IGESS: a statistical approach to integrating individual-level genotype data and summary statistics in genome-wide association studies

摘要

>Motivation: Results from genome-wide association studies (GWAS) suggest that a complex phenotype is often affected by many variants with small effects, known as ‘polygenicity’. Tens of thousands of samples are often required to ensure statistical power of identifying these variants with small effects. However, it is often the case that a research group can only get approval for the access to individual-level genotype data with a limited sample size (e.g. a few hundreds or thousands). Meanwhile, summary statistics generated using single-variant-based analysis are becoming publicly available. The sample sizes associated with the summary statistics datasets are usually quite large. How to make the most efficient use of existing abundant data resources largely remains an open question. >Results: In this study, we propose a statistical approach, IGESS, to increasing statistical power of identifying risk variants and improving accuracy of risk prediction by integrating individual level genotype data and summary statistics. An efficient algorithm based on variational inference is developed to handle the genome-wide analysis. Through comprehensive simulation studies, we demonstrated the advantages of IGESS over the methods which take either individual-level data or summary statistics data as input. We applied IGESS to perform integrative analysis of Crohns Disease from WTCCC and summary statistics from other studies. IGESS was able to significantly increase the statistical power of identifying risk variants and improve the risk prediction accuracy from 63.2% (±0.4%) to 69.4% (±0.1%) using about 240 000 variants. >Availability and implementation: The IGESS software is available at . >Contact: or >Supplementary information: are available at Bioinformatics online.