Estimating disease risk using genetic data

Project Summary
In the past years over genetic variants have been linked to complex human traits through
genome wide association studies GWAS However the predictive power of many of these variants
remains limited and it is still unclear how best to use the wealth of information generated by GWAS to
impact personal health and clinical practice For nearly years andMe has been not only a driving
force in direct to consumer genetic testing but also has established an innovative crowd sourced genetics
research platform This platform has yielded a compelling data resource and many genetic discoveries In
this proposal we will address the next phase of andMe human genetics research the development of
highly scalable and accurate disease risk estimation
Two of the key challenges in human genetics research are to determine how to use results of GWAS to
paint an accurate picture of an individualandapos s disease risk and to determine how these estimates can
provide information of personal and clinical utility These challenges are difficult due to many factors
including the wide spectrum of disease classes the paucity of genetic and phenotypic data and significant
methodological and computational challenges In this proposal we present a plan to utilize the genetic and
phenotypic data stores at andMe to develop validated risk estimation algorithms In Phase I we will
build a computational pipeline that will be used to develop predictive algorithms for estimating disease risk
Aim and use this pipeline to evaluate predictive ability of different estimation approaches in a broad
class of human complex traits Aim In Phase II we will validate these algorithms in external cohorts
and build customer facing reports that we will test for user comprehension
We believe that the development of accurate risk estimation capability will have a major impact on both
consumer genetics and clinical genetics markets

Project Narrative

The promise of genetics based estimation of disease risk has yet to be realized In this project andMe
will use its database of genetic and phenotypic information from over research participants who
have contributed more than phenotypic data points on a wide spectrum of disease to build
risk estimation algorithms This project will enable andMe to produce the first validated risk estimation
algorithms that provide both personal and clinical utility