Association Between MTNR1B Polymorphisms and Obesity in African American: Findings From The Jackson Heart Study

Abstract Background: Melatonin is a hormone secreted at night by the pineal gland that exerts its function by binding to MT1 and MT2 receptors encoded respectively by the MTNR1A and MTNR1B gene. Melatonin receptors are integral 7-transmembrane receptors called G-protein coupled receptors. Previous studies found that MTNR1B variants were associated with impairments in insulin secretion and increased body mass index (BMI) in individuals of European and Asian ancestries. Obesity is highly prevalent in the US, and disproportionately affect African Americans. We hypothesized here that common single nucleotide polymorphisms (SNPs) imputed in 1000 Genomes in the MTNR1B gene are associated with adiposity in African American adult men and women, and that the association is modified by insomnia. Results: We used an additive genetic model to describe the association between adiposity traits (BMI and waist circumference) and selected MTNR1B variants in 3,029 Jackson Heart Study participants with the average age 55.13±12.84 and 62% women. We regressed adiposity measures on the estimated allelic or genotypic dosage at every selected SNP and adjusted for age, sex, population stratification, and insomnia. Thirty common SNPs spanning the MTNR1B gene with minor allele frequency ≥5%, call rate ≥ 90%, Hardy-Weinberg equilibrium p-value > 10-6 were available for analysis. Conclusions: We found that allele T of rs76371840 was associated with adiposity (OR=1.47 [1.13 - 1.82]; PFDR-adjusted =0.0499 ), and allele A of rs8192552 showed significant association with waist circumference (β = 0.023 ± 0.007; PFDR-adjusted ­ =0.0077) after correcting for multiple testing. When insomnia was included in the model for the analysis of adiposity, the following four variants became significantly associated with adiposity; rs6483208, rs4388843, rs4601728, and rs12804291. In conclusion, our data indicate that polymorphisms in the MTNR1B gene are associated with obesity traits in African Americans.