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Obesity (Silver Spring). 2017 Jul;25(7):1277-1283. doi: 10.1002/oby.21874. Epub 2017 May 25.

Genetic determination of body fat distribution and the attributive influence on metabolism.

Fehlert E1,2,3, Wagner R1,2,3, Ketterer C1,2,3, Böhm A1,2,3, Machann J2,3,4, Fritsche L1,2,3, Machicao F1,2,3, Schick F2,3,4, Staiger H2,3,5,6, Stefan N1,2,3, Häring HU1,2,3,6, Fritsche A1,2,3, Heni M1,2,3.

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Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University, Tübingen, Germany.
Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.
German Center for Diabetes Research (DZD), Tübingen, Germany.
Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, Eberhard Karls University, Tübingen, Germany.
Institute of Pharmaceutical Sciences, Department of Pharmacy and Biochemistry, Eberhard Karls University Tübingen, Tübingen, Germany.
Interfaculty Center for Pharmacogenomics and Pharma Research at the Eberhard Karls University Tübingen, Tübingen, Germany.



Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) associated with estimates of body fat distribution. Using predefined risk allele scores, the correlation of these scores with precisely quantified body fat distribution assessed by magnetic resonance (MR) imaging techniques and with metabolic traits was investigated.


Data from 4,944 MR scans from 915 subjects of European ancestry were analyzed. Body fat distribution was determined by MR imaging and liver fat content by 1 H-MR spectroscopy. All subjects underwent a five-point 75-g oral glucose tolerance test. A total of 65 SNPs with reported genome-wide significant associations regarding estimates of body fat distribution were genotyped. Four genetic risk scores were created by summation of risk alleles.


A higher allelic load of waist-to-hip ratio SNPs was associated with lower insulin sensitivity, higher postchallenge glucose levels, and more visceral and less subcutaneous fat mass.


GWAS-derived polymorphisms estimating body fat distribution are associated with distinct patterns of body fat distribution exactly measured by MR. Only the risk score associated with the waist-to-hip ratio in GWAS showed an unhealthy pattern of metabolism and body fat distribution. This score might be useful for predicting diseases associated with genetically determined, unhealthy obesity.

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