Conventional and genetic associations of adiposity with 1463 proteins in relatively lean Chinese adults
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 ex...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal article |
| Language: | English |
| Published: |
Springer
2023
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| _version_ | 1826312495010152448 |
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| author | Yao, P Iona, A Kartsonaki, C Said, S Wright, N Lin, K Pozarickij, A Millwood, I Fry, H Mazidi, M Chen, Y Du, H Bennett, D Avery, D Schmidt, D Pei, P Lv, J Yu, C Hill, M Chen, J Peto, R Walters, R Collins, R Li, L Clarke, R Chen, Z |
| author2 | China Kadoorie Biobank Collaborative Group |
| author_facet | China Kadoorie Biobank Collaborative Group Yao, P Iona, A Kartsonaki, C Said, S Wright, N Lin, K Pozarickij, A Millwood, I Fry, H Mazidi, M Chen, Y Du, H Bennett, D Avery, D Schmidt, D Pei, P Lv, J Yu, C Hill, M Chen, J Peto, R Walters, R Collins, R Li, L Clarke, R Chen, Z |
| author_sort | Yao, P |
| collection | OXFORD |
| 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/m<sup>2</sup>, with only 6% being obese (i.e. BMI ≥ 30 kg/m<sup>2</sup>). 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/m<sup>2</sup>). 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 <i>cis</i>-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. |
| first_indexed | 2024-03-07T08:29:49Z |
| format | Journal article |
| id | oxford-uuid:d99fb335-7461-43d1-a90b-d5e05cc7337d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:29:49Z |
| publishDate | 2023 |
| publisher | Springer |
| record_format | dspace |
| spelling | oxford-uuid:d99fb335-7461-43d1-a90b-d5e05cc7337d2024-03-05T15:05:45ZConventional and genetic associations of adiposity with 1463 proteins in relatively lean Chinese adultsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d99fb335-7461-43d1-a90b-d5e05cc7337dEnglishSymplectic ElementsSpringer2023Yao, PIona, AKartsonaki, CSaid, SWright, NLin, KPozarickij, AMillwood, IFry, HMazidi, MChen, YDu, HBennett, DAvery, DSchmidt, DPei, PLv, JYu, CHill, MChen, JPeto, RWalters, RCollins, RLi, LClarke, RChen, ZChina Kadoorie Biobank Collaborative GroupAdiposity 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/m<sup>2</sup>, with only 6% being obese (i.e. BMI ≥ 30 kg/m<sup>2</sup>). 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/m<sup>2</sup>). 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 <i>cis</i>-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. |
| spellingShingle | Yao, P Iona, A Kartsonaki, C Said, S Wright, N Lin, K Pozarickij, A Millwood, I Fry, H Mazidi, M Chen, Y Du, H Bennett, D Avery, D Schmidt, D Pei, P Lv, J Yu, C Hill, M Chen, J Peto, R Walters, R Collins, R Li, L Clarke, R Chen, Z Conventional and genetic associations of adiposity with 1463 proteins in relatively lean Chinese adults |
| title | Conventional and genetic associations of adiposity with 1463 proteins in relatively lean Chinese adults |
| title_full | Conventional and genetic associations of adiposity with 1463 proteins in relatively lean Chinese adults |
| title_fullStr | Conventional and genetic associations of adiposity with 1463 proteins in relatively lean Chinese adults |
| title_full_unstemmed | Conventional and genetic associations of adiposity with 1463 proteins in relatively lean Chinese adults |
| title_short | Conventional and genetic associations of adiposity with 1463 proteins in relatively lean Chinese adults |
| title_sort | conventional and genetic associations of adiposity with 1463 proteins in relatively lean chinese adults |
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