Canine genome-wide association study identifies DENND1B as an obesity gene in dogs and humans

被引：0

作者：

Wallis, Natalie J. ^{[1
]}

Mcclellan, Alyce ^{[1
]}

Morseburg, Alexander ^{[2
,3
]}

Kentistou, Katherine A. ^{[4
]}

Jamaluddin, Aqfan ^{[5
,6
,7
]}

Dowsett, Georgina K. C. ^{[2
]}

Schofield, Ellen ^{[1
,8
]}

Morros-Nuevo, Anna ^{[1
]}

Saeed, Sadia ^{[9
,10
,11
]}

Lam, Brian Y. H. ^{[2
,3
]}

Sumanasekera, Natasha T. ^{[1
]}

Chan, Justine ^{[1
]}

Kumar, Sambhavi S. ^{[1
]}

Zhang, Rey M. ^{[1
]}

Wainwright, Jodie F. ^{[1
]}

Dittmann, Marie ^{[1
]}

Lakatos, Gabriella ^{[2
]}

Rainbow, Kara ^{[2
]}

Withers, David ^{[2
]}

Bounds, Rebecca ^{[2
,12
]}

Ma, Marcella ^{[2
,3
]}

German, Alexander J. ^{[13
,14
]}

Ladlow, Jane ^{[8
]}

Sargan, David ^{[8
]}

Froguel, Philippe ^{[9
,10
,11
]}

Farooqi, I. Sadaf ^{[2
,12
]}

Ong, Ken K. ^{[4
]}

Yeo, Giles S. H. ^{[2
,3
]}

Tadross, John A. ^{[2
,15
,16
]}

Perry, John R. B. ^{[2
,4
]}

Gorvin, Caroline M. ^{[5
,6
,7
]}

Raffan, Eleanor ^{[1
,2
]}

机构：

[1] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge, England

[2] Univ Cambridge, Inst Metab Sci, Metab Res Labs, Cambridge, England

[3] Univ Cambridge, Inst Metab Sci, MRC Metab Dis Unit, Cambridge, England

[4] Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England

[5] Univ Birmingham, Inst Metab & Syst Res, Birmingham, England

[6] Univ Birmingham, Ctr Membrane Prot & Receptors COMPARE, Birmingham, England

[7] Univ Nottingham, Ctr Membrane Prot & Receptors COMPARE, Nottingham, England

[8] Univ Cambridge, Dept Vet Med, Cambridge, England

[9] Inst Pasteur, CNRS, European Genom Inst Diabet, INSERM,UMR 1283,UMR 8199, Lille, France

[10] Univ Lille, Lille Univ Hosp, Lille, France

[11] Imperial Coll London, Dept Metab Digest & Reprod, London, England

[12] Natl Inst Hlth & Care Res NIHR Cambridge Biomed Re, Cambridge, England

[13] Univ Liverpool, Inst Life Course & Med Sci, Neston, England

[14] Univ Liverpool, Sch Vet Sci, Neston, England

[15] Cambridge Univ Hosp NHS Fdn Trust, Dept Histopathol, Cambridge, England

[16] Cambridge Univ Hosp NHS Fdn Trust, Cambridge Genom Lab, Cambridge, England

来源：

SCIENCE | 2025年 / 387卷 / 6741期

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会; 英国惠康基金;

关键词：

MELANOCYTE-STIMULATING HORMONE; SEVERE CHILDHOOD OBESITY; MIXED-MODEL ANALYSIS; BODY CONDITION; VARIANTS; TISSUE; HERITABILITY; POPULATION; RESOURCE; WEIGHT;

D O I：

10.1126/science.ads2145

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Obesity is a heritable disease, but its genetic basis is incompletely understood. Canine population history facilitates trait mapping. We performed a canine genome-wide association study for body condition score-a measure of obesity-in 241 Labrador retrievers. Using a cross-species approach, we showed that canine obesity genes are also associated with rare and common forms of obesity in humans. The lead canine association was within the gene DENN domain containing 1B (DENND1B). Each copy of the alternate allele was associated with similar to 7% greater body fat. We demonstrate a role for this gene in regulating signaling and trafficking of melanocortin 4 receptor, a critical controller of energy homeostasis. Thus, canine genetics identified obesity genes and mechanisms relevant to both dogs and humans.

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页数：11

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