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Objective: The underlying model of the genetic determinant of a trait is generally not known with certainty a priori. Hence, in genetic association studies, a dominant model might be erroneously modelled as additive, an error investigated previously. We explored this question, for candidate gene studies, by evaluating the sample size required to compensate for the misspecification and improve inference at the analysis stage. Power calculations were carried out with (1) the true dominant model and (2) the incorrect additive model. Empirical power, sample size and effect size were compared between scenarios (1) and (2). In each of the scenarios the estimates were evaluated for a rare (minor allele frequency < 0.01), low frequency (0.01 ≤ minor allele frequency < 0.05) and common (minor allele frequency ≥ 0.05) single nucleotide polymorphism. Results: The results confirm the detrimental effect of the misspecification error on power and effect size for any minor allele frequency. The implications of the error are not negligible; therefore, candidate gene studies should consider the more conservative sample size to compensate for the effect of error. When it is not possible to extend the sample size, methods that help mitigate the impact of the error should be systematically used. [ABSTRACT FROM AUTHOR]

Background: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: Recent emphasis has been placed on elucidating the biologic mechanism linking socioeconomic status (SES) to cardiovascular disease (CVD). Positive associations of inflammatory biomarkers provide evidence suggestive of a biologic pathway by which SES may predispose to CVD. African Americans have disproportionately lower SES and have a higher prevalence of CVD risk factors compared to most ethnic/racial groups. Adiponectin (an anti-inflammatory marker) is also lower. The objective of this study was to assess the association of adiponectin with SES among African American men and women using the Jackson Heart Study.Methods: Study sample included 4340 participants. Linear regression was performed separately by SES and stratified by sex. Annual household income and level of education was used as proxies for SES. Crude, age, health behavior and health status adjusted models were analyzed. The main outcome was log-transformed adiponectin.Results: Men in the lowest income group had significantly higher adiponectin than those in the highest income group in the fully adjusted model (ß/standard error [se], p value = .16/.08, p = .0008. Men with < high school level of education had significantly higher adiponectin in the crude and age adjusted models than those with ≥ college degree (.25/.05, p < .0001; .14/.05/ p = .005, respectively). Women with some college or vocational training in the crude and age adjusted models had lower adiponectin compared to women with ≥ college degree (-.09/.03, p = .004; -.06/.03, p = .04, respectively).Conclusion: Findings suggest a potential inverse biologic pathway between annual household income and adiponectin among African American men. There was no such finding among women. Findings suggest interventions should be targeted for higher SES African American men to improve adiponectin levels. [ABSTRACT FROM AUTHOR]

Background: African Americans experience disproportionately higher prevalence of type 2 diabetes and related risk factors. Little research has been done on the association of ADIPOQ gene on type 2 diabetes, plasma adiponectin, blood glucose, HOMA-IR and body mass index (BMI) in African Americans. The objective of our research was to assess such associations with selected SNPs. The study included a sample of 3,020 men and women from the Jackson Heart Study who had ADIPOQ genotyping information. Unadjusted and adjusted regression models with covariates were used with type 2 diabetes and related phenotypes as the outcome stratified by sex. Results: There was no association between selected ADIPOQ SNPs with type 2 diabetes, blood glucose, or BMI in men or women. There was a significant association between variant rs16861205 and lower adiponectin in women with minor allele A in the fully adjusted model (β(SE) p = -.13(0.05), 0.003). There was also a significant association with variant rs7627128 and lower HOMA-IR among men with minor allele A in the fully adjusted model (β(SE) p = -0.74(0.20), 0.0002). Conclusions: These findings represent new insights regarding the association of ADIPOQ gene and type 2 diabetes and related phenotypes in African American men and women. [ABSTRACT FROM AUTHOR]

Background: Despite the important role of adiponectin in regulating general metabolic homeostasis, analysis of genetic determinants of adiponectin and the related cardio-metabolic traits in African American population has been limited and inconsistent. Considering the high genetic admixture of African Americans and thus the important population stratification that may confound the genetic-trait associations, the objective of this work was to perform a comprehensive analysis of the associations between ADIPOQ variants and adiponectin levels and obesity phenotypes in a large African American population from the Jackson Heart Study (JHS) cohort. Methods: Genotype data was available for 2968 JHS participants (1131men; 1837women). Single Nucleotide Polymorphisms (SNPs) were selected by a Tag-SNP Approach and literature review. The genotype imputation was performed using IMPUTE2 software and reference phased data from the 1000G project. PLINK software was used for the genetic analysis. Plasma specimens were analyzed by ELISA for adiponectin levels. All analyses were controlled for population stratification assessed by Individual Proportions of European Ancestry (PEA) estimates calculated in HAPMIX using ancestry informative markers (AIMs). Results: We found a gender-dependent association of some ADIPOQ variants and adiponectin levels. In women four of the studied polymorphisms (rs6444174, rs16861205, rs1403697, rs7641507) were associated with adiponectin levels after Bonferroni correction and controlling for the percentage of PEA, age, annual household income and smoking. These results were consistent with the haplotype analysis. The association between the rs12495941 variant and obesity is modulated by the PEA, so that the relationship between the G allele and a higher incidence of obesity was present in those individuals within the lower PEA group. In addition we found an effect modification of obesity on the association between the ADIPOQ rs6444174 SNP and BMI so that the presence of the T allele was negatively and significantly associated with BMI only in participants with a normal weight. Conclusions: In this large African American cohort, ADIPOQ variants were associated with adiponectin levels in a gender-dependent manner and the relationship of some of these variants with obesity and BMI was modulated by the PEA and obesity status respectively. This suggests that the effects of these polymorphisms on adiponectin and obesity phenotypes are subject to a strong interaction with genetic and environmental factors in African American population. [ABSTRACT FROM AUTHOR]

Background: Adiponectin is a biomarker that is associated with type 2 diabetes and hypertension. Lower circulating level is a risk factor. Higher levels are protective. African Americans have a higher prevalence of type 2 diabetes and hypertension and lower levels of adiponectin when compared to other racial/ethnic groups. Little is known about the association of adiponectin on these health outcomes among African Americans. The purpose of the study was to assess the association of adiponectin on type 2 diabetes and hypertension likelihood among African American men and women in the Jackson Heart Study. Methods: Separate multivariate logistic regressions were conducted stratified by sex based on cross-sectional data with type 2 diabetes and hypertension as the outcomes. Adiponectin was divided intofour quartiles with the highest quartile as the reference. Data was collected from 2000-2004 on 3,663 participants. Data analysis was conducted in calendar year 2014. Two- tailed P < .05 was established as level of significance. Results: In the adjusted multivariate models, adiponectin level was inversely associated with type 2 diabetes among women (odds ratio [OR], 95% confidence interval [CI] = 1.47, [1.02, 2.11], P = .04). There was no association among men. Women with the lowest level of adiponectin were less likely to be hypertensive (OR, 95% CI = 0.66, [0.46, 0.95], p = .02). There was no association among men. Conclusion: Findings reveal differential associations between levels of adiponectin with type 2 diabetes and hypertension likelihood among African American women. More research is needed to elucidate this differential association. [ABSTRACT FROM AUTHOR]

Introduction Metabolic syndrome (MetS) is a clustering of five metabolic risk factors including abdominal obesity, elevated blood pressure, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), and impaired fasting glucose. Few studies have fully reported the strength of clustering of these risk factors in a parent-offspring relationship. This analysis describes the associations between parents and their adult offspring in regard to MetS. It also estimates the association between each risk factor in parents and the presence of MetS in their offspring. Methods We analyzed data for 1193 offspring (565 sons, and 628 daughters) from the Framingham Offspring Study who attended examinations 5, 6, and 7. Information about their parents was collected from examinations 13, 14 and 15 of the Framingham Original Cohort study. We used pedigree file to combine parental and offspring's data. Participants were classified as having the MetS according to the Adult Treatment Panel III criteria. Analyses were conducted separately for mothers and fathers. Logistic regression was used to estimate the associations. Results After adjusting for age, education, smoking, alcohol consumption and physical activity level of offspring, no significant association was found between fathers' and their offspring's MetS. Mothers' MetS was significantly and positively associated with their daughters' MetS (adjusted odds ratio or adj OR:1.63; 95% confidence Interval, CI:1.02-2.61), but not with their sons' MetS. When analyzed by individual components, maternal impaired glucose (adj OR:2.03; 95% CI:1.02- 9.31), abdominal obesity (adj OR:1.56; 95% CI:0.98- 2.55) and low HDL-C (adj OR: 2.12; 95% CI:1.36-3.32) were associated daughters' MetS. Maternal low HDL-C and raised total cholesterol showed marginal association with son's MetS. For fathers, only impaired glucose (adj OR:4.91; 95% CI:2.07- 11.68) was associated with their daughters' MetS. Conclusions Using the data from Framingham Heart Study, we demonstrate differential association of MetS and its components between parents and offspring. Mother's MetS was strongly related with daughter's MetS, but the association was inconsistent with son's MetS. No association was found between father's MetS and offspring's Mets. These results provide evidence that daughters with mother's MetS are in higher risk than daughters or sons with father's MetS. [ABSTRACT FROM AUTHOR]