9; 95% CI, 1.0-3.5), allergen sensitization (MZ: OR, 14.6; 95% CI, 7.1-30.1 vs DZ: OR, 2.5; 95% CI, 1.4-4.5), and bronchial hyperreactivity (MZ: OR, 14.1; 95% CI, 6.4-31.0 vs DZ: OR, 4.2; 95% CI, 2.1-8.6).…”

“…The data regarding specific IgE inheritance are increasingly complex, with some twin studies suggesting that overall atopy is under stronger genetic control than sensitization to individual allergens [9]. Wuthrich et al [11] found that concordance rates were not significantly different between the skin prick test results of 30 MZ and 20 DZ twin pairs when they were tested for 7 different allergens (D. pteronyssinus, Timothy grass, birch, hazel, dogs, cats, and horses).…”