The causal relationship between human blood metabolites and the risk of visceral obesity: a mendelian randomization analysis
Abstract Background We aimed to explore the causal relationship between blood metabolites and the risk of visceral obesity, as measured by visceral adipose tissue (VAT). Methods Summary statistics for 486 blood metabolites and total, as well as sex-stratified, MRI-derived VAT measurements, adjusted...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Lipids in Health and Disease |
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| Online Access: | https://doi.org/10.1186/s12944-024-02035-x |
| _version_ | 1797273410948038656 |
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| author | Zhaoxiang Wang Qichao Yang |
| author_facet | Zhaoxiang Wang Qichao Yang |
| author_sort | Zhaoxiang Wang |
| collection | DOAJ |
| description | Abstract Background We aimed to explore the causal relationship between blood metabolites and the risk of visceral obesity, as measured by visceral adipose tissue (VAT). Methods Summary statistics for 486 blood metabolites and total, as well as sex-stratified, MRI-derived VAT measurements, adjusted for body mass index (BMI) and height, were collected from previous genome-wide association studies (GWAS). A two-sample Mendelian Randomization (MR) design was used. Comprehensive evaluation was further conducted, including sensitivity analysis, linkage disequilibrium score (LDSC) regression, Steiger test, and metabolic pathway analysis. Results After multiple testing correction, arachidonate (20:4n6) has been implicated in VAT accumulation (β = 0.35, 95%CI:0.18–0.52, P < 0.001; FDR = 0.025). Additionally, several blood metabolites were identified as potentially having causal relationship (FDR < 0.10). Among them, lysine (β = 0.67, 95%CI: 0.28–1.06, P < 0.001; FDR = 0.074), proline (β = 0.30, 95%CI:0.13–0.48, P < 0.001; FDR = 0.082), valerate (β = 0.50, 95%CI:0.23–0.78, P < 0.001, FDR = 0.091) are associated with an increased risk of VAT accumulation. On the other hand, glycine (β=-0.21, 95%CI: -0.33–0.09), P < 0.001, FDR = 0.076) have a protective effect against VAT accumulation. Most blood metabolites showed consistent trends between different sexes. Multivariable MR analysis demonstrated the effect of genetically predicted arachidonate (20:4n6) and proline on VAT remained after accounting for BMI and glycated hemoglobin (HbA1c). There is no evidence of heterogeneity, pleiotropy, and reverse causality. Conclusion Our MR findings suggest that these metabolites may serve as biomarkers, as well as for future mechanistic exploration and drug target selection of visceral obesity. |
| first_indexed | 2024-03-07T14:43:58Z |
| format | Article |
| id | doaj.art-b8fd6b2e13ad49cba202b68ec204ea40 |
| institution | Directory Open Access Journal |
| issn | 1476-511X |
| language | English |
| last_indexed | 2024-03-07T14:43:58Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Lipids in Health and Disease |
| spelling | doaj.art-b8fd6b2e13ad49cba202b68ec204ea402024-03-05T20:08:02ZengBMCLipids in Health and Disease1476-511X2024-02-0123111110.1186/s12944-024-02035-xThe causal relationship between human blood metabolites and the risk of visceral obesity: a mendelian randomization analysisZhaoxiang Wang0Qichao Yang1Department of Endocrinology, Affiliated Kunshan Hospital of Jiangsu UniversityDepartment of Endocrinology, Affiliated Wujin Hospital of Jiangsu UniversityAbstract Background We aimed to explore the causal relationship between blood metabolites and the risk of visceral obesity, as measured by visceral adipose tissue (VAT). Methods Summary statistics for 486 blood metabolites and total, as well as sex-stratified, MRI-derived VAT measurements, adjusted for body mass index (BMI) and height, were collected from previous genome-wide association studies (GWAS). A two-sample Mendelian Randomization (MR) design was used. Comprehensive evaluation was further conducted, including sensitivity analysis, linkage disequilibrium score (LDSC) regression, Steiger test, and metabolic pathway analysis. Results After multiple testing correction, arachidonate (20:4n6) has been implicated in VAT accumulation (β = 0.35, 95%CI:0.18–0.52, P < 0.001; FDR = 0.025). Additionally, several blood metabolites were identified as potentially having causal relationship (FDR < 0.10). Among them, lysine (β = 0.67, 95%CI: 0.28–1.06, P < 0.001; FDR = 0.074), proline (β = 0.30, 95%CI:0.13–0.48, P < 0.001; FDR = 0.082), valerate (β = 0.50, 95%CI:0.23–0.78, P < 0.001, FDR = 0.091) are associated with an increased risk of VAT accumulation. On the other hand, glycine (β=-0.21, 95%CI: -0.33–0.09), P < 0.001, FDR = 0.076) have a protective effect against VAT accumulation. Most blood metabolites showed consistent trends between different sexes. Multivariable MR analysis demonstrated the effect of genetically predicted arachidonate (20:4n6) and proline on VAT remained after accounting for BMI and glycated hemoglobin (HbA1c). There is no evidence of heterogeneity, pleiotropy, and reverse causality. Conclusion Our MR findings suggest that these metabolites may serve as biomarkers, as well as for future mechanistic exploration and drug target selection of visceral obesity.https://doi.org/10.1186/s12944-024-02035-xVisceral obesityBlood metabolitesGWASLDSCMendelian randomization analysis |
| spellingShingle | Zhaoxiang Wang Qichao Yang The causal relationship between human blood metabolites and the risk of visceral obesity: a mendelian randomization analysis Lipids in Health and Disease Visceral obesity Blood metabolites GWAS LDSC Mendelian randomization analysis |
| title | The causal relationship between human blood metabolites and the risk of visceral obesity: a mendelian randomization analysis |
| title_full | The causal relationship between human blood metabolites and the risk of visceral obesity: a mendelian randomization analysis |
| title_fullStr | The causal relationship between human blood metabolites and the risk of visceral obesity: a mendelian randomization analysis |
| title_full_unstemmed | The causal relationship between human blood metabolites and the risk of visceral obesity: a mendelian randomization analysis |
| title_short | The causal relationship between human blood metabolites and the risk of visceral obesity: a mendelian randomization analysis |
| title_sort | causal relationship between human blood metabolites and the risk of visceral obesity a mendelian randomization analysis |
| topic | Visceral obesity Blood metabolites GWAS LDSC Mendelian randomization analysis |
| url | https://doi.org/10.1186/s12944-024-02035-x |
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