Einzeltreffer — DigiBib

The problem of the genetics of related phenotypes is often addressed by analyzing adjusted-model traits, but such traits warrant cautious interpretation. Here, we adopt a joint view of adiposity traits in ~322,154 subjects (GIANT consortium). We classify 159 signals associated with body mass index (BMI), waist-to-hip ratio (WHR), or WHR adjusted for BMI (WHRadjBMI) at P < 5 × 10 -8 , into four classes based on the direction of their effects on BMI and WHR. Our classes help differentiate adiposity genetics with respect to anthropometry, fat depots, and metabolic health. Class-specific Mendelian randomization reveals that variants associated with both WHR-decrease and BMI increase are linked to metabolically rather favorable adiposity through beneficial hip fat. Class-specific enrichment analyses implicate digestive systems as a pathway in adiposity genetics. Our results demonstrate that WHRadjBMI variants capture relevant effects of "unexpected fat distribution given the BMI" and that a joint view of the genetics underlying related phenotypes can inform on important biology.

Titel:	A joint view on genetic variants for adiposity differentiates subtypes with distinct metabolic implications.
Autor/in / Beteiligte Person:	Winkler, TW ; Günther, F ; Höllerer, S ; Zimmermann, M ; Loos, RJ ; Kutalik, Z ; Heid, IM
Link:	Full Text Finder (Volltext)
Zeitschrift:	Nature communications, Jg. 9 (2018-05-16), Heft 1, S. 1946
Veröffentlichung:	[London] : Nature Pub. Group, 2018
Medientyp:	academicJournal
ISSN:	2041-1723 (electronic)
DOI:	10.1038/s41467-018-04124-9
Schlagwort:	Adipose Tissue metabolism Energy Metabolism genetics Genome-Wide Association Study methods Humans Meta-Analysis as Topic Obesity classification Obesity genetics Obesity metabolism Polymorphism, Single Nucleotide Adiposity genetics Body Mass Index Genetic Variation Waist-Hip Ratio
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Language: English [Nat Commun] 2018 May 16; Vol. 9 (1), pp. 1946. <i>Date of Electronic Publication: </i>2018 May 16. MeSH Terms: Body Mass Index* ; Genetic Variation* ; Waist-Hip Ratio* ; Adiposity / *genetics ; Adipose Tissue / metabolism ; Energy Metabolism / genetics ; Genome-Wide Association Study / methods ; Humans ; Meta-Analysis as Topic ; Obesity / classification ; Obesity / genetics ; Obesity / metabolism ; Polymorphism, Single Nucleotide References: JAMA. 2017 Feb 14;317(6):626-634. (PMID: 28196256) ; J Clin Endocrinol Metab. 2014 Oct;99(10):E1870-6. (PMID: 24937536) ; Nat Genet. 2017 Jan;49(1):125-130. (PMID: 27918534) ; Nat Genet. 2010 Feb;42(2):105-16. (PMID: 20081858) ; Nature. 2017 Oct 11;550(7675):204-213. (PMID: 29022597) ; Nat Genet. 2015 Oct;47(10):1121-1130. (PMID: 26343387) ; BMC Cardiovasc Disord. 2008 Mar 17;8:6. (PMID: 18366642) ; Nature. 2015 Feb 12;518(7538):197-206. (PMID: 25673413) ; Cell Metab. 2015 Feb 3;21(2):262-273. (PMID: 25651180) ; Genet Epidemiol. 2013 Nov;37(7):658-65. (PMID: 24114802) ; Nat Genet. 2018 Nov;50(11):1593-1599. (PMID: 30349118) ; Nat Genet. 2014 Nov;46(11):1173-86. (PMID: 25282103) ; Nature. 2015 Feb 12;518(7538):187-196. (PMID: 25673412) ; Nat Genet. 2012 Sep;44(9):981-90. (PMID: 22885922) ; Am J Hum Genet. 2015 Feb 5;96(2):329-39. (PMID: 25640676) ; JAMA Cardiol. 2017 Aug 1;2(8):882-889. (PMID: 28678979) ; Science. 2016 Oct 7;354(6308):69-73. (PMID: 27846494) ; Diabetes. 2006 Oct;55(10):2771-8. (PMID: 17003342) ; N Engl J Med. 2010 Dec 9;363(24):2339-50. (PMID: 21142536) ; Nat Genet. 2013 Nov;45(11):1274-1283. (PMID: 24097068) ; Diabetes Care. 2010 Jul;33(7):1635-9. (PMID: 20413524) ; PLoS Genet. 2013 Jun;9(6):e1003500. (PMID: 23754948) ; Nat Rev Genet. 2016 Apr;17(4):197-206. (PMID: 26972588) ; PLoS Genet. 2012;8(3):e1002607. (PMID: 22479202) ; Genetics. 2016 Oct;204(2):483-497. (PMID: 27527515) ; Am J Clin Nutr. 2002 Apr;75(4):683-8. (PMID: 11916754) ; Nat Genet. 2000 Sep;26(1):13. (PMID: 10973236) ; Nat Commun. 2017 Nov 28;8(1):1826. (PMID: 29184056) ; Nat Commun. 2015 Jan 19;6:5890. (PMID: 25597830) ; N Engl J Med. 2008 Nov 13;359(20):2105-20. (PMID: 19005195) ; Stat Med. 2016 May 20;35(11):1880-906. (PMID: 26661904) ; Nat Genet. 2017 Jan;49(1):17-26. (PMID: 27841877) ; Bioinformatics. 2015 Jan 15;31(2):259-61. (PMID: 25260699) ; Nature. 2015 Oct 1;526(7571):68-74. (PMID: 26432245) ; Hum Mol Genet. 2017 Mar 1;26(5):1018-1030. (PMID: 28040731) ; Diabetes. 2016 Aug;65(8):2448-60. (PMID: 27207519) ; Am J Hum Genet. 2007 Sep;81(3):559-75. (PMID: 17701901) ; Nat Rev Endocrinol. 2015 Feb;11(2):90-100. (PMID: 25365922) ; Nat Rev Endocrinol. 2016 Jul;12(7):375-6. (PMID: 27230950) ; Int J Obes (Lond). 2010 Jun;34(6):949-59. (PMID: 20065965) Grant Information: R01 DK075787 United States DK NIDDK NIH HHS; R01 DK107786 United States DK NIDDK NIH HHS; R01 DK110113 United States DK NIDDK NIH HHS; U01 HG007417 United States HG NHGRI NIH HHS Entry Date(s): Date Created: 20180518 Date Completed: 20181211 Latest Revision: 20240318 Update Code: 20240318 PubMed Central ID: PMC5956079

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A joint view on genetic variants for adiposity differentiates subtypes with distinct metabolic implications.