Genome-wide discovery of genetic loci that uncouple excess adiposity from its comorbidities

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Genome-wide discovery of genetic loci that uncouple excess adiposity from its comorbidities. / Huang, Lam O; Rauch, Alexander; Mazzaferro, Eugenia; Preuss, Michael; Carobbio, Stefania; Bayrak, Cigdem S; Chami, Nathalie; Wang, Zhe; Schick, Ursula M; Yang, Nancy; Itan, Yuval; Vidal-Puig, Antonio; den Hoed, Marcel; Mandrup, Susanne; Kilpeläinen, Tuomas O; Loos, Ruth J. F.

In: Nature Metabolism, Vol. 3, No. 2, 2021, p. 228-243.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Huang, LO, Rauch, A, Mazzaferro, E, Preuss, M, Carobbio, S, Bayrak, CS, Chami, N, Wang, Z, Schick, UM, Yang, N, Itan, Y, Vidal-Puig, A, den Hoed, M, Mandrup, S, Kilpeläinen, TO & Loos, RJF 2021, 'Genome-wide discovery of genetic loci that uncouple excess adiposity from its comorbidities', Nature Metabolism, vol. 3, no. 2, pp. 228-243. https://doi.org/10.1038/s42255-021-00346-2

APA

Huang, L. O., Rauch, A., Mazzaferro, E., Preuss, M., Carobbio, S., Bayrak, C. S., Chami, N., Wang, Z., Schick, U. M., Yang, N., Itan, Y., Vidal-Puig, A., den Hoed, M., Mandrup, S., Kilpeläinen, T. O., & Loos, R. J. F. (2021). Genome-wide discovery of genetic loci that uncouple excess adiposity from its comorbidities. Nature Metabolism, 3(2), 228-243. https://doi.org/10.1038/s42255-021-00346-2

Vancouver

Huang LO, Rauch A, Mazzaferro E, Preuss M, Carobbio S, Bayrak CS et al. Genome-wide discovery of genetic loci that uncouple excess adiposity from its comorbidities. Nature Metabolism. 2021;3(2):228-243. https://doi.org/10.1038/s42255-021-00346-2

Author

Huang, Lam O ; Rauch, Alexander ; Mazzaferro, Eugenia ; Preuss, Michael ; Carobbio, Stefania ; Bayrak, Cigdem S ; Chami, Nathalie ; Wang, Zhe ; Schick, Ursula M ; Yang, Nancy ; Itan, Yuval ; Vidal-Puig, Antonio ; den Hoed, Marcel ; Mandrup, Susanne ; Kilpeläinen, Tuomas O ; Loos, Ruth J. F. / Genome-wide discovery of genetic loci that uncouple excess adiposity from its comorbidities. In: Nature Metabolism. 2021 ; Vol. 3, No. 2. pp. 228-243.

Bibtex

@article{68c66a73b7264fccabede06138512e75,
title = "Genome-wide discovery of genetic loci that uncouple excess adiposity from its comorbidities",
abstract = "Obesity is a major risk factor for cardiometabolic diseases. Nevertheless, a substantial proportion of individuals with obesity do not suffer cardiometabolic comorbidities. The mechanisms that uncouple adiposity from its cardiometabolic complications are not fully understood. Here, we identify 62 loci of which the same allele is significantly associated with both higher adiposity and lower cardiometabolic risk. Functional analyses show that the 62 loci are enriched for genes expressed in adipose tissue, and for regulatory variants that influence nearby genes that affect adipocyte differentiation. Genes prioritized in each locus support a key role of fat distribution (FAM13A, IRS1 and PPARG) and adipocyte function (ALDH2, CCDC92, DNAH10, ESR1, FAM13A, MTOR, PIK3R1 and VEGFB). Several additional mechanisms are involved as well, such as insulin-glucose signalling (ADCY5, ARAP1, CREBBP, FAM13A, MTOR, PEPD, RAC1 and SH2B3), energy expenditure and fatty acid oxidation (IGF2BP2), browning of white adipose tissue (CSK, VEGFA, VEGFB and SLC22A3) and inflammation (SH2B3, DAGLB and ADCY9). Some of these genes may represent therapeutic targets to reduce cardiometabolic risk linked to excess adiposity.",
author = "Huang, {Lam O} and Alexander Rauch and Eugenia Mazzaferro and Michael Preuss and Stefania Carobbio and Bayrak, {Cigdem S} and Nathalie Chami and Zhe Wang and Schick, {Ursula M} and Nancy Yang and Yuval Itan and Antonio Vidal-Puig and {den Hoed}, Marcel and Susanne Mandrup and Kilpel{\"a}inen, {Tuomas O} and Loos, {Ruth J. F.}",
year = "2021",
doi = "10.1038/s42255-021-00346-2",
language = "English",
volume = "3",
pages = "228--243",
journal = "Nature Metabolism",
issn = "2522-5812",
publisher = "Springer",
number = "2",

}

RIS

TY - JOUR

T1 - Genome-wide discovery of genetic loci that uncouple excess adiposity from its comorbidities

AU - Huang, Lam O

AU - Rauch, Alexander

AU - Mazzaferro, Eugenia

AU - Preuss, Michael

AU - Carobbio, Stefania

AU - Bayrak, Cigdem S

AU - Chami, Nathalie

AU - Wang, Zhe

AU - Schick, Ursula M

AU - Yang, Nancy

AU - Itan, Yuval

AU - Vidal-Puig, Antonio

AU - den Hoed, Marcel

AU - Mandrup, Susanne

AU - Kilpeläinen, Tuomas O

AU - Loos, Ruth J. F.

PY - 2021

Y1 - 2021

N2 - Obesity is a major risk factor for cardiometabolic diseases. Nevertheless, a substantial proportion of individuals with obesity do not suffer cardiometabolic comorbidities. The mechanisms that uncouple adiposity from its cardiometabolic complications are not fully understood. Here, we identify 62 loci of which the same allele is significantly associated with both higher adiposity and lower cardiometabolic risk. Functional analyses show that the 62 loci are enriched for genes expressed in adipose tissue, and for regulatory variants that influence nearby genes that affect adipocyte differentiation. Genes prioritized in each locus support a key role of fat distribution (FAM13A, IRS1 and PPARG) and adipocyte function (ALDH2, CCDC92, DNAH10, ESR1, FAM13A, MTOR, PIK3R1 and VEGFB). Several additional mechanisms are involved as well, such as insulin-glucose signalling (ADCY5, ARAP1, CREBBP, FAM13A, MTOR, PEPD, RAC1 and SH2B3), energy expenditure and fatty acid oxidation (IGF2BP2), browning of white adipose tissue (CSK, VEGFA, VEGFB and SLC22A3) and inflammation (SH2B3, DAGLB and ADCY9). Some of these genes may represent therapeutic targets to reduce cardiometabolic risk linked to excess adiposity.

AB - Obesity is a major risk factor for cardiometabolic diseases. Nevertheless, a substantial proportion of individuals with obesity do not suffer cardiometabolic comorbidities. The mechanisms that uncouple adiposity from its cardiometabolic complications are not fully understood. Here, we identify 62 loci of which the same allele is significantly associated with both higher adiposity and lower cardiometabolic risk. Functional analyses show that the 62 loci are enriched for genes expressed in adipose tissue, and for regulatory variants that influence nearby genes that affect adipocyte differentiation. Genes prioritized in each locus support a key role of fat distribution (FAM13A, IRS1 and PPARG) and adipocyte function (ALDH2, CCDC92, DNAH10, ESR1, FAM13A, MTOR, PIK3R1 and VEGFB). Several additional mechanisms are involved as well, such as insulin-glucose signalling (ADCY5, ARAP1, CREBBP, FAM13A, MTOR, PEPD, RAC1 and SH2B3), energy expenditure and fatty acid oxidation (IGF2BP2), browning of white adipose tissue (CSK, VEGFA, VEGFB and SLC22A3) and inflammation (SH2B3, DAGLB and ADCY9). Some of these genes may represent therapeutic targets to reduce cardiometabolic risk linked to excess adiposity.

U2 - 10.1038/s42255-021-00346-2

DO - 10.1038/s42255-021-00346-2

M3 - Journal article

C2 - 33619380

VL - 3

SP - 228

EP - 243

JO - Nature Metabolism

JF - Nature Metabolism

SN - 2522-5812

IS - 2

ER -

ID: 257967843