Dataset of allele and genotype frequencies of five polymorphisms candidate genes analyzed for association with body mass index in Russian women.
ABSTRACT: Data on the allele and genotype frequencies of the five single nucleotide polymorphisms (SNPs) 5 genes - rs1514175 TNNI3K, rs713586 RBJ, rs887912 FANCL, rs2241423 MAP2K5, rs12444979 GPRC5B in Russian women are presented. Several genome-wide association studies identified these SNPs could be significant genetic markers associated with body mass index (BMI). Standard methods were used for collecting of the anthropometric characteristics (height and weight). We calculated the frequencies of alleles and genotypes of five SNPs in 5 groups: all samples, underweight (BMI<18.50), normal weight (18.50-24.99), overweight (25.00-29.99), obese (>30.00).
Project description:BACKGROUND:Large-scale genome-wide association studies have identified multiple genetic variants that are associated with elevated body mass index (BMI) or the risk of obesity in Caucasian or Asian populations. We examined whether these variants are individually associated with obesity in Chinese children, and also assessed their cumulative effects and predictive value for obesity risk in Chinese children. METHODS:We genotyped 40 single nucleotide polymorphisms (SNPs) and conducted association analyses for 32/40 SNPs with an estimated minor allele frequency >1% in 2 030 unrelated Chinese children, including 607 normal-weight, 718 overweight, and 705 obese individuals from two cross-sectional study groups. Logistic regression and linear regression under the additive model were used to examine associations, and the area under the receiver operating characteristic curve (AUCROC) was reported as prediction summary. RESULTS:We identified obesity association for 6 SNPs near SEC16B, RBJ, CDKAL1, TFAP2B, MAP2K5 and FTO (odds ratios (ORs) ranged from 1.19 to 1.41, nominal two-sided P-values < 0.05). Association (Bonferroni corrected) of rs543874 near SEC16B and rs2241423 near MAP2K5 had presumably stronger effects on obesity in Chinese children than in Caucasian populations. Their risk alleles were also associated with BMI standard deviation score (BMI-SDS) variability. We demonstrated the cumulative effects of the 32 SNPs on obesity risk (per risk allele: OR = 1.06, 95 % CI: 1.03-1.11, P = 4.84 × 10(-4)) and BMI-SDS (? = 0.04, 95% CI: 0.02-0.06, P = 3.69 × 10(-7)). The difference in AUCROC for a model with covariates (age, age square, sex and study group) and the model including covariates and all 32 SNPs was 2.8% (P = 0.0002). CONCLUSION:While six SNPs were individually associated with obesity in Chinese children, the 32 common variants identified by recent GWA studies had cumulative effects and resulted in a limited increase in the AUCROC predictive value for childhood obesity.
Project description:Highlights • In a large group of subjects without overt conduction system disease, there was a positive association between increasing BMI and electrocardiographic QRS duration that was independent of other covariates such as sex and age.• Females had narrower QRS complex than the males at similar age and in the similar BMI category.• Findings of this research should prompt further studies to explore the underlying mechanisms for these observations and potential reversibility of the conduction abnormality with weight loss <h4>Background</h4> Electrocardiogram (ECG) measured QRS duration has been shown to influence cardiovascular outcomes. However, there is paucity of data on whether ECG QRS duration is influenced by obesity and sex in large populations. <h4>Methods</h4> All ECGs performed by a pathology provider over a 2-year period were included. ECGs with confounding factors and those not in sinus rhythm were excluded from the primary analysis. <h4>Results</h4> Of the 76,220 who met the inclusion criteria, 41,685 (55%) were females. The median age of the study cohort was 61 years (interquartile [IQR] range 48–71 years). The median QRS duration was 86 ms (IQR 80–94 ms). The median BMI was 27.6 kg/m2 (IQR 24.2–31.8 kg/m2). When stratified according to the World Health Organization classification of BMI < 18.50 kg/m2, 18.50–24.99 kg/m2, 25.00–29.99 kg/m2, and ≥ 30.00 kg/m2, the median QRS durations were 82 ms (IQR 76–88 ms), 86 ms (IQR 80–92 ms), 88 ms (IQR 80–94 ms) and 88 ms (IQR 82–94 ms), respectively (p < 0.001 for linear trend). Median QRS duration for females was 84 ms (IQR 78–88 ms); for males, it was 92 ms (IQR 86–98 ms), p < 0.001. Compared to males, females had narrower QRS complexes at similar age and similar BMI. In multiple linear regression analysis, BMI correlated positively with QRS duration (standardized beta 0.095, p < 0.001) independent of age, sex, and heart rate. <h4>Conclusions</h4> In this large cohort there was a positive association between increasing BMI and QRS duration. Females had narrower QRS duration than males at similar age and similar BMI.
Project description:BACKGROUND:Obesity is associated with vascular risk factors that in turn, may increase dementia risk. However, higher body mass index (BMI) in late life may be neuroprotective. The possible neural mechanisms underlying the benefit of higher BMI on cognition in older adults are largely unknown. Thus, we used functional connectivity magnetic resonance imaging (fcMRI) to examine: (1) the relationship between BMI and functional brain connectivity; and (2) the mediating role of functional brain connectivity in the association between baseline BMI and change in cognitive function over a 12-month period. METHODS:We conducted a 12-month, prospective study among 66 community-dwelling older adults, aged 70 to 80 years, who were categorized as: normal weight (BMI from 18.50 to 24.99); overweight (BMI from 25.00 to 29.99); and obese (BMI ? 30.00). At baseline, participants performed a finger-tapping task during fMRI scanning. Relevant neural networks were initially identified through independent component analysis (ICA) and subsequently examined through seed-based functional connectivity analysis. At baseline and 12-months, we measured three executive cognitive processes: (1) response inhibition; (2) set shifting; and (3) working memory. RESULTS:Obese individuals showed lower task-related functional connectivity during finger tapping in the default mode network (DMN) compared with their healthy weight counterparts (p < 0.01). Lower task-related functional connectivity in the DMN at baseline was independently associated with better working memory performance at 12-months (p = 0.02). Finally, DMN functional connectivity during finger tapping significantly mediated the relationship between baseline BMI and working memory at 12-months (indirect effect: -0.155, 95% confidence interval [-0.313, -0.053]). CONCLUSIONS:These findings suggest that functional connectivity of the DMN may be an underlying mechanism by which higher BMI confers protective effects to cognition in late life.
Project description:<h4>Background</h4>Body Mass Index (BMI) is widely regarded as an important clinical trait for obesity and other diseases such as Type 2 diabetes, coronary heart disease, and osteoarthritis.<h4>Methods</h4>This study uses 6,011 samples of genotype data from ethnic Korean subjects. The data was retrieved from the Korea Association Resource. To identify the BMI-related markers within the Korean population, we collected genome-wide association study (GWAS) markers using a GWAS catalog and also obtained other markers from nearby regions. Of the total 6,011 samples, 5,410 subjects were used as part of a single nucleotide polymorphism (SNP) selection set in order to identify the overlapping BMI-associated SNPs within a 10-fold cross validation.<h4>Results</h4>We selected nine SNPs (<i>rs12566985</i> (<i>FPGT-TNNI3K</i>), <i>rs6545809</i> (<i>ADCY3</i>), <i>rs2943634</i> (located near <i>LOC646736</i>), <i>rs734597</i> (located near <i>TFAP2B</i>), <i>rs11030104</i> (<i>BDNF</i>), <i>rs7988412</i> (<i>GTF3A</i>), <i>rs2241423</i> (<i>MAP2K5</i>), <i>rs7202116</i> (<i>FTO</i>), and <i>rs6567160</i> (located near <i>LOC105372152</i>) to assist in BMI prediction. The calculated weighted genetic risk scores based on the selected 9 SNPs within the SNP selection set were applied to the final validation set consisting of 601 samples. Our results showed upward trends in the BMI values (<i>P</i> < 0.0001) within the 10-fold cross validation process for <i>R</i><sup>2</sup> > 0.22. These trends were also observed within the validation set for all subjects, as well as within the validation sets divided by gender (<i>P</i> < 0.0001, <i>R</i><sup>2</sup> > 0.46).<h4>Discussion</h4>The set of nine SNPs identified in this study may be useful for prospective predictions of BMI.
Project description:BACKGROUND:Obesity is an epidemic in New York City, the global epicenter of the coronavirus pandemic. Previous studies suggest that obesity is a possible risk factor for adverse outcomes in COVID-19. OBJECTIVE:To elucidate the association between obesity and COVID-19 outcomes. DESIGN:Retrospective cohort study of COVID-19 hospitalized patients tested between March 10 and April 13, 2020. SETTING:SUNY Downstate Health Sciences University, a COVID-only hospital in New York. PARTICIPANTS:In total, 684 patients were tested for COVID-19 and 504 were analyzed. Patients were categorized into three groups by BMI: normal (BMI 18.50-24.99), overweight (BMI 25.00-29.99), and obese (BMI???30.00). MEASUREMENTS:Primary outcome was 30-day in-hospital mortality, and secondary outcomes were intubation, acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), and acute cardiac injury (ACI). RESULTS:There were 139 patients (27%) with normal BMI, 150 patients who were overweight (30%), and 215 patients with obesity (43%). After controlling for age, gender, diabetes, hypertension, and qSOFA score, there was a significantly increased risk of mortality in the overweight (RR 1.4, 95% CI 1.1-1.9) and obese groups (RR 1.3, 95% CI 1.0-1.7) compared with those with normal BMI. Similarly, there was a significantly increased relative risk for intubation in the overweight (RR 2.0, 95% CI 1.2-3.3) and obese groups (RR 2.4, 95% CI 1.5-4.0) compared with those with normal BMI. Obesity did not affect rates of AKI, ACI, or ARDS. Furthermore, obesity appears to significantly increase the risk of mortality in males (RR 1.4, 95% CI 1.0-2.0, P?=?0.03), but not in females (RR 1.2, 95% CI 0.77-1.9, P?=?0.40). CONCLUSION:This study reveals that patients with overweight and obesity who have COVID-19 are at increased risk for mortality and intubation compared to those with normal BMI. These findings support the hypothesis that obesity is a risk factor for COVID-19 complications and should be a consideration in management of COVID-19.
Project description:Recent genome-wide association studies have identified a single nucleotide polymorphism within the last intron of MAP2K5 associated with a higher body mass index (BMI) in adults. MAP2K5 is a component of the MAPK-family intracellular signaling pathways, responding to extracellular growth factors such as brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF). In this study, we examined the association of this variant in two cohorts of children from Sweden and Greece.We examine the association of rs2241423 to BMI in a cohort of 474 Swedish children admitted for treatment of childhood obesity and 519 children matched for gender, ethnicity and socioeconomic background from the Stockholm area, as well as a cross-sectional cohort of 2308 Greek school children (Healthy Growth Study). Children were genotyped using a predesigned TaqMan polymorphism assay. Logistic regression was used to test for an association of rs2241423 to obesity in the cohort of Swedish children. Linear regression was used to test for an association of rs2241423 to BMI z-score and phenotypic measurements of body adiposity in the cohort of Greek children. Models were adjusted for age and gender. In the cohort of Greek children the model was also adjusted for stage of pubertal development.The minor allele of rs2241423, allele A, was associated with a protective effect against obesity in the cohort of Swedish children (p = 0.029, OR = 0.79 (95% CI: 0.64-0.98)), and with a lower BMI z-score in the cohort of Greek children (p = 0.028, ? =?-0.092). No association to phenotypic measurements of body fat distribution could be observed in our study.rs2241423 was associated with BMI and obesity in two independent European cohorts suggesting a role for MAP2K5 in early weight regulation.
Project description:Genome-wide association studies (GWAS) have identified multiple common variants associated with body mass index (BMI). In this study, we tested 23 genotyped GWAS-significant SNPs (p-value<5*10-8) for longitudinal associations with BMI during childhood (3-17 years) and adulthood (18-45 years) for 658 subjects. We also proposed a heuristic forward search for the best joint effect model to explain the longitudinal BMI variation. After using false discovery rate (FDR) to adjust for multiple tests, childhood and adulthood BMI were found to be significantly associated with six SNPs each (q-value<0.05), with one SNP associated with both BMI measurements: KCTD15 rs29941 (q-value<7.6*10-4). These 12 SNPs are located at or near genes either expressed in the brain (BDNF, KCTD15, TMEM18, MTCH2, and FTO) or implicated in cell apoptosis and proliferation (FAIM2, MAP2K5, and TFAP2B). The longitudinal effects of FAIM2 rs7138803 on childhood BMI and MAP2K5 rs2241423 on adulthood BMI decreased as age increased (q-value<0.05). The FTO candidate SNPs, rs6499640 at the 5 '-end and rs1121980 and rs8050136 downstream, were associated with childhood and adulthood BMI, respectively, and the risk effects of rs6499640 and rs1121980 increased as birth weight decreased. The best joint effect model for childhood and adulthood BMI contained 14 and 15 SNPs each, with 11 in common, and the percentage of explained variance increased from 0.17% and 9.0*10(-6)% to 2.22% and 2.71%, respectively. In summary, this study evidenced the presence of long-term major effects of genes on obesity development, implicated in pathways related to neural development and cell metabolism, and different sets of genes associated with childhood and adulthood BMI, respectively. The gene effects can vary with age and be modified by prenatal development. The best joint effect model indicated that multiple variants with effects that are weak or absent alone can nevertheless jointly exert a large longitudinal effect on BMI.
Project description:High early morbidity and mortality following antiretroviral therapy (ART) initiation has been a distinguishing feature of ART programmes in resource limited settings (RLS) compared to high-income countries. This study assessed how well body mass index (BMI: kg/m2) correlated with survival among HIV infected patients with and without TB co-infection.We retrospectively evaluated clinical data from 1000 HIV infected patients, among whom 389 were also co-infected with TB, between January 2008 and December 2010, in KwaZulu-Natal, South Africa.Among 948 patients eligible for analysis, 15.7% (149/948) were underweight (<?18.50), 55.9% (530/948) had normal BMI (?18.50-24.90), 18.7% (177/948) were overweight (25.00-29.00) and 9.7% (92/948) were obese (?30.00). Irrespective of TB status, underweight patients, had significantly higher risk of death compared to those with normal BMI at baseline (aHR?=?2.9; 95% CI: 1.5-5.7; P?=?0.002).Irrespective of TB co-infection, low BMI correlated with mortality in HIV infected patients.UKZN Biomedical Research Ethics Committee Reference number E 248/05, 23 September 2005.
Project description:Genome-wide association studies (GWAS) have identified consistent associations with obesity. However, the mechanisms remain unclear.The objective was to determine the association between obesity susceptibility loci and dietary intake.The association of GWAS-identified obesity risk alleles (FTO, MC4R, SH2B1, BDNF, INSIG2, TNNI3K, NISCH-STAB1, MTIF3, MAP2K5, QPCTL/GIPR, and PPARG) with dietary intake, measured through food-frequency questionnaires, was investigated in 2075 participants from the Look AHEAD (Action for Health in Diabetes) clinical trial. We adjusted for age, sex, population stratification, and study site.Obesity risk alleles at FTO rs1421085 significantly predicted more eating episodes per day (P = 0.001)-an effect that persisted after adjustment for body weight (P = 0.004). Risk variants within BDNF were significantly associated with more servings from the dairy product and the meat, eggs, nuts, and beans food groups (P ? 0.004). The risk allele at SH2B1 rs4788099 was significantly associated with more servings of dairy products (P = 0.001), whereas the risk allele at TNNI3K rs1514176 was significantly associated with a lower percentage of energy from protein (P = 0.002).These findings suggest that obesity risk loci may affect the pattern and content of food consumption among overweight or obese individuals with type 2 diabetes. The Look AHEAD Genetic Ancillary Study was registered at clinicaltrials.gov as NCT01270763 and the Look AHEAD study as NCT00017953.
Project description:Objective:Restless legs syndrome (RLS) is considered a genetic disease and, following a genome-wide association study conducted in 2007, the mitogen-activated protein kinase 5 (MAP2K5) gene has been regarded as the promising candidate gene for RLS. The present study investigated whether polymorphisms of MAP2K5 are associated with antipsychotics-induced RLS in schizophrenia. Methods:We assessed antipsychotics-induced RLS symptoms in 190 Korean schizophrenic patients using the diagnostic criteria of the International Restless Legs Syndrome Study Group. Five single-nucleotide polymorphisms (SNPs) of MAP2K5 were genotyped. We investigated genetic and haplotypic associations of these five SNPs with the risk of antipsychotics-induced RLS symptoms. Results:We divided the 190 subjects into 2 groups: 1) those with RLS symptoms (n=96) and 2) those without RLS symptoms (n=94). There were no significant intergroup differences in the distributions of the genotypes and alleles of the rs1026732, rs11635424, rs12593813, rs4489954, and rs3784709 SNPs. However, the haplotype analysis showed that the G-G-G-G-T (rs1026732-rs11635424-rs12593813-rs4489954-rs3784709) haplotype was associated with RLS symptoms (permutation p=0.033). Conclusion:These data suggest that a haplotype of MAP2K5 polymorphisms confers increased susceptibility to antipsychotics-induced RLS symptoms in schizophrenic patients.