A meta-analysis of potential genetic factors associated with antipsychotic-induced weight gain in adults with severe mental illness

Abstract

Introduction:

Genetic factors are thought to play an important role in antipsychotic-induced weight gain (AIWG). This study conducted a meta-analysis of current research of the pharmacogenetic associations of adult AIWG.

Methods:

The analysis included papers providing comparisons of weight gain across at least two allele combinations for at least one single nucleotide polymorphism (SNP). Inclusion criteria were, patients 18 years of age or older and had received a diagnosis of severe mental illness, for which antipsychotic medication was prescribed. The association with AIWG needed to be replicated across at least two papers reporting separate sample sets.

Results:

Two hundred twenty-three papers were assessed for eligibility. Of the 223 papers, 148 were excluded, leaving 75 studies to be included. Six SNPs in six different genes were identified as having significant associations (p < 0.05) with AIWG. These were HTR2C rs3813929 (TT + TC vs CC), Hedge’s g 0.76; MTHFR rs1801133 (TC + TT vs CC), Hedge’s g 0.61; ADRA2A rs1800544 (CC + CG vs GG), Hedge’s g 0.71; MC4R rs489693 (CC + AC vs AA) Hedge’s g 0.127; LEPR rs1137101 (GG + AG vs AA) Hedge’s g 0.18 and CNR1 rs104935 (GG + AG vs AA), Hedge’s g 0.55.

Conclusion:

The study identified six SNPs that predispose adult individuals to AIWG, with HTR2C rs3813929 and ADRA2A rs1800544 showing the largest effect sizes. Five of these have a role in hypothalamic regulation of appetite/satiety. Identification of these risk-associated SNPs may assist the development of a polygene/polyphenotypic risk score to identify individuals with psychosis who are at heightened risk of experiencing AIWG.