Family-based genetic risk prediction of multifactorial disease.docVIP

Ruderfer et al. Genome Medicine 2010, 2:2 /content/2/1/2 ME THOD Open Access Family-based genetic risk prediction of multifactorial disease 1,2,3 3 1,2,3,4 Douglas M Ruderfer , Joshua Korn and Shaun M Purcell* Abstract Genome-wide association studies have detected dozens of variants underlying complex diseases, although it is uncertain how often these discoveries will translate into clinically useful predictors. Here, to improve genetic risk prediction, we consider including phenotypic and genotypic information from related individuals. We develop and evaluate a family-based liability-threshold prediction model and apply it to a simulation of known Crohn’s disease risk variants. We show that genotypes of a relative of known phenotype can be informative for an individual’s disease risk, over and above the same locus genotyped in the individual. This approach can lead to better-calibrated estimates of disease risk, although the overall benet for prediction is typically only very modest. Background sought because a ?rst-degree relative has disease, we developed a family-based model for risk prediction incor- porating genotype data from both the index individual and Although whole-genome association studies have detected dozens of common variants for a broad range of complex diseases, and are likely to detect many more, the total a relative of known phenotype. As such, we do not ask variance explained by the known variants is typically ‘how well do single nucleotide polymorphisms predict modest [1,2]. As such, realising the goals of accurate disease compared to family history’, but rather, ‘how well genetic risk prediction and the subsequent opportunities do single nucleotide polymorphisms predict disease of personalised medicine remains di?cult [3,4]. Indeed, given a posi