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© Research
Publication : Proceedings of the National Academy of Sciences of the United States of America

Powerful gene-based testing by integrating long-range chromatin interactions and knockoff genotypes.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Proceedings of the National Academy of Sciences of the United States of America - 23 Nov 2021

Ma S, Dalgleish J, Lee J, Wang C, Liu L, Gill R, Buxbaum JD, Chung WK, Aschard H, Silverman EK, Cho MH, He Z, Ionita-Laza I,

Link to Pubmed [PMID] – 34799441

Link to DOI – e210519111810.1073/pnas.2105191118

Proc Natl Acad Sci U S A 2021 11; 118(47):

Gene-based tests are valuable techniques for identifying genetic factors in complex traits. Here, we propose a gene-based testing framework that incorporates data on long-range chromatin interactions, several recent technical advances for region-based tests, and leverages the knockoff framework for synthetic genotype generation for improved gene discovery. Through simulations and applications to genome-wide association studies (GWAS) and whole-genome sequencing data for multiple diseases and traits, we show that the proposed test increases the power over state-of-the-art gene-based tests in the literature, identifies genes that replicate in larger studies, and can provide a more narrow focus on the possible causal genes at a locus by reducing the confounding effect of linkage disequilibrium. Furthermore, our results show that incorporating genetic variation in distal regulatory elements tends to improve power over conventional tests. Results for UK Biobank and BioBank Japan traits are also available in a publicly accessible database that allows researchers to query gene-based results in an easy fashion.

https://pubmed.ncbi.nlm.nih.gov/34799441