Journal article
Conventional and genetic associations of adiposity with 1463 proteins in relatively lean Chinese adults
- Abstract:
- Adiposity is associated with multiple diseases and traits, but little is known about the causal relevance and mechanisms underlying these associations. Large-scale proteomic profiling, especially when integrated with genetic data, can clarify mechanisms linking adiposity with disease outcomes. We examined the associations of adiposity with plasma levels of 1463 proteins in 3977 Chinese adults, using measured and genetically-instrumented BMI. We further used two-sample bi-directional MR analyses to assess if certain proteins influenced adiposity, along with other (e.g. enrichment) analyses to clarify possible mechanisms underlying the observed associations. Overall, the mean (SD) baseline BMI was 23.9 (3.3) kg/m2, with only 6% being obese (i.e. BMI ≥ 30 kg/m2). Measured and genetically-instrumented BMI was significantly associated at FDR < 0.05 with levels of 1096 (positive/inverse: 826/270) and 307 (positive/inverse: 270/37) proteins, respectively, with FABP4, LEP, IL1RN, LSP1, GOLM2, TNFRSF6B, and ADAMTS15 showing the strongest positive and PON3, NCAN, LEPR, IGFBP2 and MOG showing the strongest inverse genetic associations. These associations were largely linear, in adiposity-to-protein direction, and replicated (> 90%) in Europeans of UKB (mean BMI 27.4 kg/m2). Enrichment analyses of the top > 50 BMI-associated proteins demonstrated their involvement in atherosclerosis, lipid metabolism, tumour progression and inflammation. Two-sample bi-directional MR analyses using cis-pQTLs identified in CKB GWAS found eight proteins (ITIH3, LRP11, SCAMP3, NUDT5, OGN, EFEMP1, TXNDC15, PRDX6) significantly affect levels of BMI, with NUDT5 also showing bi-directional association. The findings among relatively lean Chinese adults identified novel pathways by which adiposity may increase disease risks and novel potential targets for treatment of obesity and obesity-related diseases.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.5MB, Terms of use)
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- Publisher copy:
- 10.1007/s10654-023-01038-9
+ Wellcome Trust
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- Grant:
- 104085/Z/14/Z
- 212946/Z/18/Z
- 088158/Z/09/Z
- 202922/Z/16/Z
- Publisher:
- Springer
- Journal:
- European Journal of Epidemiology More from this journal
- Volume:
- 38
- Issue:
- 10
- Pages:
- 1089–1103
- Place of publication:
- Netherlands
- Publication date:
- 2023-09-07
- Acceptance date:
- 2023-07-28
- DOI:
- EISSN:
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1573-7284
- ISSN:
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0393-2990
- Pmid:
-
37676424
- Language:
-
English
- Keywords:
- Pubs id:
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1522649
- Local pid:
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pubs:1522649
- Deposit date:
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2024-03-05
Terms of use
- Copyright holder:
- Yao et al.
- Copyright date:
- 2023
- Rights statement:
- © The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Notes:
- This research was funded in whole, or in part, by the Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z). For the purpose of Open Access, the author has applied a CC-BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
- Licence:
- CC Attribution (CC BY)
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