Genome-Wide and Abdominal MRI-Imaging Data Provides Evidence that a Genetically Determined Favourable Adiposity Phenotype is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease and Hypertension

Yingjie Ji; Andrianos M. Yiorkas; Francesca Frau; Dennis Mook-kanamori; Harald Staiger; E. Louise Thomas; Naeimeh Atabaki-pasdar; Archie Campbell; Jessica Tyrrell; Samuel E. Jones; Robin N. Beaumont; Andrew R. Wood; Marcus A. Tuke; Katherine S. Ruth; Anubha Mahajan; Anna Murray; Rachel M. Freathy; Michael N. Weedon; Andrew T. Hattersley; Caroline Hayward; Jürgen Machann; Hans-ulrich Häring; Paul Franks; Renée De Mutsert; Ewan Pearson; Norbert Stefan; Timothy M. Frayling; Karla V. Allebrandt; Jimmy D. Bell; Alexandra I. Blakemore; Hanieh Yaghootkar

doi:10.2337/db18-0708

Genome-Wide and Abdominal MRI-Imaging Data Provides Evidence that a Genetically Determined Favourable Adiposity Phenotype is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease and Hypertension

Yingjie Ji, Andrianos M. Yiorkas, Francesca Frau, Dennis Mook-kanamori, Harald Staiger, E. Louise Thomas, Naeimeh Atabaki-pasdar, Archie Campbell, Jessica Tyrrell, Samuel E. Jones, Robin N. Beaumont, Andrew R. Wood, Marcus A. Tuke, Katherine S. Ruth, Anubha Mahajan, Anna Murray, Rachel M. Freathy, Michael N. Weedon, Andrew T. Hattersley, Caroline HaywardJürgen Machann, Hans-ulrich Häring, Paul Franks, Renée De Mutsert, Ewan Pearson, Norbert Stefan, Timothy M. Frayling, Karla V. Allebrandt, Jimmy D. Bell, Alexandra I. Blakemore, Hanieh Yaghootkar

Research output: Contribution to journal › Article › peer-review

Abstract

Recent genetic studies have identified alleles associated with opposite effects on adiposity and risk of type 2 diabetes. We aimed to identify more of these variants and test the hypothesis that such “favourable adiposity” alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined magnetic resonance imaging (MRI) data with genome-wide association studies (GWAS) of body fat % and metabolic traits. We report 14 alleles, including 7 newly characterized alleles, associated with higher adiposity, but a favourable metabolic profile. Consistent with previous studies, individuals carrying more “favourable adiposity” alleles had higher body fat % and higher BMI, but lower risk of type 2 diabetes, heart disease and hypertension. These individuals also had higher subcutaneous fat, but lower liver fat and lower visceral-to-subcutaneous adipose tissue ratio. Individual alleles associated with higher body fat % but lower liver fat and lower risk of type 2 diabetes included those in PPARG, GRB14 and IRS1, whilst the allele in ANKRD55 was paradoxically associated with higher visceral fat but lower risk of type 2 diabetes. Most identified “favourable adiposity” alleles are associated with higher subcutaneous and lower liver fat, a mechanism consistent with the beneficial effects of storing excess triglyceride in metabolically low risk depots.

Original language	English
Pages (from-to)	db180708
Number of pages	96
Journal	Diabetes
Early online date	23 Oct 2018
DOIs	https://doi.org/10.2337/db18-0708
Publication status	E-pub ahead of print - 23 Oct 2018

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Stratifying Resilience and Depression Longitudinally
McIntosh, A. (Principal Investigator), Deary, I. (Co-investigator), Evans, K. (Co-investigator), Haley, C. (Co-investigator) & Porteous, D. (Co-investigator)
UK-based charities
1/01/15 → 30/06/21
Project: Research
Generation Scotland
Porteous, D. (Principal Investigator)
UK central government bodies/local authorities, health and hospital authorities
1/04/11 → 31/03/14
Project: Research
Genetic Health 21st Century
Porteous, D. (Principal Investigator), Laurie, G. (Co-investigator) & Tait, J. (Co-investigator)
UK central government bodies/local authorities, health and hospital authorities
1/10/03 → 31/08/07
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Ji, Y., Yiorkas, A. M., Frau, F., Mook-kanamori, D., Staiger, H., Thomas, E. L., Atabaki-pasdar, N., Campbell, A., Tyrrell, J., Jones, S. E., Beaumont, R. N., Wood, A. R., Tuke, M. A., Ruth, K. S., Mahajan, A., Murray, A., Freathy, R. M., Weedon, M. N., Hattersley, A. T., ... Yaghootkar, H. (2018). Genome-Wide and Abdominal MRI-Imaging Data Provides Evidence that a Genetically Determined Favourable Adiposity Phenotype is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease and Hypertension. Diabetes , db180708. Advance online publication. https://doi.org/10.2337/db18-0708

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title = "Genome-Wide and Abdominal MRI-Imaging Data Provides Evidence that a Genetically Determined Favourable Adiposity Phenotype is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease and Hypertension",

abstract = "Recent genetic studies have identified alleles associated with opposite effects on adiposity and risk of type 2 diabetes. We aimed to identify more of these variants and test the hypothesis that such “favourable adiposity” alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined magnetic resonance imaging (MRI) data with genome-wide association studies (GWAS) of body fat % and metabolic traits. We report 14 alleles, including 7 newly characterized alleles, associated with higher adiposity, but a favourable metabolic profile. Consistent with previous studies, individuals carrying more “favourable adiposity” alleles had higher body fat % and higher BMI, but lower risk of type 2 diabetes, heart disease and hypertension. These individuals also had higher subcutaneous fat, but lower liver fat and lower visceral-to-subcutaneous adipose tissue ratio. Individual alleles associated with higher body fat % but lower liver fat and lower risk of type 2 diabetes included those in PPARG, GRB14 and IRS1, whilst the allele in ANKRD55 was paradoxically associated with higher visceral fat but lower risk of type 2 diabetes. Most identified “favourable adiposity” alleles are associated with higher subcutaneous and lower liver fat, a mechanism consistent with the beneficial effects of storing excess triglyceride in metabolically low risk depots.",

author = "Yingjie Ji and Yiorkas, {Andrianos M.} and Francesca Frau and Dennis Mook-kanamori and Harald Staiger and Thomas, {E. Louise} and Naeimeh Atabaki-pasdar and Archie Campbell and Jessica Tyrrell and Jones, {Samuel E.} and Beaumont, {Robin N.} and Wood, {Andrew R.} and Tuke, {Marcus A.} and Ruth, {Katherine S.} and Anubha Mahajan and Anna Murray and Freathy, {Rachel M.} and Weedon, {Michael N.} and Hattersley, {Andrew T.} and Caroline Hayward and J{\"u}rgen Machann and Hans-ulrich H{\"a}ring and Paul Franks and {De Mutsert}, Ren{\'e}e and Ewan Pearson and Norbert Stefan and Frayling, {Timothy M.} and Allebrandt, {Karla V.} and Bell, {Jimmy D.} and Blakemore, {Alexandra I.} and Hanieh Yaghootkar",

year = "2018",

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day = "23",

doi = "10.2337/db18-0708",

language = "English",

pages = "db180708",

journal = "Diabetes ",

issn = "0012-1797",

publisher = "American Diabetes Association Inc.",

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Ji, Y, Yiorkas, AM, Frau, F, Mook-kanamori, D, Staiger, H, Thomas, EL, Atabaki-pasdar, N, Campbell, A, Tyrrell, J, Jones, SE, Beaumont, RN, Wood, AR, Tuke, MA, Ruth, KS, Mahajan, A, Murray, A, Freathy, RM, Weedon, MN, Hattersley, AT, Hayward, C, Machann, J, Häring, H, Franks, P, De Mutsert, R, Pearson, E, Stefan, N, Frayling, TM, Allebrandt, KV, Bell, JD, Blakemore, AI & Yaghootkar, H 2018, 'Genome-Wide and Abdominal MRI-Imaging Data Provides Evidence that a Genetically Determined Favourable Adiposity Phenotype is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease and Hypertension', Diabetes , pp. db180708. https://doi.org/10.2337/db18-0708

Genome-Wide and Abdominal MRI-Imaging Data Provides Evidence that a Genetically Determined Favourable Adiposity Phenotype is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease and Hypertension. / Ji, Yingjie; Yiorkas, Andrianos M.; Frau, Francesca et al.
In: Diabetes , 23.10.2018, p. db180708.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Genome-Wide and Abdominal MRI-Imaging Data Provides Evidence that a Genetically Determined Favourable Adiposity Phenotype is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease and Hypertension

AU - Ji, Yingjie

AU - Yiorkas, Andrianos M.

AU - Frau, Francesca

AU - Mook-kanamori, Dennis

AU - Staiger, Harald

AU - Thomas, E. Louise

AU - Atabaki-pasdar, Naeimeh

AU - Campbell, Archie

AU - Tyrrell, Jessica

AU - Jones, Samuel E.

AU - Beaumont, Robin N.

AU - Wood, Andrew R.

AU - Tuke, Marcus A.

AU - Ruth, Katherine S.

AU - Mahajan, Anubha

AU - Murray, Anna

AU - Freathy, Rachel M.

AU - Weedon, Michael N.

AU - Hattersley, Andrew T.

AU - Hayward, Caroline

AU - Machann, Jürgen

AU - Häring, Hans-ulrich

AU - Franks, Paul

AU - De Mutsert, Renée

AU - Pearson, Ewan

AU - Stefan, Norbert

AU - Frayling, Timothy M.

AU - Allebrandt, Karla V.

AU - Bell, Jimmy D.

AU - Blakemore, Alexandra I.

AU - Yaghootkar, Hanieh

PY - 2018/10/23

Y1 - 2018/10/23

N2 - Recent genetic studies have identified alleles associated with opposite effects on adiposity and risk of type 2 diabetes. We aimed to identify more of these variants and test the hypothesis that such “favourable adiposity” alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined magnetic resonance imaging (MRI) data with genome-wide association studies (GWAS) of body fat % and metabolic traits. We report 14 alleles, including 7 newly characterized alleles, associated with higher adiposity, but a favourable metabolic profile. Consistent with previous studies, individuals carrying more “favourable adiposity” alleles had higher body fat % and higher BMI, but lower risk of type 2 diabetes, heart disease and hypertension. These individuals also had higher subcutaneous fat, but lower liver fat and lower visceral-to-subcutaneous adipose tissue ratio. Individual alleles associated with higher body fat % but lower liver fat and lower risk of type 2 diabetes included those in PPARG, GRB14 and IRS1, whilst the allele in ANKRD55 was paradoxically associated with higher visceral fat but lower risk of type 2 diabetes. Most identified “favourable adiposity” alleles are associated with higher subcutaneous and lower liver fat, a mechanism consistent with the beneficial effects of storing excess triglyceride in metabolically low risk depots.

AB - Recent genetic studies have identified alleles associated with opposite effects on adiposity and risk of type 2 diabetes. We aimed to identify more of these variants and test the hypothesis that such “favourable adiposity” alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined magnetic resonance imaging (MRI) data with genome-wide association studies (GWAS) of body fat % and metabolic traits. We report 14 alleles, including 7 newly characterized alleles, associated with higher adiposity, but a favourable metabolic profile. Consistent with previous studies, individuals carrying more “favourable adiposity” alleles had higher body fat % and higher BMI, but lower risk of type 2 diabetes, heart disease and hypertension. These individuals also had higher subcutaneous fat, but lower liver fat and lower visceral-to-subcutaneous adipose tissue ratio. Individual alleles associated with higher body fat % but lower liver fat and lower risk of type 2 diabetes included those in PPARG, GRB14 and IRS1, whilst the allele in ANKRD55 was paradoxically associated with higher visceral fat but lower risk of type 2 diabetes. Most identified “favourable adiposity” alleles are associated with higher subcutaneous and lower liver fat, a mechanism consistent with the beneficial effects of storing excess triglyceride in metabolically low risk depots.

U2 - 10.2337/db18-0708

DO - 10.2337/db18-0708

M3 - Article

SN - 0012-1797

SP - db180708

JO - Diabetes

JF - Diabetes

ER -

Ji Y, Yiorkas AM, Frau F, Mook-kanamori D, Staiger H, Thomas EL et al. Genome-Wide and Abdominal MRI-Imaging Data Provides Evidence that a Genetically Determined Favourable Adiposity Phenotype is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease and Hypertension. Diabetes . 2018 Oct 23;db180708. Epub 2018 Oct 23. doi: 10.2337/db18-0708

Genome-Wide and Abdominal MRI-Imaging Data Provides Evidence that a Genetically Determined Favourable Adiposity Phenotype is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease and Hypertension

Abstract

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Stratifying Resilience and Depression Longitudinally

Generation Scotland

Genetic Health 21st Century

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