A powerful statistical method identifies novel loci associated with diastolic blood pressure triggered by nonlinear gene-environment interaction

Abstract

The genetic basis of blood pressure often involves multiple genetic factors and their interactions with environmental factors. Gene-environment interaction is assumed to play an important role in determining individual blood pressure variability. Older people are more prone to high blood pressure than younger ones and the risk may not display a linear trend over the life span. However, which gene shows sensitivity to aging in its effect on blood pressure is not clear. In this work, we allowed the genetic effect to vary over time and propose a varying-coefficient model to identify potential genetic players that show nonlinear response across different age stages. We detected 2 novel loci, gene MIR1263 (a microRNA coding gene) on chromosome 3 and gene UNC13B on chromosome 9, that are nonlinearly associated with diastolic blood pressure. Further experimental validation is needed to confirm this finding.