Insight gained from genome-wide interaction and enrichment analysis on weight gain during citalopram treatment

Abstract

Weight gain is a possible side effect of the pharmacological antidepressant treatments. Defining antidepressant prescriptions based on personal genetic makeups would decrease the risk of weight gain and increase the quality of the current antidepressant pharmacological treatments. 643 depressed, citalopram treated individuals with available clinical and genome-wide genetic information were investigated to identify the molecular pathways associated with weight gain. 111 individuals experienced weight gain during citalopram treatment. The axon guidance (p.adjust=0.005) and the developmental biology pathway (p.adjust=0.01) were enriched in variations associated with weight gain. The developmental biology pathway includes molecular cascades involved in the regulation of beta-cell development, and the transcriptional regulation of white adipocyte differentiation. A number of variations were harbored by genes whose products are involved in the synthesis of collagen (COL4A3, COL5A1 and ITGA1), activity of the thyroid-hormones (NCOR1 and NCOR2), energy metabolism (ADIPOQ, PPARGC1A) and myogenic differentiation (CDON). A molecular pathway analysis conducted in a sample of depressed patients identified new candidate genes whose future investigation may provide insights in the molecular events that drive weight gain during antidepressant treatment.

Keywords: Citalopram; GWAS; Molecular pathway; Weight gain.