Common variants in LEPR, IL6, AMD1, and NAMPT do not associate with risk of juvenile and childhood obesity in Danes: a case-control study

Mette Hollensted; Tarun Veer Singh Ahluwalia; Christian Theil Have; Niels Grarup; Cilius Esmann Fonvig; Tenna Ruest Haarmark Nielsen; Cæcilie Trier; Lavinia Paternoster; Oluf Pedersen; Jens-Christian Holm; Thorkild I A Sørensen; Torben Hansen

doi:10.1186/s12881-015-0253-3

Common variants in LEPR, IL6, AMD1, and NAMPT do not associate with risk of juvenile and childhood obesity in Danes: a case-control study

Mette Hollensted, Tarun Veer Singh Ahluwalia, Christian Theil Have, Niels Grarup, Cilius Esmann Fonvig, Tenna Ruest Haarmark Nielsen, Cæcilie Trier, Lavinia Paternoster, Oluf Pedersen, Jens-Christian Holm, Thorkild I A Sørensen, Torben Hansen

7 Citations (Scopus)

Abstract

BACKGROUND: Childhood obesity is a highly heritable disorder, for which the underlying genetic architecture is largely unknown. Four common variants involved in inflammatory-adipokine triggering (IL6 rs2069845, LEPR rs1137100, NAMPT rs3801266, and AMD1 rs2796749) have recently been associated with obesity and related traits in Indian children. The current study aimed to examine the effect of these variants on risk of childhood/juvenile onset obesity and on obesity-related quantitative traits in two Danish cohorts.

METHODS: Genotype information was obtained for 1461 young Caucasian men from the Genetics of Overweight Young Adults (GOYA) study (overweight/obese: 739 and normal weight: 722) and the Danish Childhood Obesity Biobank (TDCOB; overweight/obese: 1022 and normal weight: 650). Overweight/obesity was defined as having a body mass index (BMI) ≥25 kg/m(2); among children and youths, this cut-off was defined using age and sex-specific cut-offs corresponding to an adult body mass index ≥25 kg/m(2). Risk of obesity was assessed using a logistic regression model whereas obesity-related quantitative measures were analyzed using a general linear model (based on z-scores) stratifying on the case status and adjusting for age and gender. Meta-analyses were performed using the fixed effects model.

RESULTS: No statistically significant association with childhood/juvenile obesity was found for any of the four gene variants among the individual or combined analyses (rs2069845 OR: 0.94 CI: 0.85-1.04; rs1137100 OR: 1.01 CI: 0.90-1.14; rs3801266: 0.96 CI: 0.84-1.10; rs2796749 OR: 1.02 CI: 0.90-1.15; p > 0.05). However, among normal weight children and juvenile men, the LEPR rs1137100 A-allele significantly associated with lower BMI (β = -0.12, p = 0.0026).

CONCLUSIONS: The IL6, LEPR, NAMPT, and AMD1 gene variants previously found to associate among Indian children did not associate with risk of obesity or obesity-related quantitative measures among Caucasian children and juvenile men from Denmark.

Original language	English
Article number	105
Journal	BMC Medical Genetics
Volume	16
Number of pages	9
ISSN	1471-2350
DOIs	https://doi.org/10.1186/s12881-015-0253-3
Publication status	Published - 11 Nov 2015

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10.1186/s12881-015-0253-3Licence: CC BY

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Hollensted, M., Ahluwalia, T. V. S., Have, C. T., Grarup, N., Fonvig, C. E., Nielsen, T. R. H., Trier, C., Paternoster, L., Pedersen, O., Holm, J-C., Sørensen, T. I. A., & Hansen, T. (2015). Common variants in LEPR, IL6, AMD1, and NAMPT do not associate with risk of juvenile and childhood obesity in Danes: a case-control study. BMC Medical Genetics, 16, [105]. https://doi.org/10.1186/s12881-015-0253-3

Hollensted, M, Ahluwalia, TVS, Have, CT, Grarup, N, Fonvig, CE, Nielsen, TRH, Trier, C, Paternoster, L, Pedersen, O , Holm, J-C , Sørensen, TIA & Hansen, T 2015, 'Common variants in LEPR, IL6, AMD1, and NAMPT do not associate with risk of juvenile and childhood obesity in Danes: a case-control study', BMC Medical Genetics, vol. 16, 105. https://doi.org/10.1186/s12881-015-0253-3

@article{ffded9308b1c4c3a9e38b3517afc68d4,

title = "Common variants in LEPR, IL6, AMD1, and NAMPT do not associate with risk of juvenile and childhood obesity in Danes: a case-control study",

abstract = "BACKGROUND: Childhood obesity is a highly heritable disorder, for which the underlying genetic architecture is largely unknown. Four common variants involved in inflammatory-adipokine triggering (IL6 rs2069845, LEPR rs1137100, NAMPT rs3801266, and AMD1 rs2796749) have recently been associated with obesity and related traits in Indian children. The current study aimed to examine the effect of these variants on risk of childhood/juvenile onset obesity and on obesity-related quantitative traits in two Danish cohorts.METHODS: Genotype information was obtained for 1461 young Caucasian men from the Genetics of Overweight Young Adults (GOYA) study (overweight/obese: 739 and normal weight: 722) and the Danish Childhood Obesity Biobank (TDCOB; overweight/obese: 1022 and normal weight: 650). Overweight/obesity was defined as having a body mass index (BMI) ≥25 kg/m(2); among children and youths, this cut-off was defined using age and sex-specific cut-offs corresponding to an adult body mass index ≥25 kg/m(2). Risk of obesity was assessed using a logistic regression model whereas obesity-related quantitative measures were analyzed using a general linear model (based on z-scores) stratifying on the case status and adjusting for age and gender. Meta-analyses were performed using the fixed effects model.RESULTS: No statistically significant association with childhood/juvenile obesity was found for any of the four gene variants among the individual or combined analyses (rs2069845 OR: 0.94 CI: 0.85-1.04; rs1137100 OR: 1.01 CI: 0.90-1.14; rs3801266: 0.96 CI: 0.84-1.10; rs2796749 OR: 1.02 CI: 0.90-1.15; p > 0.05). However, among normal weight children and juvenile men, the LEPR rs1137100 A-allele significantly associated with lower BMI (β = -0.12, p = 0.0026).CONCLUSIONS: The IL6, LEPR, NAMPT, and AMD1 gene variants previously found to associate among Indian children did not associate with risk of obesity or obesity-related quantitative measures among Caucasian children and juvenile men from Denmark.",

author = "Mette Hollensted and Ahluwalia, {Tarun Veer Singh} and Have, {Christian Theil} and Niels Grarup and Fonvig, {Cilius Esmann} and Nielsen, {Tenna Ruest Haarmark} and C{\ae}cilie Trier and Lavinia Paternoster and Oluf Pedersen and Jens-Christian Holm and S{\o}rensen, {Thorkild I A} and Torben Hansen",

year = "2015",

month = nov,

day = "11",

doi = "10.1186/s12881-015-0253-3",

language = "English",

volume = "16",

journal = "B M C Medical Genetics",

issn = "1471-2350",

publisher = "BioMed Central Ltd.",

}

TY - JOUR

T1 - Common variants in LEPR, IL6, AMD1, and NAMPT do not associate with risk of juvenile and childhood obesity in Danes

T2 - a case-control study

AU - Hollensted, Mette

AU - Ahluwalia, Tarun Veer Singh

AU - Have, Christian Theil

AU - Grarup, Niels

AU - Fonvig, Cilius Esmann

AU - Nielsen, Tenna Ruest Haarmark

AU - Trier, Cæcilie

AU - Paternoster, Lavinia

AU - Pedersen, Oluf

AU - Holm, Jens-Christian

AU - Sørensen, Thorkild I A

AU - Hansen, Torben

PY - 2015/11/11

Y1 - 2015/11/11

N2 - BACKGROUND: Childhood obesity is a highly heritable disorder, for which the underlying genetic architecture is largely unknown. Four common variants involved in inflammatory-adipokine triggering (IL6 rs2069845, LEPR rs1137100, NAMPT rs3801266, and AMD1 rs2796749) have recently been associated with obesity and related traits in Indian children. The current study aimed to examine the effect of these variants on risk of childhood/juvenile onset obesity and on obesity-related quantitative traits in two Danish cohorts.METHODS: Genotype information was obtained for 1461 young Caucasian men from the Genetics of Overweight Young Adults (GOYA) study (overweight/obese: 739 and normal weight: 722) and the Danish Childhood Obesity Biobank (TDCOB; overweight/obese: 1022 and normal weight: 650). Overweight/obesity was defined as having a body mass index (BMI) ≥25 kg/m(2); among children and youths, this cut-off was defined using age and sex-specific cut-offs corresponding to an adult body mass index ≥25 kg/m(2). Risk of obesity was assessed using a logistic regression model whereas obesity-related quantitative measures were analyzed using a general linear model (based on z-scores) stratifying on the case status and adjusting for age and gender. Meta-analyses were performed using the fixed effects model.RESULTS: No statistically significant association with childhood/juvenile obesity was found for any of the four gene variants among the individual or combined analyses (rs2069845 OR: 0.94 CI: 0.85-1.04; rs1137100 OR: 1.01 CI: 0.90-1.14; rs3801266: 0.96 CI: 0.84-1.10; rs2796749 OR: 1.02 CI: 0.90-1.15; p > 0.05). However, among normal weight children and juvenile men, the LEPR rs1137100 A-allele significantly associated with lower BMI (β = -0.12, p = 0.0026).CONCLUSIONS: The IL6, LEPR, NAMPT, and AMD1 gene variants previously found to associate among Indian children did not associate with risk of obesity or obesity-related quantitative measures among Caucasian children and juvenile men from Denmark.

AB - BACKGROUND: Childhood obesity is a highly heritable disorder, for which the underlying genetic architecture is largely unknown. Four common variants involved in inflammatory-adipokine triggering (IL6 rs2069845, LEPR rs1137100, NAMPT rs3801266, and AMD1 rs2796749) have recently been associated with obesity and related traits in Indian children. The current study aimed to examine the effect of these variants on risk of childhood/juvenile onset obesity and on obesity-related quantitative traits in two Danish cohorts.METHODS: Genotype information was obtained for 1461 young Caucasian men from the Genetics of Overweight Young Adults (GOYA) study (overweight/obese: 739 and normal weight: 722) and the Danish Childhood Obesity Biobank (TDCOB; overweight/obese: 1022 and normal weight: 650). Overweight/obesity was defined as having a body mass index (BMI) ≥25 kg/m(2); among children and youths, this cut-off was defined using age and sex-specific cut-offs corresponding to an adult body mass index ≥25 kg/m(2). Risk of obesity was assessed using a logistic regression model whereas obesity-related quantitative measures were analyzed using a general linear model (based on z-scores) stratifying on the case status and adjusting for age and gender. Meta-analyses were performed using the fixed effects model.RESULTS: No statistically significant association with childhood/juvenile obesity was found for any of the four gene variants among the individual or combined analyses (rs2069845 OR: 0.94 CI: 0.85-1.04; rs1137100 OR: 1.01 CI: 0.90-1.14; rs3801266: 0.96 CI: 0.84-1.10; rs2796749 OR: 1.02 CI: 0.90-1.15; p > 0.05). However, among normal weight children and juvenile men, the LEPR rs1137100 A-allele significantly associated with lower BMI (β = -0.12, p = 0.0026).CONCLUSIONS: The IL6, LEPR, NAMPT, and AMD1 gene variants previously found to associate among Indian children did not associate with risk of obesity or obesity-related quantitative measures among Caucasian children and juvenile men from Denmark.

U2 - 10.1186/s12881-015-0253-3

DO - 10.1186/s12881-015-0253-3

M3 - Journal article

C2 - 26558825

SN - 1471-2350

VL - 16

JO - B M C Medical Genetics

JF - B M C Medical Genetics

M1 - 105

ER -

Common variants in LEPR, IL6, AMD1, and NAMPT do not associate with risk of juvenile and childhood obesity in Danes: a case-control study

Abstract

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