Contribution of 32 GWAS-identified common variants to severe obesity in European adults referred for bariatric surgery.
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 r...
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0070735&type=printable |
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| author | Reedik Mägi Sean Manning Ahmed Yousseif Andrea Pucci Ferruccio Santini Efthimia Karra Giorgia Querci Caterina Pelosini Mark I McCarthy Cecilia M Lindgren Rachel L Batterham |
| author_facet | Reedik Mägi Sean Manning Ahmed Yousseif Andrea Pucci Ferruccio Santini Efthimia Karra Giorgia Querci Caterina Pelosini Mark I McCarthy Cecilia M Lindgren Rachel L Batterham |
| author_sort | Reedik Mägi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-81daa3778f2c4b2b88e802f4565aa0b0 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-81daa3778f2c4b2b88e802f4565aa0b02025-08-20T03:10:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7073510.1371/journal.pone.0070735Contribution of 32 GWAS-identified common variants to severe obesity in European adults referred for bariatric surgery.Reedik MägiSean ManningAhmed YousseifAndrea PucciFerruccio SantiniEfthimia KarraGiorgia QuerciCaterina PelosiniMark I McCarthyCecilia M LindgrenRachel L BatterhamThe 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0070735&type=printable |
| spellingShingle | Reedik Mägi Sean Manning Ahmed Yousseif Andrea Pucci Ferruccio Santini Efthimia Karra Giorgia Querci Caterina Pelosini Mark I McCarthy Cecilia M Lindgren Rachel L Batterham Contribution of 32 GWAS-identified common variants to severe obesity in European adults referred for bariatric surgery. PLoS ONE |
| title | Contribution of 32 GWAS-identified common variants to severe obesity in European adults referred for bariatric surgery. |
| title_full | Contribution of 32 GWAS-identified common variants to severe obesity in European adults referred for bariatric surgery. |
| title_fullStr | Contribution of 32 GWAS-identified common variants to severe obesity in European adults referred for bariatric surgery. |
| title_full_unstemmed | Contribution of 32 GWAS-identified common variants to severe obesity in European adults referred for bariatric surgery. |
| title_short | Contribution of 32 GWAS-identified common variants to severe obesity in European adults referred for bariatric surgery. |
| title_sort | contribution of 32 gwas identified common variants to severe obesity in european adults referred for bariatric surgery |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0070735&type=printable |
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