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Background: Obesity and central obesity are multifactorial conditions with genetic and non-genetic (lifestyle and environmental) contributions. There is incomplete understanding of whether lifestyle modifies the translation from respective genetic risks into phenotypic obesity and central obesity, and to what extent genetic predisposition to obesity and central obesity is mediated via lifestyle factors.

Methods: This is a cross-sectional study of 201,466 (out of approximately 502,000) European participants from UK Biobank and tested for interactions and mediation role of lifestyle factors (diet quality; physical activity levels; total energy intake; sleep duration, and smoking and alcohol intake) between genetic risk for obesity and central obesity. BMI-PRS and WHR-PRS are exposures and obesity and central obesity are outcomes.

Results: Overall, 42.8% of the association between genetic predisposition to obesity and phenotypic obesity was explained by lifestyle: 0.9% by mediation and 41.9% by effect modification. A significant difference between men and women was found in central obesity; the figures were 42.1% (association explained by lifestyle), 1.4% (by mediation), and 40.7% (by modification) in women and 69.6% (association explained by lifestyle), 3.0% (by mediation), and 66.6% (by modification) in men.

Conclusions: A substantial proportion of the association between genetic predisposition to obesity/central obesity and phenotypic obesity/central obesity was explained by lifestyles. Future studies with repeated measures of obesity and lifestyle would be needed to clarify causation.

Titel:	How do lifestyle factors modify the association between genetic predisposition and obesity-related phenotypes? A 4-way decomposition analysis using UK Biobank.
Autor/in / Beteiligte Person:	Zhang, M ; Ward, J ; Strawbridge, RJ ; Celis-Morales, C ; Pell, JP ; Lyall, DM ; Ho, FK
Link:	Full Text Finder (Volltext)
Zeitschrift:	BMC medicine, Jg. 22 (2024-06-10), Heft 1, S. 230
Veröffentlichung:	[London] : BioMed Central, 2003-, 2024
Medientyp:	academicJournal
ISSN:	1741-7015 (electronic)
DOI:	10.1186/s12916-024-03436-6
Schlagwort:	Humans Male Female Cross-Sectional Studies United Kingdom epidemiology Middle Aged Aged Adult Obesity, Abdominal genetics Obesity, Abdominal epidemiology UK Biobank Genetic Predisposition to Disease Life Style Obesity genetics Obesity epidemiology Phenotype Biological Specimen Banks
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [BMC Med] 2024 Jun 10; Vol. 22 (1), pp. 230. <i>Date of Electronic Publication: </i>2024 Jun 10. MeSH Terms: Genetic Predisposition to Disease* ; Life Style* ; Obesity* / genetics ; Obesity* / epidemiology ; Phenotype* ; Biological Specimen Banks* ; Humans ; Male ; Female ; Cross-Sectional Studies ; United Kingdom / epidemiology ; Middle Aged ; Aged ; Adult ; Obesity, Abdominal / genetics ; Obesity, Abdominal / epidemiology ; UK Biobank References: Int J Obes (Lond). 2016 Mar;40(3):411-6. (PMID: 26392018) ; Am J Epidemiol. 2019 Oct 1;188(10):1858-1867. (PMID: 31318012) ; JAMA Cardiol. 2017 Aug 1;2(8):882-889. (PMID: 28678979) ; Nat Genet. 2010 Nov;42(11):937-48. (PMID: 20935630) ; Ann Intern Med. 2019 Nov 19;171(10):756-764. (PMID: 31569235) ; Hum Mol Genet. 2015 Aug 15;24(16):4728-38. (PMID: 25994509) ; Curr Opin Lipidol. 2014 Feb;25(1):27-34. (PMID: 24345984) ; Sci Rep. 2015 Oct 01;5:14726. (PMID: 26423639) ; Mol Psychiatry. 2015 Feb;20(1):133-39. (PMID: 24863145) ; J Clin Invest. 2021 Jan 4;131(1):. (PMID: 33393504) ; Pediatr Obes. 2014 Apr;9(2):e35-46. (PMID: 23529959) ; World Health Organ Tech Rep Ser. 2000;894:i-xii, 1-253. (PMID: 11234459) ; Mayo Clin Proc. 2021 Sep;96(9):2418-2431. (PMID: 34366141) ; PLoS Genet. 2017 Sep 5;13(9):e1006977. (PMID: 28873402) ; Crit Rev Food Sci Nutr. 2022;62(29):8078-8098. (PMID: 33998940) ; Nature. 2015 Feb 12;518(7538):187-196. (PMID: 25673412) ; Sleep Health. 2017 Oct;3(5):383-388. (PMID: 28923198) ; Int J Obes (Lond). 2017 Dec;41(12):1761-1768. (PMID: 28736445) ; Ann Epidemiol. 2015 Jun;25(6):406-413.e6. (PMID: 25749558) ; Int J Epidemiol. 2017 Apr 1;46(2):559-575. (PMID: 28073954) ; Med Sci Sports Exerc. 2003 Aug;35(8):1381-95. (PMID: 12900694) ; PLoS One. 2014 Mar 13;9(3):e91442. (PMID: 24626232) ; Nat Med. 2019 Nov;25(11):1644-1646. (PMID: 31700172) ; Curr Obes Rep. 2015 Mar;4(1):122-30. (PMID: 25741455) ; Br J Nutr. 2016 Feb 28;115(4):681-6. (PMID: 26652593) ; PLoS One. 2015 Apr 17;10(4):e0123579. (PMID: 25886648) ; Epidemiology. 2014 Sep;25(5):749-61. (PMID: 25000145) ; PLoS One. 2012;7(9):e45815. (PMID: 23029258) ; Hum Genomics. 2022 Jan 29;16(1):3. (PMID: 35093177) ; Nature. 2018 Oct;562(7726):203-209. (PMID: 30305743) ; Am J Epidemiol. 2017 Nov 1;186(9):1026-1034. (PMID: 28641372) ; Nat Rev Endocrinol. 2019 May;15(5):288-298. (PMID: 30814686) ; J Obes. 2017;2017:3245270. (PMID: 28607773) ; PLoS Med. 2011 Nov;8(11):e1001116. (PMID: 22069379) ; Obesity (Silver Spring). 2019 Apr;27(4):653-661. (PMID: 30900409) ; Am J Clin Nutr. 2017 Apr;105(4):980-990. (PMID: 28251931) ; Physiol Behav. 2015 Dec 1;152(Pt B):494-501. (PMID: 26166156) ; Int J Obes Relat Metab Disord. 1999 Nov;23(11):1192-201. (PMID: 10578210) ; Am J Hum Genet. 2015 Oct 1;97(4):576-92. (PMID: 26430803) ; Am J Epidemiol. 2023 Apr 6;192(4):514-516. (PMID: 35231933) ; PLoS Med. 2015 Mar 31;12(3):e1001779. (PMID: 25826379) ; Physiol Behav. 2005 Dec 15;86(5):633-9. (PMID: 16229869) ; Am J Clin Nutr. 2018 Dec 1;108(6):1291-1300. (PMID: 30351367) ; Crit Rev Food Sci Nutr. 2024;64(11):3235-3263. (PMID: 36222100) ; PLoS Med. 2010 Aug 31;7(8):. (PMID: 20824172) ; J Healthc Eng. 2018 Feb 1;2018:1564748. (PMID: 29599941) ; Lancet. 2012 Mar 31;379(9822):1173-4. (PMID: 22463865) ; Br J Nutr. 2007 Feb;97(2):219-31. (PMID: 17298689) ; Eur Heart J. 2007 Apr;28(7):850-6. (PMID: 17403720) ; Am J Clin Nutr. 2018 Sep 1;108(3):445-452. (PMID: 29982344) Contributed Indexing: Keywords: BMI-PRS; Central obesity; Obesity; Total lifestyle factors; WHR-PRS Entry Date(s): Date Created: 20240609 Date Completed: 20240609 Latest Revision: 20240612 Update Code: 20240612 PubMed Central ID: PMC11163778

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How do lifestyle factors modify the association between genetic predisposition and obesity-related phenotypes? A 4-way decomposition analysis using UK Biobank.