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Circadian CLOCK gene polymorphisms in relation to sleep patterns and obesity in African Americans: findings from the Jackson heart study.

ABSTRACT: Circadian rhythms regulate key biological processes and the dysregulation of the intrinsic clock mechanism affects sleep patterns and obesity onset. The CLOCK (circadian locomotor output cycles protein kaput) gene encodes a core transcription factor of the molecular circadian clock influencing diverse metabolic pathways, including glucose and lipid homeostasis. The primary objective of this study was to evaluate the associations between CLOCK single nucleotide polymorphisms (SNPs) and body mass index (BMI). We also evaluated the association of SNPs with BMI related factors such as sleep duration and quality, adiponectin and leptin, in 2962 participants (1116 men and 1810 women) from the Jackson Heart Study. Genotype data for the selected 23 CLOCK gene SNPS was obtained by imputation with IMPUTE2 software and reference phase data from the 1000 genome project. Genetic analyses were conducted with PLINK RESULTS: We found a significant association between the CLOCK SNP rs2070062 and sleep duration, participants carriers of the T allele showed significantly shorter sleep duration compared to non-carriers after the adjustment for individual proportions of European ancestry (PEA), socio economic status (SES), body mass index (BMI), alcohol consumption and smoking status that reach the significance threshold after multiple testing correction. In addition, we found nominal associations of the CLOCK SNP rs6853192 with longer sleep duration and the rs6820823, rs3792603 and rs11726609 with BMI. However, these associations did not reach the significance threshold after correction for multiple testing.In this work, CLOCK gene variants were associated with sleep duration and BMI suggesting that the effects of these polymorphisms on circadian rhythmicity may affect sleep duration and body weight regulation in Africans Americans.

SUBMITTER: Riestra P

PROVIDER: S-EPMC5481932 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Circadian CLOCK gene polymorphisms in relation to sleep patterns and obesity in African Americans: findings from the Jackson heart study.

Riestra Pia P Gebreab Samson Y SY Xu Ruihua R Khan Rumana J RJ Gaye Amadou A Correa Adolfo A Min Nancy N Sims Mario M Davis Sharon K SK

BMC genetics 20170623 1

<h4>Background</h4>Circadian rhythms regulate key biological processes and the dysregulation of the intrinsic clock mechanism affects sleep patterns and obesity onset. The CLOCK (circadian locomotor output cycles protein kaput) gene encodes a core transcription factor of the molecular circadian clock influencing diverse metabolic pathways, including glucose and lipid homeostasis. The primary objective of this study was to evaluate the associations between CLOCK single nucleotide polymorphisms (S ...[more]

PMID: 28645331

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Project description:BackgroundMelatonin is a hormone that is secreted at night by the pineal gland. It exerts its function by binding to the MT1 and MT2 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.MethodsWe 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.ResultsThe allele T of rs76371840 was associated with adiposity (OR = 1.47 [1.13-1.82]; PFDR-adjusted = 0.0499), and the allele A of rs8192552 showed a 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 adiposity analysis model, the following four variants became significantly associated with adiposity: rs6483208; rs4388843; rs4601728; and rs12804291.ConclusionsOur 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.

Project description:Study objectivesStudies have shown that psychosocial stressors are related to poor sleep. However, studies of African Americans, who may be more vulnerable to the impact of psychosocial stressors, are lacking. Using the Jackson Heart Study (JHS) baseline data, we examined associations of psychosocial stressors with sleep in 4,863 African Americans.MethodsWe examined cross-sectional associations between psychosocial stressors and sleep duration and quality in a large population sample of African Americans. Three measures of psychosocial stress were investigated: the Global Perceived Stress Scale (GPSS); Major Life Events (MLE); and the Weekly Stress Inventory (WSI). Sleep was assessed using self-reported hours of sleep and sleep quality rating (1 = poor; 5 = excellent). Multinomial logistic and linear regression models were used to examine the association of each stress measure (in quartiles) with continuous and categorical sleep duration (< 5 ("very short"), 5-6 h ("short") and > 9 h ("long") versus 7 or 8 h ("normal"); and with sleep quality after adjustment for demographics and risk factors (body mass index, hypertension, diabetes, physical activity).ResultsMean age of the sample was 54.6 years and 64% were female. Mean sleep duration was 6.4 + 1.5 hours, 54% had a short sleep duration, 5% had a long sleep duration, and 34% reported a "poor" or "fair" sleep quality. Persons in the highest GPSS quartile had higher odds of very short sleep (odds ratio: 2.87, 95% confidence interval [CI]: 2.02, 4.08), higher odds of short sleep (1.72, 95% CI: 1.40, 2.12), shorter average sleep duration (Δ = -33.6 min (95% CI: -41.8, -25.4), and reported poorer sleep quality (Δ = -0.73 (95% CI: -0.83, -0.63) compared to those in the lowest quartile of GPSS after adjustment for covariates. Similar patterns were observed for WSI and MLE. Psychosocial stressors were not associated with long sleep. For WSI, effects of stress on sleep duration were stronger for younger (< 60 y) and college-educated African-Americans.ConclusionsPsychosocial stressors are associated with higher odds of short sleep, lower average sleep duration, and lower sleep quality in African Americans. Psychosocial stressors may be a point of intervention among African Americans for the improvement of sleep and downstream health outcomes.

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Circadian CLOCK gene polymorphisms in relation to sleep patterns and obesity in African Americans: findings from the Jackson heart study.

Publications

Circadian CLOCK gene polymorphisms in relation to sleep patterns and obesity in African Americans: findings from the Jackson heart study.

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