Genetics of Allergic Disease in a Participatory Research Cohort

DESCRIPTION (provided by applicant): Genetics of Allergic Disease in a Participatory Research Cohort Asthma and allergic disease are extremely common conditions with substantial public health burdens, affecting as many as one in five Americans. Discovery of genetic variants affecting allergic disease risk would contribute to our understanding of disease mechanisms as well as guide work towards improved diagnostics and treatments. Genome wide association studies (GWAS) have become well established as powerful tools for elucidating the genetic basis of disease. Recent experience with GWAS of complex traits shows that effect sizes at individual loci tend to be small, hence, the field has moved towards large, collaborative studies that combine data from multiplecohorts. In this context, the 23andMe participant cohort, with more than 100,000 genotyped individuals who have consented to participate in research, is a unique resource for studying the genetics of common disease. We have collected survey data in the 23andMe cohort covering a variety of asthma and allergy related phenotypes. More than 25,000 participants report one or more allergies, more than 8000 report an asthma diagnosis, and more than 5000 report having eczema. Our objective is to use the 23andMecohort to investigate the genetic and environmental basis of asthma and allergic disease. In Phase I, we will fully characterize and validate our self- reported phenotypes in the 23andMe cohort, and relate them to clinical definitions used in other studies. We will perform association studies informed by that phenotypic analysis, and participate in large consortia to meta-analyze GWAS for asthma and eczema. In Phase II, we will extend these studies to include additional phenotypes, treatment response, gene-gene, and gene-environment interactions as well as to incorporate additional participants recruited from new customers of the 23andMe Personal Genome Service(R). We will incorporate results of these studies into our Personal Genome Service(R), by developing new reports and enhancing existing reports on allergy phenotypes for 23andMe customers. These reports will include personalized risk assessments for allergic disease. This work will also demonstrate the strengths and scientific validity of the 23andMe research platform and set the stage for commercial research partnerships in the allergic disease area. PUBLIC HEALTH RELEVANCE: Asthma and allergic disease are extremely common conditions with substantial public health burdens, affecting as many one in five Americans. The proposed research will investigate the genetic and environmental contributions to allergic disease in the 23andMe participant cohort. Discovery of genetic variants affecting allergic disease risk would contribute to our understanding of disease mechanisms as well as guide work towards improved diagnostics and treatments.