Dataset Information

Contribution of 32 GWAS-identified common variants to severe obesity in European adults referred for bariatric surgery.

ABSTRACT: The prevalence of severe obesity, defined as body mass index (BMI) ? 35.0 kg/m(2), is rising rapidly. Given the disproportionately high health burden and healthcare costs associated with this condition, understanding the underlying aetiology, including predisposing genetic factors, is a biomedical research priority. Previous studies have suggested that severe obesity represents an extreme tail of the population BMI variation, reflecting shared genetic factors operating across the spectrum. Here, we sought to determine whether a panel of 32 known common obesity-susceptibility variants contribute to severe obesity in patients (n = 1,003, mean BMI 48.4 ± 8.1 kg/m(2)) attending bariatric surgery clinics in two European centres. We examined the effects of these 32 common variants on obesity risk and BMI, both as individual markers and in combination as a genetic risk score, in a comparison with normal-weight controls (n = 1,809, BMI 18.0-24.9 kg/m(2)); an approach which, to our knowledge, has not been previously undertaken in the setting of a bariatric clinic. We found strong associations with severe obesity for SNP rs9939609 within the FTO gene (P = 9.3 × 10(-8)) and SNP rs2815752 near the NEGR1 gene (P = 3.6 × 10(-4)), and directionally consistent nominal associations (P<0.05) for 12 other SNPs. The genetic risk score associated with severe obesity (P = 8.3 × 10(-11)) but, within the bariatric cohort, this score did not associate with BMI itself (P = 0.264). Our results show significant effects of individual BMI-associated common variants within a relatively small sample size of bariatric patients. Furthermore, the burden of such low-penetrant risk alleles contributes to severe obesity in this population. Our findings support that severe obesity observed in bariatric patients represents an extreme tail of the population BMI variation. Moreover, future genetic studies focused on bariatric patients may provide valuable insights into the pathogenesis of obesity at a population level.

SUBMITTER: Magi R

PROVIDER: S-EPMC3737377 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Contribution of 32 GWAS-identified common variants to severe obesity in European adults referred for bariatric surgery.

Mägi Reedik R Manning Sean S Yousseif Ahmed A Pucci Andrea A Santini Ferruccio F Karra Efthimia E Querci Giorgia G Pelosini Caterina C McCarthy Mark I MI Lindgren Cecilia M CM Batterham Rachel L RL

PloS one 20130807 8

The prevalence of severe obesity, defined as body mass index (BMI) ≥ 35.0 kg/m(2), is rising rapidly. Given the disproportionately high health burden and healthcare costs associated with this condition, understanding the underlying aetiology, including predisposing genetic factors, is a biomedical research priority. Previous studies have suggested that severe obesity represents an extreme tail of the population BMI variation, reflecting shared genetic factors operating across the spectrum. Here, ...[more]

PMID: 23950990

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Project description:ImportanceBariatric surgery can resolve hyperlipidemia, cardiovascular disease, and diabetes, but the long-term postoperative trajectories of medications for these conditions are unknown.ObjectiveTo clarify the long-term use of lipid-lowering, cardiovascular, and antidiabetic medication after bariatric surgery compared with no surgery for morbid obesity.Design, setting, and participantsThis population-based cohort study took place in Sweden (2005-2020) and Finland (1995-2018) and included individuals diagnosed with obesity. Analysis took place between July 2021 and January 2022.ExposuresBariatric surgery (gastric bypass or sleeve gastrectomy) patients using lipid-lowering, cardiovascular, or antidiabetic medication were compared with 5 times as many control patients with an obesity diagnosis treated with no surgery, matched for country, age, sex, calendar year, and medication use.Main outcomes and measuresProportions with 95% CIs of lipid-lowering, cardiovascular, or antidiabetic medication.ResultsA total of 26 396 patients underwent bariatric surgery (with gastric bypass or sleeve gastrectomy) (17 521 [66.4%] women; median [IQR] age, 50 [43-56] years) and 131 980 matched control patients (87 605 [66.4%%] women; median [IQR] age, 50 [43-56] years) were included. The proportion of lipid-lowering medication after bariatric surgery decreased from 20.3% (95% CI, 20.2%-20.5%) at baseline to 12.9% (95% CI, 12.7%-13.0%) after 2 years and 17.6% (95% CI, 13.3%-21.8%) after 15 years, while it increased in the no surgery group from 21.0% (95% CI, 20.9%-21.1%) at baseline to 44.6% (95% CI, 41.7%-47.5%) after 15 years. Cardiovascular medications were used by 60.2% (95% CI, 60.0%-60.5%) of bariatric surgery patients at baseline, decreased to 43.2% (95% CI, 42.9%-43.4%) after 2 years, and increased to 74.6% (95% CI, 65.8%-83.4%) after 15 years, while it increased in the no surgery group from 54.4% (95% CI, 54.3%-54.5%) at baseline to 83.3% (95% CI, 79.3%-87.3%) after 15 years. Antidiabetic medications were used by 27.7% (95% CI, 27.6%-27.9%) in the bariatric surgery group at baseline, decreased to 10.0% (95% CI, 9.9%-10.2%) after 2 years, and increased to 23.5% (95% CI, 18.5%-28.5%) after 15 years, while it increased in the no surgery group from 27.7% (95% CI, 27.6%-27.7%) at baseline to 54.2% (95% CI, 51.0%-57.5%) after 15 years.Conclusions and relevanceIn this study, undergoing bariatric surgery was associated with a substantial and long-lasting reduction in the use of lipid-lowering and antidiabetic medications compared with no surgery for obesity, while for cardiovascular medications this reduction was only transient.

Dataset Information

Contribution of 32 GWAS-identified common variants to severe obesity in European adults referred for bariatric surgery.

Publications

Contribution of 32 GWAS-identified common variants to severe obesity in European adults referred for bariatric surgery.

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