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

M den Hoed, J Luan, C Langenberg, C Cooper, A A Sayer, K Jameson, M Kumari, M Kivimaki, A D Hingorani, Anders Grøntved, K-T Khaw, U Ekelund, N J Wareham, R J F Loos

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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 age(2) 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 (β=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.

OriginalsprogEngelsk
TidsskriftInternational Journal of Obesity
Vol/bind37
Udgave nummer2
Sider (fra-til)191-6
ISSN0307-0565
DOI
StatusUdgivet - feb. 2013

Fingeraftryk

Morbid Obesity
Genome-Wide Association Study
Meta-Analysis
Population
Body Mass Index
Proxy
Adipose Tissue
Age Groups
Alleles
Odds Ratio

Citer dette

den Hoed, M., Luan, J., Langenberg, C., Cooper, C., Sayer, A. A., Jameson, K., ... Loos, R. J. F. (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), 191-6. https://doi.org/10.1038/ijo.2012.34
den Hoed, M ; Luan, J ; Langenberg, C ; Cooper, C ; Sayer, A A ; Jameson, K ; Kumari, M ; Kivimaki, M ; Hingorani, A D ; Grøntved, Anders ; Khaw, K-T ; Ekelund, U ; Wareham, N J ; Loos, R J F. / Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples. I: International Journal of Obesity. 2013 ; Bind 37, Nr. 2. s. 191-6.
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title = "Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples",
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 age(2) 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 (β=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.",
keywords = "Adolescent, Adult, Age of Onset, Body Mass Index, Carrier Proteins, Case-Control Studies, Child, England, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Membrane Glycoproteins, Middle Aged, Obesity, Morbid, Odds Ratio, Phenotype, Polymorphism, Single Nucleotide, Prolactin, Proto-Oncogene Proteins c-maf, Waist Circumference",
author = "{den Hoed}, M and J Luan and C Langenberg and C Cooper and Sayer, {A A} and K Jameson and M Kumari and M Kivimaki and Hingorani, {A D} and Anders Gr{\o}ntved and K-T Khaw and U Ekelund and Wareham, {N J} and Loos, {R J F}",
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month = "2",
doi = "10.1038/ijo.2012.34",
language = "English",
volume = "37",
pages = "191--6",
journal = "International Journal of Obesity",
issn = "0307-0565",
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den Hoed, M, Luan, J, Langenberg, C, Cooper, C, Sayer, AA, Jameson, K, Kumari, M, Kivimaki, M, Hingorani, AD, Grøntved, A, Khaw, K-T, Ekelund, U, Wareham, NJ & Loos, RJF 2013, 'Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples', International Journal of Obesity, bind 37, nr. 2, s. 191-6. https://doi.org/10.1038/ijo.2012.34

Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples. / den Hoed, M; Luan, J; Langenberg, C; Cooper, C; Sayer, A A; Jameson, K; Kumari, M; Kivimaki, M; Hingorani, A D; Grøntved, Anders; Khaw, K-T; Ekelund, U; Wareham, N J; Loos, R J F.

I: International Journal of Obesity, Bind 37, Nr. 2, 02.2013, s. 191-6.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples

AU - den Hoed, M

AU - Luan, J

AU - Langenberg, C

AU - Cooper, C

AU - Sayer, A A

AU - Jameson, K

AU - Kumari, M

AU - Kivimaki, M

AU - Hingorani, A D

AU - Grøntved, Anders

AU - Khaw, K-T

AU - Ekelund, U

AU - Wareham, N J

AU - Loos, R J F

PY - 2013/2

Y1 - 2013/2

N2 - 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 age(2) 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 (β=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.

AB - 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 age(2) 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 (β=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.

KW - Adolescent

KW - Adult

KW - Age of Onset

KW - Body Mass Index

KW - Carrier Proteins

KW - Case-Control Studies

KW - Child

KW - England

KW - European Continental Ancestry Group

KW - Female

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Male

KW - Membrane Glycoproteins

KW - Middle Aged

KW - Obesity, Morbid

KW - Odds Ratio

KW - Phenotype

KW - Polymorphism, Single Nucleotide

KW - Prolactin

KW - Proto-Oncogene Proteins c-maf

KW - Waist Circumference

U2 - 10.1038/ijo.2012.34

DO - 10.1038/ijo.2012.34

M3 - Journal article

C2 - 22430306

VL - 37

SP - 191

EP - 196

JO - International Journal of Obesity

JF - International Journal of Obesity

SN - 0307-0565

IS - 2

ER -