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Article: Shared genetic etiology and causality between body fat percentage and cardiovascular diseases: a large-scale genome-wide cross-trait analysis

TitleShared genetic etiology and causality between body fat percentage and cardiovascular diseases: a large-scale genome-wide cross-trait analysis
Authors
KeywordsBody fat percentage
Cardiovascular diseases
Shared genetics
Genetic correlation
Mendelian randomization
Issue Date2021
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmcmed/
Citation
BMC Medicine, 2021, v. 19 n. 1, p. article no. 100 How to Cite?
AbstractBackground: Accumulating evidences have suggested that high body fat percentage (BF%) often occurs in parallel with cardiovascular diseases (CVDs), implying a common etiology between them. However, the shared genetic etiology underlying BF% and CVDs remains unclear. Methods: Using large-scale genome-wide association study (GWAS) data, we investigated shared genetics between BF% (N = 100,716) and 10 CVD-related traits (n = 6968-977,323) with linkage disequilibrium score regression, multi-trait analysis of GWAS, and transcriptome-wide association analysis, and evaluated causal associations using Mendelian randomization. Results: We found strong positive genetic correlations between BF% and heart failure (HF) (Rg = 0.47, P = 1.27 × 10− 22) and coronary artery disease (CAD) (Rg = 0.22, P = 3.26 × 10− 07). We identified 5 loci and 32 gene-tissue pairs shared between BF% and HF, as well as 16 loci and 28 gene-tissue pairs shared between BF% and CAD. The loci were enriched in blood vessels and brain tissues, while the gene-tissue pairs were enriched in the nervous, cardiovascular, and exo-/endocrine system. In addition, we observed that BF% was causally related with a higher risk of HF (odds ratio 1.63 per 1-SD increase in BF%, P = 4.16 × 10–04) using a MR approach. Conclusions: Our findings suggest that BF% and CVDs have shared genetic etiology and targeted reduction of BF% may improve cardiovascular outcomes. This work advances our understanding of the genetic basis underlying co-morbid obesity and CVDs and opens up a new way for early prevention of CVDs.
Persistent Identifierhttp://hdl.handle.net/10722/305893
ISSN
2023 Impact Factor: 7.0
2023 SCImago Journal Rankings: 2.711
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhuang, Z-
dc.contributor.authorYao, M-
dc.contributor.authorWong, JYY-
dc.contributor.authorLiu, Z-
dc.contributor.authorHuang, T-
dc.date.accessioned2021-10-20T10:15:50Z-
dc.date.available2021-10-20T10:15:50Z-
dc.date.issued2021-
dc.identifier.citationBMC Medicine, 2021, v. 19 n. 1, p. article no. 100-
dc.identifier.issn1741-7015-
dc.identifier.urihttp://hdl.handle.net/10722/305893-
dc.description.abstractBackground: Accumulating evidences have suggested that high body fat percentage (BF%) often occurs in parallel with cardiovascular diseases (CVDs), implying a common etiology between them. However, the shared genetic etiology underlying BF% and CVDs remains unclear. Methods: Using large-scale genome-wide association study (GWAS) data, we investigated shared genetics between BF% (N = 100,716) and 10 CVD-related traits (n = 6968-977,323) with linkage disequilibrium score regression, multi-trait analysis of GWAS, and transcriptome-wide association analysis, and evaluated causal associations using Mendelian randomization. Results: We found strong positive genetic correlations between BF% and heart failure (HF) (Rg = 0.47, P = 1.27 × 10− 22) and coronary artery disease (CAD) (Rg = 0.22, P = 3.26 × 10− 07). We identified 5 loci and 32 gene-tissue pairs shared between BF% and HF, as well as 16 loci and 28 gene-tissue pairs shared between BF% and CAD. The loci were enriched in blood vessels and brain tissues, while the gene-tissue pairs were enriched in the nervous, cardiovascular, and exo-/endocrine system. In addition, we observed that BF% was causally related with a higher risk of HF (odds ratio 1.63 per 1-SD increase in BF%, P = 4.16 × 10–04) using a MR approach. Conclusions: Our findings suggest that BF% and CVDs have shared genetic etiology and targeted reduction of BF% may improve cardiovascular outcomes. This work advances our understanding of the genetic basis underlying co-morbid obesity and CVDs and opens up a new way for early prevention of CVDs.-
dc.languageeng-
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmcmed/-
dc.relation.ispartofBMC Medicine-
dc.rightsBMC Medicine. Copyright © BioMed Central Ltd.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectBody fat percentage-
dc.subjectCardiovascular diseases-
dc.subjectShared genetics-
dc.subjectGenetic correlation-
dc.subjectMendelian randomization-
dc.titleShared genetic etiology and causality between body fat percentage and cardiovascular diseases: a large-scale genome-wide cross-trait analysis-
dc.typeArticle-
dc.identifier.emailLiu, Z: zhhliu@hku.hk-
dc.identifier.authorityLiu, Z=rp02429-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/s12916-021-01972-z-
dc.identifier.pmid33910581-
dc.identifier.pmcidPMC8082910-
dc.identifier.scopuseid_2-s2.0-85104939441-
dc.identifier.hkuros327203-
dc.identifier.volume19-
dc.identifier.issue1-
dc.identifier.spagearticle no. 100-
dc.identifier.epagearticle no. 100-
dc.identifier.isiWOS:000647037600001-
dc.publisher.placeUnited Kingdom-

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