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Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples

Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples
Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples
Background
Meta-analysis of case–control genome-wide association studies (GWAS) for early onset and morbid obesity identified four variants in/near the PRL, PTER, MAF and NPC1 genes.

Objective
We aimed to validate association of these variants with obesity-related traits in population-based samples.

Design
Genotypes and anthropometric traits were available in up to 31?083 adults from the Fenland, EPIC-Norfolk, Whitehall II, Ely and Hertfordshire studies and in 2042 children and adolescents from the European Youth Heart Study. In each study, we tested associations of rs4712652 (near-PRL), rs10508503 (near-PTER), rs1424233 (near-MAF) and rs1805081 (NPC1), or proxy variants (r 2>0.8), with the odds of being overweight and obese, as well as with body mass index (BMI), percentage body fat (%BF) and waist circumference (WC). Associations were adjusted for sex, age and age2 in adults and for sex, age, age group, country and maturity in children and adolescents. Summary statistics were combined using fixed effects meta-analysis methods.

Results
We had 80% power to detect odds ratios of 1.046 to 1.092 for overweight and 1.067 to 1.136 for obesity. Variants near PRL, PTER and MAF were not associated with the odds of being overweight or obese, or with BMI, %BF or WC after meta-analysis (P>0.15). The NPC1 variant rs1805081 showed some evidence of association with %BF (?=0.013?s.d./allele, P=0.040), but not with any of the remaining obesity-related traits (P>0.3).

Conclusion
Overall, these variants, which were identified in a GWAS for early onset and morbid obesity, do not seem to influence obesity-related traits in the general population.
0307-0565
191-196
den Hoed, M.
cf30eec5-85a3-4123-aa03-9e64def5a90e
Luan, J.
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Lagenberg, C.
3c5f6325-681c-427e-ae50-cc9e370ef8e0
Cooper, C.
e05f5612-b493-4273-9b71-9e0ce32bdad6
Sayer, A.A.
fb4c2053-6d51-4fc1-9489-c3cb431b0ffb
Jameson, K.
d5fb142d-06af-456e-9016-17497f94e9f2
Kumari, M.
b5ac445e-8cbd-4f37-a99e-630bf0e9b600
Kivimaki, M.
87a6c408-c8b5-48dc-b2c0-e1f425b91dc6
Hingorani, A.D.
92c144ea-f0cc-4556-9786-37def77310d6
Grontved, A.
49b09aba-e6fa-45ab-b52c-2cc75f4d4b6e
Khaw, K.T.
fcf47d76-59c6-4542-80e6-0843eca4ad8c
Ekelund, U.
c93d220c-728d-43e3-900a-3c4f4ca502ff
Wareham, N.J.
7765cb0f-cc0c-4e64-b410-25dfde09806b
Loos, R.J.
e9da5ec5-9d93-4c6c-8947-7469fb4271a7
den Hoed, M.
cf30eec5-85a3-4123-aa03-9e64def5a90e
Luan, J.
3e375ba4-8172-490d-a325-952a118eda53
Lagenberg, C.
3c5f6325-681c-427e-ae50-cc9e370ef8e0
Cooper, C.
e05f5612-b493-4273-9b71-9e0ce32bdad6
Sayer, A.A.
fb4c2053-6d51-4fc1-9489-c3cb431b0ffb
Jameson, K.
d5fb142d-06af-456e-9016-17497f94e9f2
Kumari, M.
b5ac445e-8cbd-4f37-a99e-630bf0e9b600
Kivimaki, M.
87a6c408-c8b5-48dc-b2c0-e1f425b91dc6
Hingorani, A.D.
92c144ea-f0cc-4556-9786-37def77310d6
Grontved, A.
49b09aba-e6fa-45ab-b52c-2cc75f4d4b6e
Khaw, K.T.
fcf47d76-59c6-4542-80e6-0843eca4ad8c
Ekelund, U.
c93d220c-728d-43e3-900a-3c4f4ca502ff
Wareham, N.J.
7765cb0f-cc0c-4e64-b410-25dfde09806b
Loos, R.J.
e9da5ec5-9d93-4c6c-8947-7469fb4271a7

den Hoed, M., Luan, J., Lagenberg, C., Cooper, C., Sayer, A.A., Jameson, K., Kumari, M., Kivimaki, M., Hingorani, A.D., Grontved, A., Khaw, K.T., Ekelund, U., Wareham, N.J. and Loos, R.J. (2013) Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples. International Journal of Obesity, 37 (2), 191-196. (doi:10.1038/ijo.2012.34). (PMID:22430306)

Record type: Article

Abstract

Background
Meta-analysis of case–control genome-wide association studies (GWAS) for early onset and morbid obesity identified four variants in/near the PRL, PTER, MAF and NPC1 genes.

Objective
We aimed to validate association of these variants with obesity-related traits in population-based samples.

Design
Genotypes and anthropometric traits were available in up to 31?083 adults from the Fenland, EPIC-Norfolk, Whitehall II, Ely and Hertfordshire studies and in 2042 children and adolescents from the European Youth Heart Study. In each study, we tested associations of rs4712652 (near-PRL), rs10508503 (near-PTER), rs1424233 (near-MAF) and rs1805081 (NPC1), or proxy variants (r 2>0.8), with the odds of being overweight and obese, as well as with body mass index (BMI), percentage body fat (%BF) and waist circumference (WC). Associations were adjusted for sex, age and age2 in adults and for sex, age, age group, country and maturity in children and adolescents. Summary statistics were combined using fixed effects meta-analysis methods.

Results
We had 80% power to detect odds ratios of 1.046 to 1.092 for overweight and 1.067 to 1.136 for obesity. Variants near PRL, PTER and MAF were not associated with the odds of being overweight or obese, or with BMI, %BF or WC after meta-analysis (P>0.15). The NPC1 variant rs1805081 showed some evidence of association with %BF (?=0.013?s.d./allele, P=0.040), but not with any of the remaining obesity-related traits (P>0.3).

Conclusion
Overall, these variants, which were identified in a GWAS for early onset and morbid obesity, do not seem to influence obesity-related traits in the general population.

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More information

e-pub ahead of print date: 20 March 2012
Published date: February 2013
Organisations: Faculty of Health Sciences

Identifiers

Local EPrints ID: 349214
URI: http://eprints.soton.ac.uk/id/eprint/349214
ISSN: 0307-0565
PURE UUID: 4807b4b6-b3fd-4398-81d3-0645a8db9ed3
ORCID for C. Cooper: ORCID iD orcid.org/0000-0003-3510-0709

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Date deposited: 26 Feb 2013 15:12
Last modified: 18 Mar 2024 02:45

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Contributors

Author: M. den Hoed
Author: J. Luan
Author: C. Lagenberg
Author: C. Cooper ORCID iD
Author: A.A. Sayer
Author: K. Jameson
Author: M. Kumari
Author: M. Kivimaki
Author: A.D. Hingorani
Author: A. Grontved
Author: K.T. Khaw
Author: U. Ekelund
Author: N.J. Wareham
Author: R.J. Loos

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