Large scale phenotype imputation and in vivo functional validation implicate ADAMTS14 as an adiposity gene.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 01 2023
19 01 2023
Historique:
received:
17
12
2020
accepted:
09
12
2022
entrez:
19
1
2023
pubmed:
20
1
2023
medline:
24
1
2023
Statut:
epublish
Résumé
Obesity remains an unmet global health burden. Detrimental anatomical distribution of body fat is a major driver of obesity-mediated mortality risk and is demonstrably heritable. However, our understanding of the full genetic contribution to human adiposity is incomplete, as few studies measure adiposity directly. To address this, we impute whole-body imaging adiposity phenotypes in UK Biobank from the 4,366 directly measured participants onto the rest of the cohort, greatly increasing our discovery power. Using these imputed phenotypes in 392,535 participants yielded hundreds of genome-wide significant associations, six of which replicate in independent cohorts. The leading causal gene candidate, ADAMTS14, is further investigated in a mouse knockout model. Concordant with the human association data, the Adamts14
Identifiants
pubmed: 36658113
doi: 10.1038/s41467-022-35563-0
pii: 10.1038/s41467-022-35563-0
pmc: PMC9852585
doi:
Substances chimiques
ADAMTS Proteins
EC 3.4.24.-
ADAMTS14 protein, human
EC 3.4.24.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
307Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Chief Scientist Office
ID : CZB/4/710
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R026408/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00007/10
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
Références
Int J Obes Relat Metab Disord. 1994 Jul;18(7):503-12
pubmed: 7920877
Appl Physiol Nutr Metab. 2008 Oct;33(5):997-1006
pubmed: 18923576
Am J Hum Genet. 2008 Sep;83(3):359-72
pubmed: 18760389
Matrix Biol. 2018 Sep;70:140-157
pubmed: 29649548
FASEB J. 2016 May;30(5):1741-56
pubmed: 26740262
Sci Rep. 2017 Dec 4;7(1):16878
pubmed: 29203879
Int J Obes (Lond). 2018 Apr;42(4):850-857
pubmed: 29151596
Sci Rep. 2016 Aug 11;6:31566
pubmed: 27511834
PLoS One. 2013 Jul 16;8(7):e68604
pubmed: 23874685
Nature. 2007 Jun 7;447(7145):661-78
pubmed: 17554300
PLoS One. 2019 May 30;14(5):e0217644
pubmed: 31145760
Nat Genet. 2016 May;48(5):481-7
pubmed: 27019110
Brief Bioinform. 2015 Jan;16(1):39-44
pubmed: 24008273
J Biol Chem. 2002 Feb 22;277(8):5756-66
pubmed: 11741898
PLoS Genet. 2012;8(5):e1002695
pubmed: 22589738
Hum Mol Genet. 2017 Sep 1;26(17):3432-3441
pubmed: 28854703
Sci Rep. 2020 Jun 26;10(1):10486
pubmed: 32591598
Science. 2007 May 11;316(5826):889-94
pubmed: 17434869
Br J Cancer. 1999 Jul;80 Suppl 1:95-103
pubmed: 10466767
Hum Mol Genet. 2018 Oct 15;27(20):3641-3649
pubmed: 30124842
Tohoku J Exp Med. 2008 Feb;214(2):105-12
pubmed: 18285667
Front Endocrinol (Lausanne). 2012 Feb 28;3:29
pubmed: 22645519
Mol Cell Biol. 2003 Jan;23(1):55-61
pubmed: 12482960
Prev Med. 2018 Jan;106:86-93
pubmed: 29030265
Gigascience. 2018 Aug 1;7(8):
pubmed: 30165448
Nat Genet. 2017 Jan;49(1):125-130
pubmed: 27918534
Mol Metab. 2014 Dec 04;4(2):93-105
pubmed: 25685697
JCI Insight. 2022 Apr 22;7(8):
pubmed: 35316211
PLoS Genet. 2014 May 15;10(5):e1004383
pubmed: 24830394
N Engl J Med. 2017 Jul 6;377(1):13-27
pubmed: 28604169
EMBO J. 2000 Apr 17;19(8):1745-54
pubmed: 10775259
Int J Obes (Lond). 2010 Nov;34(11):1618-24
pubmed: 20548304
Nat Genet. 2013 Jun;45(6):580-5
pubmed: 23715323
Nature. 2016 Sep 22;537(7621):508-514
pubmed: 27626380
Obesity (Silver Spring). 2016 Nov;24(11):2414-2421
pubmed: 27667735
Clin Nutr. 1993 Aug;12(4):236-42
pubmed: 16843318
Nucleic Acids Res. 2019 Jan 8;47(D1):D1005-D1012
pubmed: 30445434
Bioinformatics. 2016 Oct 15;32(20):3207-3209
pubmed: 27318201
Am J Pathol. 2002 May;160(5):1895-903
pubmed: 12000741
Nature. 2018 Oct;562(7726):203-209
pubmed: 30305743
Am J Clin Nutr. 2010 Aug;92(2):347-52
pubmed: 20519560
Nat Genet. 2017 Jan;49(1):17-26
pubmed: 27841877
Nat Commun. 2019 Jan 21;10(1):339
pubmed: 30664634
Cell. 2006 May 5;125(3):577-91
pubmed: 16678100
Hum Mol Genet. 2015 Jun 15;24(12):3305-13
pubmed: 25743184
Nat Rev Endocrinol. 2015 Feb;11(2):90-100
pubmed: 25365922
Br J Radiol. 2012 Jan;85(1009):1-10
pubmed: 21937614
Stem Cell Res Ther. 2020 Jan 29;11(1):41
pubmed: 31996252
PLoS Med. 2015 Mar 31;12(3):e1001779
pubmed: 25826379
J Clin Endocrinol Metab. 2010 Dec;95(12):5419-26
pubmed: 20843952
Science. 2015 May 8;348(6235):648-60
pubmed: 25954001
Nat Genet. 2018 Apr;50(4):621-629
pubmed: 29632380
World Health Organ Tech Rep Ser. 2000;894:i-xii, 1-253
pubmed: 11234459
Hum Mol Genet. 2019 Jan 1;28(1):166-174
pubmed: 30239722
Nature. 2015 Feb 12;518(7538):197-206
pubmed: 25673413
Arterioscler Thromb Vasc Biol. 2002 Mar 1;22(3):374-9
pubmed: 11884277
JAMA. 2018 Dec 25;320(24):2553-2563
pubmed: 30575882