Association of bmi with clock genetic variants
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This presentation summarizes a study examining the associations between sleep duration, BMI, macronutrient intake, and genetic variants. The study used data from 14,906 participants across 9 cohort studies. It found significant associations between sleep duration and BMI, with associations between sleep duration and intake being age- and sex-specific. The study also found that CLOCK genetic variants could modify the associations between sleep duration and dietary intake. While providing large-scale evidence, the study was limited to individuals of European descent and relied on self-reported sleep duration. It concluded that personalized sleep recommendations may have public health implications.
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Association of bmi with clock genetic variants
- 1. Welcome to my presentation Name: Hasan Al Banna Exam Roll: 1513 Reg. No.: Ha- 2515
- 2. Paper Title: Habitual sleep duration is associated with BMI and macronutrient intake, and may be modified by CLOCK genetic variants Name of Journal: The American Journal of Clinical Nutrition
- 3. Publishing Date: First online published November 26, 2014, Present edition: Am J Clin Nutr January 2015 vol. 101 no. 1 page 135-143 Authors: Hassan S Dashti, Jack L Follis, Caren E Smith, Toshiko Tanaka, Brian E Cade, Daniel J Gottlieb, Adela Hruby, Paul F Jacques, Stefania Lamon-Fava, Kris Richardson, Richa Saxena, Frank AJL Scheer, Leena Kovanen, Traci M Bartz, Mia-Maria Perälä, Anna Jonsson, Alexis C Frazier-Wood, Ioanna Panagiota Kalafati, Vera Mikkilä, Timo Partonen, Rozenn N Lemaitre, Jari Lahti, Dena G Hernandez, Ulla Toft, W Craig Johnson, Stavroula Kanoni, Olli T Raitakari, Markus Perola, Bruce M Psaty, Luigi Ferrucci, Niels Grarup, Heather M Highland, Loukianos Rallidis, Mika Kähönen, Aki S Havulinna, David S Siscovick, Katri Räikkönen, Torben Jørgensen, Jerome I Rotter, Panos Deloukas, Jorma SA Viikari, Dariush Mozaffarian, Allan Linneberg, Ilkka Seppälä, Torben Hansen, Veikko Salomaa, Sina A Gharib, Johan G Eriksson, Stefania Bandinelli, Oluf Pedersen, Stephen S Rich, George Dedoussis, Terho Lehtimäki, José M Ordovás.
- 4. Importance of the study Public Health Concern Obesity Hypertension Cardiovascular disease Mortality Diabetes Short Sleep Duration
- 5. Importance of the study (Continued…) Increase total energy intake and risk of obesity…. Influence appetite related hormone Sleep Restriction
- 6. Importance of the study (Continued……..) But….. We didn’t know the answer that •Whether chronic metabolic abnormalities associated with short sleep duration •Whether CLOCK variants modify the association between habitual short sleep duration and relative macronutrient intake
- 7. What was the objective of the study? Two basic objective the study: • Examining associations between habitual sleep duration, body mass index (BMI), and macronutrient intake a •Assessing whether CLOCK variants modify these associations. b
- 8. Methods used in the study • For habitual dietary intake data collection: Food Frequency Questionnaires (FFQ) o interviewer-administered FFQ o self-administered FFQ o modified-Block FFQ • Assessment methods for BMI calculation: Calculated from measured ratio from weight (kg) / height (m)2
- 9. Methods used in the study (Continued……..) • For Sleep duration data collection: By self-reported responses to questions • For tSNP selection The web-based service of the Tagger option within Haploview Software • For testing heterogeneity across studies Cochran’s Q statistic and quantified by using the I2 statistic
- 10. Uniform analysis plan… Associations between sleep duration and BMI were estimated by using linear regression models Investigated of associations between CLOCK tSNPs and dietary intake were by using linear fixed-effect regression models or linear mixed-effects models Investigation of the sleep duration and tSNP effect modification on dietary intake
- 11. Sample Collection • 14,906 participants of European descent from 9 cohort studies of the CHARGE Consortium Nutrition Working Group •Participants provided written informed consent •The protocol was approved by local institutional review boards and oversight committees.
- 12. Result Analysis
- 13. Continued……..
- 14. Continued……..
- 15. Summary of Result Identified a significant association between sleep duration and BMI Associations between sleep duration and intake tended to be age- and sex-specific CLOCK variants could modify the associations between sleep duration and dietary intake. Geographic location could have influenced these associations, particularly between CLOCK and PUFA.
- 16. Prospects for future study Geographic Difference Relevant to Chronic Disease Potential Interaction Elsewhere Other dimension of sleep
- 17. Limitation of the Study Interactions that met pre-specified criteria Limited to individuals of European descent Self-reported habitual sleep duration The temporal relation or the causal pathway linking CLOCK, sleep, and diet.
- 18. Concluding remarks One of the largest observational study Public health implications personalized sleep recommendations
- 19. Thanks to all…… Wish You All The Best Hasan Al Banna Exam Roll: 1513 Reg. No.: Ha- 2515 Department of Biochemistry and Molecular Biology University of Dhaka
Editor's Notes
- Assalamu Alaikum. This is Hasan Al Banna, welcome you all to this presentation of a research article.
- 1. My Paper Title is Habitual sleep duration is associated with BMI and macronutrient intake, and may be modified by CLOCK genetic variants 2. I have taken the original article from The American Journal of Clinical Nutrition BMI is a measure of relative size based on the mass and height of an individual. CLOCK is a transcription factor that affects both the persistence and period of circadian rhythms. CLOCK genetic variant ie Circadian Locomotor Output Cycles Kaput is a common genetic variants in the human which shows associations with ghrelin and total energy intake. The circadian clock makes it possible for organisms to coordinate their biology and behavior with daily and seasonal changes in the day-night cycle.
- The article is now available in the 101th volume of mentioned journal and was included on the current edition on 23rd January 2015 There worked 54 scientists in completing the research, who were from various universities, research institutes and organizations. They worked in several groups and contributed to different parts of the research
- It was found that fewer than 21% of U.S. adults met NIH recommendation of 7–8 h sleep/night. The increasing prevalence of short sleep duration raises public health concerns related to both safety and health This is because Short sleep duration has been associated with greater risks of obesity, hypertension, diabetes, and cardiovascular disease. and all increase mortality.
- 1. Studies of experimental sleep restriction showed unfavorable impacts on the appetite-related hormones ghrelin and leptin, on hunger & total energy intake. Self reported habitual short sleep duration is associated with elevated ghrelin and decreased leptin concentrations in the general population. 2. Ghrelin is is a peptide produced by ghrelin cells in the gastrointestinal tract which functions as a neuropeptide in the central nervous system. Beyond regulating hunger, ghrelin also plays a significant role in regulating the distribution and rate of use of energy. 3. Thus Sleep restriction was associated with increased energy intake, increased total fat and SFA intakes and excess consumption of carbohydrate-rich snacks.
- We didn’t have any confirmed report whether chronic metabolic abnormalities associated with short sleep duration result from differences in relative intakes of macronutrients. on the other hand CLOCK governs the sleep-wake cycle, also influences diet through changes in appetite mediated by endocrine hormones such as leptin, ghrelin, and insulin On the basis of the influence of CLOCK on appetite and total energy intake, we further hypothesized that CLOCK variants modify the association between habitual short sleep duration and relative macronutrient intake. So, as the answer could help us to take some important Public Health related decision, the study is certainly important
- So Two basic objective of the study stands as: Examining associations between habitual sleep duration, body mass index (BMI), and macronutrient intake Assessing whether CLOCK variants modify these associations.
- Habitual dietary intake data were collected via validated foodfrequency questionnaires (Supplemental Table 2) (19–24). The type of food-frequency questionnaire used in each cohort differed slightly to capture the dietary habits of the population of interest. The current analysis focused on intake as percentages of total energy of protein, carbohydrate, and total fat. In addition, we examined PUFA, MUFA, and SFA intakes as percentages of total energy.
- Data on habitual weekday/workday nighttime sleep duration in hours were obtained from self-reported responses to questions such as “How many hours of sleep do you usually get at night?” or were calculated from self-reported weekday/workday bed and rise times They selected 9 tagging single nucleotide polymorphisms (tSNPs) that capture variations for CLOCK gene and flanking regulatory regions by using the web-based service of the Tagger option (aggressive tagging approach) within Haploview Software. A tag SNP is a representative single nucleotide polymorphism (SNP) in a region of the genome with high linkage disequilibrium that represents a group of SNPs called ahaplotype. Haploview is a commonly used bioinformatics software which is designed to analyze and visualize patterns of linkage disequilibrium (LD) in genetic data. The heterogeneity across studies was tested by using Cochran’s Q statistic and quantified by using the I2 statistic They conducted sensitivity analyses to assess the influence on the meta-analyzed estimate of any single cohort study by repeating analyses with the removal of one cohort study at a time in both association and interaction analyses.
- So they worked following a Uniform analysis plan. First, main associations between sleep duration and BMI were estimated by using linear regression models with adjustment for age, sex, and, when relevant, study site. Second, main associations between CLOCK tSNPs and dietary intake were investigated by using linear fixed-effect regression models or linear mixedeffects models for cohorts with family data in an additive genetic model adjusted for age, sex, BMI, and, when relevant, study site and family or population substructure. Third, the sleep duration and tSNP effect modification on dietary intake was investigated by including an interaction term in a model adjusted for the aforementioned covariates. In a fixed-effects model, we are assuming that the true correlation estimated in each study is the same.
- The cross-sectional meta-analyses included up to 14,906 participants of European descent from the following 9 cohort studies of the CHARGE Consortium Nutrition Working Group Participants provided written informed consent, and the protocol was approved by local institutional review boards and oversight committees. The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium was formed to facilitate genome-wide association study meta-analyses and replication opportunities. What is Cohort? A group of people having approximately the same characteristics.
- 1. Overall, Each additional hour of sleep was associated with 0.16 lower BMI. In sex-stratified analyses, the magnitude of this association was approximately twice as great in men as women 2. We observed a significant association between sleep duration and SFA intake in younger adults whereby, per each additional hour of sleep, SFA intake was 0.11 6 0.06% (P = 0.03) and 0.10 6 0.05% (P = 0.04) lower in younger men and women 4. In addition, in older women, each additional hour of sleep was associated with 0.31 ± 0.12% (P , 0.01), 0.18 ± 0.09% (P = 0.05), and 0.05 ± 0.02% (P = 0.02) differences in percentages of energy from carbohydrate, total fat, and PUFAs. There were no significant associations between sleep duration and relative macronutrient intake adjusted for age, sex, BMI, and study site in the overall sample.
- A nominally significant (i.e., P , 0.05) association with the percentage of energy from MUFAs was observed at rs10462028 and percentage of energy from protein at rs504836 2. Sensitivity analyses showed that the association for rs1047354 with protein was driven by one cohort (HBCS) 3. Although overall meta-analyzed estimates of SNP associations show little evidence of heterogeneity results of the meta-regression revealed that geographic location (P , 0.05) might be a source of heterogeneity for several of the associations between tSNPs and PUFAs
- The following 2 nominally significant interactions were observed: between sleep duration and rs12649507 for PUFA, which suggested higher PUFA intake with each additional hour of sleep in the presence of the minor G allele, and Interaction between sleep duration and rs6858749 for energy from protein were observed, which suggested lower protein intake with each additional hour of sleep in the presence of the minor T allele.
- In meta-analyses of 9 cohorts, they showed that sleep duration was associated with BMI in the overall sample and relative macronutrient intake in specific age and sex groups. Stratified exploratory analyses indicated that associations between sleep duration and intake tended to be age- and sex-specific; For example: longer sleep duration was associated with lower SFA intake in younger adults and higher total fat intake They observed that CLOCK variants could modify the associations between sleep duration and dietary intake; however, these results were only nominally significant, some of which appeared to be region specific Meta-regression results indicated that geographic location could have influenced these associations, particularly between CLOCK and PUFA.
- 1. They report no associations between CLOCK variants and macronutrient composition; however, their results suggest that differences in intakes across geographic regions should be accounted for in future studies of the genetic component of dietary intake. 2. With the investigation of habitual lifestyle, including sleep and diet, our findings are potentially relevant to chronic diseases. Here needs further studies. 3. Although their analysis examined associations and interactions of a single circadian gene on dietary intake because of well-established biological pathways linking CLOCK to dietary intake, it is likely there are potentially important interactions elsewhere in the genome. 4. Although our investigation focused on nighttime sleep duration, which is a commonly surveyed sleep variable in large observational studies, the assessment of other dimensions of sleep, such as sleep quality, in addition to napping, which may have important effects on dietary intake, should also be considered.
- 1. A potential mechanistic overlap between effects of CLOCK and sleep duration on dietary intake led them to investigate potential gene 3 sleep duration interactions. Their interaction analyses failed to identify interactions that met pre-specified criteria for statistical significance. 2. The implications of their current study were limited to individuals of European descent, and additional analysis in other ethnic groups is warranted to generalize these findings. 3. Our use of self-reported habitual sleep duration and dietary intake was susceptible to reporting bias, and objective measures of sleep duration may be required for future studies. 4. The current crosssectional meta-analyses of observational studies could not inform us about the temporal relation or the causal pathway linking CLOCK, sleep, and diet. Therefore, whether sleep duration directly influenced dietary intake or indirectly moderated macronutrient effects on BMI, potentially through changes in substrate utilization, cannot be inferred from this investigation, and other studies are necessary to establish these mechanistic links.
- 1. Their meta-analysis of data from 9 cohort studies had several strengths. This was the largest observational study to investigate sleep duration with both BMI and dietary composition and the largest meta-analysis to investigate associations of CLOCK, as well as its interactions with sleep duration, with dietary intake. 2. The declining trends in habitual sleep duration and rising trends in metabolic abnormalities, their findings may have public health implications by providing recommendations to individuals at risk for chronic diseases. 3.The identified interaction provides preliminary findings for personalized sleep recommendations for individuals at increased genetic risk for obesity aimed at attenuating this risk
- I am grateful to all for your patience. So, if there is any question please proceed. Thank you all for you cooperation…