Dataset Information

A multilocus genetic risk score for obesity: Association with BMI and metabolic alterations in a cohort with severe obesity.

ABSTRACT: Genome wide association studies have identified numerous single nucleotide polymorphisms (SNPs) associated with obesity, yet effect sizes of individual SNPs are small. Therefore, the aim of our study was to investigate whether a genetic risk score (GRS) comprising risk alleles of SNPs identified in the GIANT consortium meta-analyses shows association with body mass index (BMI) and other BMI related metabolic alterations in a cohort with an extreme phenotype. Genotyping of 93 SNPs was performed in 314 obese individuals (mean BMI 40.5 ± 7.8 kg/m², aged 45 ± 12 years), participating in a standardized weight reduction program, and in 74 lean controls (mean BMI 24.6 ± 3.3 kg/m², aged 41.7 ± 13.4 years). Allele numbers of all 93 SNPs were added to a GRS. Anthropometric parameters, parameters of glucose/insulin and lipid metabolism were assessed standardized after a 12 hours fast. GRS was significantly different between controls and obese individuals (unweighted GRS: 86.6 vs 89.0, P = .002; weighted GRS: 84.9 vs 88.3, P = .005). Furthermore, linear regression analysis showed significant associations of GRS with BMI ( P < .0001), weight ( P = .0005), waist circumference ( P = .0039), fat mass ( P < .0001) and epicardial fat thickness ( P = .0032), yet with small effect sizes ( r ² < 0.06). In conclusion, in our study GRS could differentiate between extreme obese and lean individuals, and was associated with BMI and its related traits, yet with small effect sizes.

SUBMITTER: Sag SJM

PROVIDER: S-EPMC10419793 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A multilocus genetic risk score for obesity: Association with BMI and metabolic alterations in a cohort with severe obesity.

Sag Sabine Julia Maria SJM Mueller Stephanie S Wallner Stefan S Strack Christina C Hubauer Ute U Mohr Margareta M Zeller Judith J Loew Thomas T Rehli Michael M Wimmer Julia J Zimmermann Martina Erika ME Maier Lars Siegfried LS Fischer Marcus M Baessler Andrea A

Medicine 20230801 32

Genome wide association studies have identified numerous single nucleotide polymorphisms (SNPs) associated with obesity, yet effect sizes of individual SNPs are small. Therefore, the aim of our study was to investigate whether a genetic risk score (GRS) comprising risk alleles of SNPs identified in the GIANT consortium meta-analyses shows association with body mass index (BMI) and other BMI related metabolic alterations in a cohort with an extreme phenotype. Genotyping of 93 SNPs was performed i ...[more]

PMID: 37565910

Similar Datasets

Project description:We will explore the genetic (including APC, k-ras, p53, MSI, etc.) and environmental (including family history, life style, diet, nutritional status, DM, serum IGF-I, IGFBP-3, etc.) risk factors of colorectal tumorigenesis. We will accrue approximately 1000 patients as experimental group. The control group consists of 2000 individuals who were confirmed without colorectal cancer or polyps by colonoscopy. We estimated the statistical power of this study will reach more than 90%. In the second year, we will explore the association between various environmental risk factors with the epigenetic changes of various oncogenes and tumor suppressor genes. Firstly, we will study the correlation between hypermethylation of promoter region of hMLH1 gene with various environmental factors. Next, we will explore the genetic polymorphisms of promoter of E-cadherin gene. Recently, it has been reported that the C→A genetic polymorphism in the promoter region of E-cadherin gene in prostate cancer. Since this phenomenon has not been reported in colorectal cancer, it is mandatory for us to extend our research to the E-cadherin polymorphisms of colorectal cancer. Moreover, this project will focus on exploration of the association between the genetic polymorphisms of promoter of TS gene with chemosensitivity to 5-Fu-based therapy. We speculated that the better prognosis in colorectal tumors with MSI is related to their expression of TS gene. In summary, the second year of this project will extend our accumulated experience in the study of genetic polymorphisms to further clarify the association between genetic polymorphisms of TS gene with the prognosis of colorectal cancers after chemotherapy. We believe that this project will facilitate: (1) the further clarification of colorectal cancer tumorigenesis; (2) the establishment of domestic epidemiological data of colorectal cancer of Taiwan, and (3) the improvement of the quality of clinical management of patients with colorectal cancer.

Project description:Comparison of patients with coronary heart disease and controls in genome-wide association studies has revealed several single nucleotide polymorphisms (SNPs) associated with coronary heart disease. We aimed to establish the external validity of these findings and to obtain more precise risk estimates using a prospective cohort design.We tested 13 recently discovered SNPs for association with coronary heart disease in a case-control design including participants differing from those in the discovery samples (3829 participants with prevalent coronary heart disease and 48,897 controls free of the disease) and a prospective cohort design including 30,725 participants free of cardiovascular disease from Finland and Sweden. We modelled the 13 SNPs as a multilocus genetic risk score and used Cox proportional hazards models to estimate the association of genetic risk score with incident coronary heart disease. For case-control analyses we analysed associations between individual SNPs and quintiles of genetic risk score using logistic regression.In prospective cohort analyses, 1264 participants had a first coronary heart disease event during a median 10·7 years' follow-up (IQR 6·7-13·6). Genetic risk score was associated with a first coronary heart disease event. When compared with the bottom quintile of genetic risk score, participants in the top quintile were at 1·66-times increased risk of coronary heart disease in a model adjusting for traditional risk factors (95% CI 1·35-2·04, p value for linear trend=7·3×10(-10)). Adjustment for family history did not change these estimates. Genetic risk score did not improve C index over traditional risk factors and family history (p=0·19), nor did it have a significant effect on net reclassification improvement (2·2%, p=0·18); however, it did have a small effect on integrated discrimination index (0·004, p=0·0006). Results of the case-control analyses were similar to those of the prospective cohort analyses.Using a genetic risk score based on 13 SNPs associated with coronary heart disease, we can identify the 20% of individuals of European ancestry who are at roughly 70% increased risk of a first coronary heart disease event. The potential clinical use of this panel of SNPs remains to be defined.The Wellcome Trust; Academy of Finland Center of Excellence for Complex Disease Genetics; US National Institutes of Health; the Donovan Family Foundation.

Project description:Genes involved in the regulation of catecholamine function may be important in obesity because of the role catecholamines play in energy expenditure and lipolysis. To determine if common single nucleotide polymorphisms (SNPs) in beta(1)-adrenergic receptor (ADRB1), beta(2)-adrenergic receptor (ADRB2), beta(3)-adrenergic receptor (ADRB3), and alpha(2)-adrenergic receptor (ADRA2A) genes associate with obesity and metabolic alterations, we recruited 74 healthy African American and 161 white men and women (age, 18-49 years) to participate in this case-control genetic association study. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism. Associations between genotype and body mass index (BMI), percentage of body fat (by measuring skinfold thickness in 7 different sites), fasting (12-hour) plasma glucose, insulin, potassium concentrations, glycated hemoglobin, and insulin resistance (homeostasis model assessment [HOMA(IR)] score) were performed. Among whites, the ADRB1 Arg389-->Gly variant associated with insulin concentrations and HOMA(IR): mean +/- SD values for insulin and HOMA(IR) in Arg389 homozygotes and carriers of the Gly were 10 +/- 7.0 and 12 +/- 9.4 micro IU/mL (P = .02) and 2.1 +/- 1.7 and 2.6 +/- 2.2 (P = .057), respectively. Systolic blood pressure was higher in whites for carriers of the ADBR1 Ser49 compared to Gly49 homozygotes (124 +/- 12.6 vs 119 +/- 11.3 mm Hg, respectively; P = .02). Subsequent analysis revealed that these associations were attributable to a higher BMI among obese participants. The ADRA2A G1780A SNP associated with BMI and percentage of body fat in African Americans (P = .05). Interactions were detected between ADRA2A C-1291G and ADRB2 Gln27-->Glu variants for obesity in African Americans and between ADRA2A C-1291G SNP and ADBR1 haplotype for obesity in whites. We conclude that common SNPs in adrenergic receptor genes may be important susceptibility loci for obesity and related alterations. Because of the limited size of our populations, our results should be interpreted with caution and should be replicated in larger populations.

Project description:BackgroundThe metabolic score for visceral fat (METS-VF) is a recently identified index for evaluating visceral fat, also referred to as abdominal obesity. The skeletal muscle mass index (SMI) serves as a critical measure for assessing muscle mass and sarcopenia. Both obesity and the reduction of muscle mass can significantly affect human health. However, research exploring the relationship between METS-VF and SMI remains limited. This study aims to investigate whether a association exists between these two indices, and if so, to elucidate the nature of their interactions.MethodsWe conducted a cross-sectional study using data from the NHANES database, focusing on U.S. adults aged 20 years and older from 2013 to 2018. Controlling for relevant covariables, we primarily investigated the association between METS-VF and SMI values utilizing weighted multivariable linear regression models. Additionally, we assessed the diagnostic efficacy of METS-VF for sarcopenia.ResultsA total of 3,594 participants were included in this study for analysis. The final adjusted model from the weighted multivariable linear regression indicated that METS-VF was negatively associated with SMI, with a coefficient of β = -0.13 (95% CI: -0.14, -0.12; P < 0.001). Subgroup analyses further demonstrated that this negative association was consistent across different populations. Notably, the negative association varied significantly between diabetic and nondiabetic population, as well as among populations classified by different BMI categories. Additionally, threshold effect analysis identified a significant inflection knot at 6.33. The characteristic curves of the subjects' work illustrated that, compared to other indicators, METS-VF exhibited excellent diagnostic efficacy for sarcopenia, with an area under the curve (AUC) of 0.825.ConclusionOur results indicate that METS-VF is negatively correlated with SMI among adults in the United States, suggesting that visceral obesity exerts a detrimental effect on muscle mass. Furthermore, METS-VF shows potential as a valuable indicator for assessing SMI and sarcopenia. These findings underscore the importance of considering lipid metabolism disorders in the context of muscle health and highlight the potential for developing prevention strategies for sarcopenia.

Dataset Information

A multilocus genetic risk score for obesity: Association with BMI and metabolic alterations in a cohort with severe obesity.

Publications

A multilocus genetic risk score for obesity: Association with BMI and metabolic alterations in a cohort with severe obesity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets