Combined analyses of 20 common obesity susceptibility variants

Camilla Helene Sandholt; Thomas Sparsø; Niels Grarup; Anders Albrechtsen; Katrine Almind; Lars Hansen; Ulla Toft; Torben Jørgensen; Torben Hansen; Oluf Pedersen

doi:10.2337/db09-1042

Combined analyses of 20 common obesity susceptibility variants

Camilla Helene Sandholt, Thomas Sparsø, Niels Grarup, Anders Albrechtsen, Katrine Almind, Lars Hansen, Ulla Toft, Torben Jørgensen, Torben Hansen, Oluf Pedersen

44 Citations (Scopus)

Abstract

OBJECTIVE - Genome-wide association studies and linkage studies have identified 20 validated genetic variants associated with obesity and/or related phenotypes. The variants are common, and they individually exhibit small-to-modest effect sizes. RESEARCH DESIGN AND METHODS - In this study we investigate the combined effect of these variants and their ability to discriminate between normal weight and overweight/obese individuals. We applied receiver operating characteristics (ROC) curves, and estimated the area under the ROC curve (AUC) as a measure of the discriminatory ability. The analyses were performed cross-sectionally in the population-based Inter99 cohort where 1,725 normal weight, 1,519 overweight, and 681 obese individuals were successfully genotyped for all 20 variants. RESULTS - When combining all variants, the 10% of the study participants who carried more than 22 risk-alleles showed a significant increase in probability of being both overweight with an odds ratio of 2.00 (1.47-2.72), P = 4.0 × 10 ^-5, and obese with an OR of 2.62 (1.76-3.92), P = 6.4 × 10 ^-7, compared with the 10% of the study participants who carried less than 14 risk-alleles. Discrimination ability for overweight and obesity, using the 20 single nucleotide polymorphisms (SNPs), was determined to AUCs of 0.53 and 0.58, respectively. When combining SNP data with conventional nongenetic risk factors of obesity, the discrimination ability increased to 0.64 for overweight and 0.69 for obesity. The latter is significantly higher (P < 0.001) than for the nongenetic factors alone (AUC = 0.67). CONCLUSIONS - The discriminative value of the 20 validated common obesity variants is at present time sparse and too weak for clinical utility, however, they add to increase the discrimination ability of conventional nongenetic risk factors.

Original language	English
Journal	Diabetes
Volume	59
Issue number	7
Pages (from-to)	1667-73
Number of pages	7
ISSN	0012-1797
DOIs	https://doi.org/10.2337/db09-1042
Publication status	Published - Jul 2010

Keywords

Alleles
Body Mass Index
Female
Gene Frequency
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Male
Middle Aged
Obesity
Odds Ratio
Overweight
Polymorphism, Single Nucleotide
ROC Curve
Regression Analysis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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@article{9642b4b74ffe4b23912a25ef47d10064,

title = "Combined analyses of 20 common obesity susceptibility variants",

abstract = "OBJECTIVE - Genome-wide association studies and linkage studies have identified 20 validated genetic variants associated with obesity and/or related phenotypes. The variants are common, and they individually exhibit small-to-modest effect sizes. RESEARCH DESIGN AND METHODS - In this study we investigate the combined effect of these variants and their ability to discriminate between normal weight and overweight/obese individuals. We applied receiver operating characteristics (ROC) curves, and estimated the area under the ROC curve (AUC) as a measure of the discriminatory ability. The analyses were performed cross-sectionally in the population-based Inter99 cohort where 1,725 normal weight, 1,519 overweight, and 681 obese individuals were successfully genotyped for all 20 variants. RESULTS - When combining all variants, the 10% of the study participants who carried more than 22 risk-alleles showed a significant increase in probability of being both overweight with an odds ratio of 2.00 (1.47-2.72), P = 4.0 × 10 -5, and obese with an OR of 2.62 (1.76-3.92), P = 6.4 × 10 -7, compared with the 10% of the study participants who carried less than 14 risk-alleles. Discrimination ability for overweight and obesity, using the 20 single nucleotide polymorphisms (SNPs), was determined to AUCs of 0.53 and 0.58, respectively. When combining SNP data with conventional nongenetic risk factors of obesity, the discrimination ability increased to 0.64 for overweight and 0.69 for obesity. The latter is significantly higher (P < 0.001) than for the nongenetic factors alone (AUC = 0.67). CONCLUSIONS - The discriminative value of the 20 validated common obesity variants is at present time sparse and too weak for clinical utility, however, they add to increase the discrimination ability of conventional nongenetic risk factors.",

keywords = "Alleles, Body Mass Index, Female, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Obesity, Odds Ratio, Overweight, Polymorphism, Single Nucleotide, ROC Curve, Regression Analysis",

author = "Sandholt, {Camilla Helene} and Thomas Spars{\o} and Niels Grarup and Anders Albrechtsen and Katrine Almind and Lars Hansen and Ulla Toft and Torben J{\o}rgensen and Torben Hansen and Oluf Pedersen",

year = "2010",

month = jul,

doi = "10.2337/db09-1042",

language = "English",

volume = "59",

pages = "1667--73",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association",

number = "7",

}

TY - JOUR

T1 - Combined analyses of 20 common obesity susceptibility variants

AU - Sandholt, Camilla Helene

AU - Sparsø, Thomas

AU - Grarup, Niels

AU - Albrechtsen, Anders

AU - Almind, Katrine

AU - Hansen, Lars

AU - Toft, Ulla

AU - Jørgensen, Torben

AU - Hansen, Torben

AU - Pedersen, Oluf

PY - 2010/7

Y1 - 2010/7

N2 - OBJECTIVE - Genome-wide association studies and linkage studies have identified 20 validated genetic variants associated with obesity and/or related phenotypes. The variants are common, and they individually exhibit small-to-modest effect sizes. RESEARCH DESIGN AND METHODS - In this study we investigate the combined effect of these variants and their ability to discriminate between normal weight and overweight/obese individuals. We applied receiver operating characteristics (ROC) curves, and estimated the area under the ROC curve (AUC) as a measure of the discriminatory ability. The analyses were performed cross-sectionally in the population-based Inter99 cohort where 1,725 normal weight, 1,519 overweight, and 681 obese individuals were successfully genotyped for all 20 variants. RESULTS - When combining all variants, the 10% of the study participants who carried more than 22 risk-alleles showed a significant increase in probability of being both overweight with an odds ratio of 2.00 (1.47-2.72), P = 4.0 × 10 -5, and obese with an OR of 2.62 (1.76-3.92), P = 6.4 × 10 -7, compared with the 10% of the study participants who carried less than 14 risk-alleles. Discrimination ability for overweight and obesity, using the 20 single nucleotide polymorphisms (SNPs), was determined to AUCs of 0.53 and 0.58, respectively. When combining SNP data with conventional nongenetic risk factors of obesity, the discrimination ability increased to 0.64 for overweight and 0.69 for obesity. The latter is significantly higher (P < 0.001) than for the nongenetic factors alone (AUC = 0.67). CONCLUSIONS - The discriminative value of the 20 validated common obesity variants is at present time sparse and too weak for clinical utility, however, they add to increase the discrimination ability of conventional nongenetic risk factors.

AB - OBJECTIVE - Genome-wide association studies and linkage studies have identified 20 validated genetic variants associated with obesity and/or related phenotypes. The variants are common, and they individually exhibit small-to-modest effect sizes. RESEARCH DESIGN AND METHODS - In this study we investigate the combined effect of these variants and their ability to discriminate between normal weight and overweight/obese individuals. We applied receiver operating characteristics (ROC) curves, and estimated the area under the ROC curve (AUC) as a measure of the discriminatory ability. The analyses were performed cross-sectionally in the population-based Inter99 cohort where 1,725 normal weight, 1,519 overweight, and 681 obese individuals were successfully genotyped for all 20 variants. RESULTS - When combining all variants, the 10% of the study participants who carried more than 22 risk-alleles showed a significant increase in probability of being both overweight with an odds ratio of 2.00 (1.47-2.72), P = 4.0 × 10 -5, and obese with an OR of 2.62 (1.76-3.92), P = 6.4 × 10 -7, compared with the 10% of the study participants who carried less than 14 risk-alleles. Discrimination ability for overweight and obesity, using the 20 single nucleotide polymorphisms (SNPs), was determined to AUCs of 0.53 and 0.58, respectively. When combining SNP data with conventional nongenetic risk factors of obesity, the discrimination ability increased to 0.64 for overweight and 0.69 for obesity. The latter is significantly higher (P < 0.001) than for the nongenetic factors alone (AUC = 0.67). CONCLUSIONS - The discriminative value of the 20 validated common obesity variants is at present time sparse and too weak for clinical utility, however, they add to increase the discrimination ability of conventional nongenetic risk factors.

KW - Alleles

KW - Body Mass Index

KW - Female

KW - Gene Frequency

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Male

KW - Middle Aged

KW - Obesity

KW - Odds Ratio

KW - Overweight

KW - Polymorphism, Single Nucleotide

KW - ROC Curve

KW - Regression Analysis

U2 - 10.2337/db09-1042

DO - 10.2337/db09-1042

M3 - Journal article

C2 - 20110568

SN - 0012-1797

VL - 59

SP - 1667

EP - 1673

JO - Diabetes

JF - Diabetes

IS - 7

ER -

Combined analyses of 20 common obesity susceptibility variants

Abstract

Keywords

UN SDGs

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