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/m2, 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 rese...
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| Format: | Online |
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Public Library of Science
2013
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737377/ |
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pubmed-37373772013-08-15 Contribution of 32 GWAS-Identified Common Variants to Severe Obesity in European Adults Referred for Bariatric Surgery Mägi, Reedik Manning, Sean Yousseif, Ahmed Pucci, Andrea Santini, Ferruccio Karra, Efthimia Querci, Giorgia Pelosini, Caterina McCarthy, Mark I. Lindgren, Cecilia M. Batterham, Rachel L. Research Article The prevalence of severe obesity, defined as body mass index (BMI) ≥35.0 kg/m2, 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/m2) 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/m2); 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. Public Library of Science 2013-08-07 /pmc/articles/PMC3737377/ /pubmed/23950990 http://dx.doi.org/10.1371/journal.pone.0070735 Text en © 2013 Mägi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Mägi, Reedik Manning, Sean Yousseif, Ahmed Pucci, Andrea Santini, Ferruccio Karra, Efthimia Querci, Giorgia Pelosini, Caterina McCarthy, Mark I. Lindgren, Cecilia M. Batterham, Rachel L. |
| spellingShingle |
Mägi, Reedik Manning, Sean Yousseif, Ahmed Pucci, Andrea Santini, Ferruccio Karra, Efthimia Querci, Giorgia Pelosini, Caterina McCarthy, Mark I. Lindgren, Cecilia M. Batterham, Rachel L. Contribution of 32 GWAS-Identified Common Variants to Severe Obesity in European Adults Referred for Bariatric Surgery |
| author_facet |
Mägi, Reedik Manning, Sean Yousseif, Ahmed Pucci, Andrea Santini, Ferruccio Karra, Efthimia Querci, Giorgia Pelosini, Caterina McCarthy, Mark I. Lindgren, Cecilia M. Batterham, Rachel L. |
| author_sort |
Mägi, Reedik |
| title |
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_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_sort |
contribution of 32 gwas-identified common variants to severe obesity in european adults referred for bariatric surgery |
| description |
The prevalence of severe obesity, defined as body mass index (BMI) ≥35.0 kg/m2, 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/m2) 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/m2); 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. |
| publisher |
Public Library of Science |
| publishDate |
2013 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737377/ |
| _version_ |
1612001625465946112 |