Gene and environmental influences on childhood asthma: STELAR (Study Team for Early Life Asthma Research) collaboration

Asthma is the most common chronic disease of childhood and the number of children suffering from asthma has increased dramatically over the past 30 years. We do not fully understand what aspects of changing life style have caused this increase, but many things such as diet, immunizations and smoke exposure have been implicated. We have created a network of researchers from Aberdeen, Ashford, Bristol, Isle of White and Manchester and we have studied several thousand children from their birth and measured lots of factors in the environment (e.g. collecting dust form the home, recording dietary intake etc). Using questionnaires and lung function and allergy testing we have a clear description of which children have and have not got asthma and allergies. In each of the centres the study has used slightly different ways of measuring things. In this research project we will review the children in Manchester, Aberdeen and Ashford at age 10 -12 years and measure things in the same way. By working together as a research network we will be able to reproduce the findings of one cohort in another where similar measurements have been taken, making the research findings much stronger and more reliable. We are also collecting DNA from the study children and so in the future will be able to investigate how the genes and environment interact to cause disease. Understanding the causes of asthma will allow us to identify strategies to prevent asthma in susceptible children, and may improve treatment for asthma sufferers into adulthood.

Background: Asthma and allergies start early in life and are phenotypically unstable, progressing or remitting over time. The increase in their prevalence is consequent to environmental factors increasing the risk in genetically susceptible individuals (gene-environment interaction). Power to detect such interactions depends not only on size of population, but critically on accurate phenotyping and measurement of environmental exposures.
Aim: To study gene-environment interactions in the development of asthma and allergies
Methods: The STELAR group comprises all UK asthma/allergy birth cohorts (AMICS, SEATON, IoW, ALSPAC, MAAS). All cohorts are well established, all subjects are recruited and retention has been excellent. We propose to obtain a minimum set of common outcomes to provide comparable phenotypic definitions at similar time point (age 10-12 years) across the cohorts (?minimum dataset?) to allow pooling of data to increase power for genetic association studies. This includes:
Phenotyping: to collect outcome measures across 3 cohorts (AMICS, MAAS, SEATON) to give comparable phenotypes with that already collected in IoW and ALSPAC. Common phenotypic outcomes will comprise: physician-diagnosed asthma, current wheeze/wheeze phenotypes, lung function, airway reactivity, allergic sensitisation, Eczema/rhinitis.
Environmental exposures: to define a common set of environmental exposures (passive smoking, pet ownership, socioeconomic status, vaccination, childcare arrangements, position in sibship, allergen exposure, diet, household characteristics, antibiotic use, vitamin d, endotoxin)
Genotyping: to genotype for a common panel of SNPs to test for association with objective measures of lung function, sensitization and asthma. Our strategy will focus on specific gene-environment hypotheses including: TIM-1 and hepatitis A; Vitamins D and E, asthma and immune system; Environmental tobacco smoke exposure (ETS), polymorphisms in GST and changes in lung function; ADAM33 and ETS; Pattern recognition receptors, microbial exposures and allergy; ADRB2 and lung function; Leukotriene pathway and n-3 PUFA. In addition, we will investigate associations between putative candidate genes and asthma/allergy. This approach recognises that: each cohort is unique and has its strengths-there are unique hypotheses to test within each; where outcome measures are identical data can be merged to test the whole population; where outcome measures are similar (but not identical), findings can be replicated from one cohort in others.
Conclusions: This unique collaboration between all UK asthma/allergy birth cohorts will enable the establishment of a common genetic and environmental exposure database in children aged 10-12 years, exceeding the sum of the cohorts acting individually and putting UK in the forefront of the investigation of genetic and environmental influences on asthma.