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Title:
Conventional and genetic associations of adiposity with 1463 proteins in relatively lean Chinese adults | European Journal of Epidemiology
Description:
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.
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Keywords {🔍}
proteins, bmi, analyses, associations, genetic, pubmed, article, adiposity, google, scholar, protein, study, participants, ckb, levels, significantly, obesity, cas, china, central, data, multiple, causal, ukb, plasma, chinese, diseases, enrichment, positive, inverse, pathways, observational, fig, bidirectional, gwas, disease, showing, identified, analysis, kgm, itih, body, including, main, research, adults, chen, biobank, traits, cispqtls,
Topics {✒️}
interviewer-administered laptop-based questionnaire showing bi-directional association adult body-mass index sample bi-directional mr sex-combined trans-ancestry gwas bi-directional mr analyses bi-directional mr methods genome-wide association studies nonlinear exposure-outcome relationship bi-directional causal relationship ecm-receptor interaction pathways open access users article download pdf creatine kinase u-type stringent bonferroni-corrected thresholds passed bonferroni-corrected threshold mendelian randomisation estimates fatty acid-binding protein sample mendelian randomization cytokine-mediated signaling pathways pre-determined correction factor body-mass index body mass index joint multiple-snp analysis east asian populations trans-ethnic bmi-gs bi-directional mr tissue-specific expression analyses gs-free bmi strata gs-free bmi startum china kadoorie biobank nested case-cohort study sex-related biological mechanisms genome-wide genotyping data org/site/data+access develop formal collaboration de block ce lean chinese adults multiple adiposity-related traits national key research robert clarke open access larger sample size cell–cell adhesion including protein–protein interactions ecm-receptor interaction multi-testing adjusted threshold junshi chen zhengming chen large-scale proteomic profiling
Questions {❓}
- The role of Ras-associated protein 1 (Rap1) in cancer: bad actor or good player?
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WebPage:
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headline:Conventional and genetic associations of adiposity with 1463 proteins in relatively lean Chinese adults
description: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.
datePublished:2023-09-07T00:00:00Z
dateModified:2023-09-07T00:00:00Z
pageStart:1089
pageEnd:1103
license:http://creativecommons.org/licenses/by/4.0/
sameAs:https://doi.org/10.1007/s10654-023-01038-9
keywords:
Obesity
Body mass index
Proteomics
Mendelian randomization analysis
Drug discovery
East Asians
Epidemiology
Public Health
Infectious Diseases
Cardiology
Oncology
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headline:Conventional and genetic associations of adiposity with 1463 proteins in relatively lean Chinese adults
description: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.
datePublished:2023-09-07T00:00:00Z
dateModified:2023-09-07T00:00:00Z
pageStart:1089
pageEnd:1103
license:http://creativecommons.org/licenses/by/4.0/
sameAs:https://doi.org/10.1007/s10654-023-01038-9
keywords:
Obesity
Body mass index
Proteomics
Mendelian randomization analysis
Drug discovery
East Asians
Epidemiology
Public Health
Infectious Diseases
Cardiology
Oncology
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