Association between MTNR1B polymorphisms and obesity in African American: findings from the Jackson Heart Study
BACKGROUND: Melatonin is a hormone that is secreted at night by the pineal gland. It exerts its function by binding to the MT(1) and MT(2) receptors, which are encoded by the MTNR1A and MTNR1B genes, respectively. Previous studies reveal that MTNR1B variants are associated with insulin secretion imp...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138980/ https://www.ncbi.nlm.nih.gov/pubmed/34020621 http://dx.doi.org/10.1186/s12920-021-00983-2 |
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author | Tchio, Cynthia Musani, Solomon K. Quarshie, Alexander Tosini, Gianluca |
author_facet | Tchio, Cynthia Musani, Solomon K. Quarshie, Alexander Tosini, Gianluca |
author_sort | Tchio, Cynthia |
collection | PubMed |
description | BACKGROUND: Melatonin is a hormone that is secreted at night by the pineal gland. It exerts its function by binding to the MT(1) and MT(2) receptors, which are encoded by the MTNR1A and MTNR1B genes, respectively. Previous studies reveal that MTNR1B variants are associated with insulin secretion impairments and an increased body mass index (BMI) in individuals of European and Asian ancestries. Obesity is highly prevalent in the US and disproportionately affects African Americans. Here, we hypothesized 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. METHODS: We used an additive genetic model to describe the association between the adiposity traits (BMI and waist circumference) and selected MTNR1B variants in 3,029 Jackson Heart Study participants, with an average age of 55.13 ± 12.84 years, and 62% were women. We regressed the 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 a minor allele frequency ≥ 5%, a call rate ≥ 90%, a Hardy–Weinberg equilibrium p value > 10(–6), were available for the analysis. RESULTS: The allele T of rs76371840 was associated with adiposity (OR = 1.47 [1.13—1.82]; P(FDR-adjusted) = 0.0499), and the allele A of rs8192552 showed a significant association with waist circumference (β = 0.023 ± 0.007; P(FDR-adjusted) = 0.0077) after correcting for multiple testing. When insomnia was included in the adiposity analysis model, the following four variants became significantly associated with adiposity: rs6483208; rs4388843; rs4601728; and rs12804291. CONCLUSIONS: Our data indicate that polymorphisms in the MTNR1B gene are associated with obesity traits in African Americans. To the best of our knowledge, this is the first study to explore the effect of insomnia on the association between the circadian MTNR1B genetic variants and metabolic traits in an African American sample population. We observed that insomnia affected the association between the MTNR1B variants and adiposity. |
format | Online Article Text |
id | pubmed-8138980 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-81389802021-05-21 Association between MTNR1B polymorphisms and obesity in African American: findings from the Jackson Heart Study Tchio, Cynthia Musani, Solomon K. Quarshie, Alexander Tosini, Gianluca BMC Med Genomics Research Article BACKGROUND: Melatonin is a hormone that is secreted at night by the pineal gland. It exerts its function by binding to the MT(1) and MT(2) receptors, which are encoded by the MTNR1A and MTNR1B genes, respectively. Previous studies reveal that MTNR1B variants are associated with insulin secretion impairments and an increased body mass index (BMI) in individuals of European and Asian ancestries. Obesity is highly prevalent in the US and disproportionately affects African Americans. Here, we hypothesized 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. METHODS: We used an additive genetic model to describe the association between the adiposity traits (BMI and waist circumference) and selected MTNR1B variants in 3,029 Jackson Heart Study participants, with an average age of 55.13 ± 12.84 years, and 62% were women. We regressed the 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 a minor allele frequency ≥ 5%, a call rate ≥ 90%, a Hardy–Weinberg equilibrium p value > 10(–6), were available for the analysis. RESULTS: The allele T of rs76371840 was associated with adiposity (OR = 1.47 [1.13—1.82]; P(FDR-adjusted) = 0.0499), and the allele A of rs8192552 showed a significant association with waist circumference (β = 0.023 ± 0.007; P(FDR-adjusted) = 0.0077) after correcting for multiple testing. When insomnia was included in the adiposity analysis model, the following four variants became significantly associated with adiposity: rs6483208; rs4388843; rs4601728; and rs12804291. CONCLUSIONS: Our data indicate that polymorphisms in the MTNR1B gene are associated with obesity traits in African Americans. To the best of our knowledge, this is the first study to explore the effect of insomnia on the association between the circadian MTNR1B genetic variants and metabolic traits in an African American sample population. We observed that insomnia affected the association between the MTNR1B variants and adiposity. BioMed Central 2021-05-21 /pmc/articles/PMC8138980/ /pubmed/34020621 http://dx.doi.org/10.1186/s12920-021-00983-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Tchio, Cynthia Musani, Solomon K. Quarshie, Alexander Tosini, Gianluca Association between MTNR1B polymorphisms and obesity in African American: findings from the Jackson Heart Study |
title | Association between MTNR1B polymorphisms and obesity in African American: findings from the Jackson Heart Study |
title_full | Association between MTNR1B polymorphisms and obesity in African American: findings from the Jackson Heart Study |
title_fullStr | Association between MTNR1B polymorphisms and obesity in African American: findings from the Jackson Heart Study |
title_full_unstemmed | Association between MTNR1B polymorphisms and obesity in African American: findings from the Jackson Heart Study |
title_short | Association between MTNR1B polymorphisms and obesity in African American: findings from the Jackson Heart Study |
title_sort | association between mtnr1b polymorphisms and obesity in african american: findings from the jackson heart study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138980/ https://www.ncbi.nlm.nih.gov/pubmed/34020621 http://dx.doi.org/10.1186/s12920-021-00983-2 |
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