Influence of MCHR2 and MCHR2-AS1 Genetic Polymorphisms on Body Mass Index in Psychiatric Patients and In Population-Based Subjects with Present or Past Atypical Depression

Abstract

Obesity development during psychotropic treatments represents a major health issue in psychiatry. Melanin-concentrating hormone receptor 2 (MCHR2) is a central receptor involved in energy homeostasis. MCHR2 shares its promoter region with MCHR2-AS1, a long antisense non-coding RNA. The aim of this study was to determine whether tagging single nucleotide polymorphisms (tSNPs) of MCHR2 and MCHR2-AS1 are associated with the body mass index (BMI) in the psychiatric and in the general population. The influence of MCHR2 and MCHR2-AS1 tSNPs on BMI was firstly investigated in a discovery psychiatric sample (n1 = 474). Positive results were tested for replication in two other psychiatric samples (n2 = 164, n3 = 178) and in two population-based samples (CoLaus, n4 = 5409; GIANT, n5 = 113809). In the discovery sample, TT carriers of rs7754794C>T had 1.08 kg/m2 (p = 0.04) lower BMI as compared to C-allele carriers. This observation was replicated in an independent psychiatric sample (-2.18 kg/m2; p = 0.009). The association of rs7754794C>T and BMI seemed stronger in subjects younger than 45 years (median of age). In the population-based sample, a moderate association was observed (-0.17 kg/m2; p = 0.02) among younger individuals (<45y). Interestingly, this association was totally driven by patients meeting lifetime criteria for atypical depression, i.e. major depressive episodes characterized by symptoms such as an increased appetite. Indeed, patients with atypical depression carrying rs7754794-TT had 1.17 kg/m2 (p = 0.04) lower BMI values as compared to C-allele carriers, the effect being stronger in younger individuals (-2.50 kg/m2; p = 0.03; interaction between rs7754794 and age: p-value = 0.08). This study provides new insights on the possible influence of MCHR2 and/or MCHR2-AS1 on obesity in psychiatric patients and on the pathophysiology of atypical depression.

Influence of polygenic risk scores on lipid levels and dyslipidemia in a psychiatric population receiving weight gain-inducing psychotropic drugs

“…Thus, population-based estimates could either under-or over-represent the influence of some SNPs in the psychiatric population, which may flatten the explained variability. As a matter of fact, the psychiatric population displays a greater influence of some genetic variants on metabolic features than does the general population, possibly because of an intricate interaction between the psychiatric illness and metabolic regulation [16,44] as well as a higher prevalence of metabolic abnormalities in this specific population [45].…”

“…Some factors were associated with psychotropic druginduced metabolic complications, including female sex, low baseline BMI, young age or non-white ethnicities [13]. Additionally, many genetic susceptibilities as variations in pharmacodynamic receptors or in energy homeostasis regulating genes were associated with metabolic side effects [14][15][16][17][18]. For instance, previous studies demonstrated the influence of 5HT 2C serotonin and H 1 histamine receptors on weight gain induced by psychotropic drugs [19,20].…”

A genome‐wide association study for a proxy of intermuscular fat level in the Italian Large White breed identifies genomic regions affecting an important quality parameter for dry‐cured hams

“…; Delacrétaz et al . ); PR domain containing 1, with ZNF domain ( PRDM1 ), which is involved in embryonic development and in the differentiation programs of different types of skeletal muscle fibres (Vincent et al . ); and PRSET domain 13 ( PRDM13 ), which is involved in neurological functions and associated with progressive increases in body weight and adiposity (Satoh et al .…”

Association of variants in SH2B1 and RABEP1 with worsening of low-density lipoprotein and glucose parameters in patients treated with psychotropic drugs

“…In addition, numerous single nucleotide polymorphisms (SNPs) within genes involved in other pathways of metabolism regulation (e.g. enzymes, receptors or transcriptional coactivators involved in leptin-melanocortin pathways, genes involved in cholesterol and/or in glucose homeostasis) were also associated with weight gain in psychiatric patients taking psychotropic drugs (18)(19)(20)(21)(22).…”

“…A growing body of evidence suggests that obesity and psychiatric diseases share common etiological pathways, which may be illustrated by the observed synergistic influence of genes associated with obesity and with psychiatric illness on cardiometabolic parameters (23). In addition, recent pharmacogenetic studies have shown stronger influence on obesity phenotypes of some BMI-associated genes in the psychiatric population treated with weight gain inducing psychotropic drugs compared to the general population (19)(20)(21). Unfortunately, it is unknown to which extent the 97 variants associated with BMI in the general population are associated with other cardiometabolic phenotypes in the psychiatric population, despite that such populations are at very high risk for cardiometabolic disorders.…”