Examining the Causal Inference of Leptin and Soluble Plasma Leptin Receptor Levels on Schizophrenia: A Mendelian Randomization Study
Background: Observational studies that have supported the role of the leptin level in schizophrenia (SCZ) risk are conflicting. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to investigate whether the circulating leptin and soluble plasma leptin receptor (sOB-R) levels p...
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2021.753224/full |
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| author | Guoqing Chen Qiuling Wang Ranran Xue Xia Liu Hao Yu |
| author_facet | Guoqing Chen Qiuling Wang Ranran Xue Xia Liu Hao Yu |
| author_sort | Guoqing Chen |
| collection | DOAJ |
| description | Background: Observational studies that have supported the role of the leptin level in schizophrenia (SCZ) risk are conflicting. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to investigate whether the circulating leptin and soluble plasma leptin receptor (sOB-R) levels play a causal role in SCZ risk.Methods: We first selected five independent single-nucleotide polymorphisms (SNPs) associated with the circulating leptin level and three independent SNPs associated with the sOB-R level from two genome-wide association studies (GWASs) of European individuals. Then, we extracted their associations with SCZ using a large-scale GWAS that consisted of 40,675 patients with SCZ and 64,643 controls of European ancestry. We performed an MR analysis using the inverse variance-weighted (IVW) method to examine the causal effect of leptin on SCZ risk. Moreover, we performed sensitivity analyses to verify our MR results using the weighted median and MR-Egger methods.Results: According to the IVW method, genetically predicted circulating leptin levels were not associated with SCZ risk (OR = 1.98, for per 1-SD unit increase in leptin level; 95% CI, 0.87–4.53; p = 0.10). In addition, the sOB-R level showed no causal effect on the SCZ risk using IVW (OR = 0.98 for per 1-SD unit increase in sOB-R level; 95% CI, 0.97–1.00; p = 0.06). Our sensitivity analysis results confirmed our MR findings.Conclusions: By estimating the causal effect of leptin on SCZ risk using the MR methods, we identified no effect of genetically predicted circulating leptin or the sOB-R level on SCZ. As such, our study suggests that leptin might not be a risk factor for SCZ. |
| first_indexed | 2024-12-19T18:24:37Z |
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| language | English |
| last_indexed | 2024-12-19T18:24:37Z |
| publishDate | 2021-10-01 |
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| series | Frontiers in Psychiatry |
| spelling | doaj.art-c4825cc2260349568652871afd0f5e1e2022-12-21T20:10:53ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402021-10-011210.3389/fpsyt.2021.753224753224Examining the Causal Inference of Leptin and Soluble Plasma Leptin Receptor Levels on Schizophrenia: A Mendelian Randomization StudyGuoqing Chen0Qiuling Wang1Ranran Xue2Xia Liu3Hao Yu4Department of Psychiatry, Jining Medical University, Jining, ChinaDepartment of Psychiatry, Shandong Daizhuang Hospital, Jining, ChinaDepartment of Psychiatry, Shandong Daizhuang Hospital, Jining, ChinaDepartment of Psychiatry, Shandong Daizhuang Hospital, Jining, ChinaDepartment of Psychiatry, Jining Medical University, Jining, ChinaBackground: Observational studies that have supported the role of the leptin level in schizophrenia (SCZ) risk are conflicting. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to investigate whether the circulating leptin and soluble plasma leptin receptor (sOB-R) levels play a causal role in SCZ risk.Methods: We first selected five independent single-nucleotide polymorphisms (SNPs) associated with the circulating leptin level and three independent SNPs associated with the sOB-R level from two genome-wide association studies (GWASs) of European individuals. Then, we extracted their associations with SCZ using a large-scale GWAS that consisted of 40,675 patients with SCZ and 64,643 controls of European ancestry. We performed an MR analysis using the inverse variance-weighted (IVW) method to examine the causal effect of leptin on SCZ risk. Moreover, we performed sensitivity analyses to verify our MR results using the weighted median and MR-Egger methods.Results: According to the IVW method, genetically predicted circulating leptin levels were not associated with SCZ risk (OR = 1.98, for per 1-SD unit increase in leptin level; 95% CI, 0.87–4.53; p = 0.10). In addition, the sOB-R level showed no causal effect on the SCZ risk using IVW (OR = 0.98 for per 1-SD unit increase in sOB-R level; 95% CI, 0.97–1.00; p = 0.06). Our sensitivity analysis results confirmed our MR findings.Conclusions: By estimating the causal effect of leptin on SCZ risk using the MR methods, we identified no effect of genetically predicted circulating leptin or the sOB-R level on SCZ. As such, our study suggests that leptin might not be a risk factor for SCZ.https://www.frontiersin.org/articles/10.3389/fpsyt.2021.753224/fullschizophrenialeptinsoluble plasma leptin receptorgenome-wide association study (GWAS)Mendelian randomization |
| spellingShingle | Guoqing Chen Qiuling Wang Ranran Xue Xia Liu Hao Yu Examining the Causal Inference of Leptin and Soluble Plasma Leptin Receptor Levels on Schizophrenia: A Mendelian Randomization Study Frontiers in Psychiatry schizophrenia leptin soluble plasma leptin receptor genome-wide association study (GWAS) Mendelian randomization |
| title | Examining the Causal Inference of Leptin and Soluble Plasma Leptin Receptor Levels on Schizophrenia: A Mendelian Randomization Study |
| title_full | Examining the Causal Inference of Leptin and Soluble Plasma Leptin Receptor Levels on Schizophrenia: A Mendelian Randomization Study |
| title_fullStr | Examining the Causal Inference of Leptin and Soluble Plasma Leptin Receptor Levels on Schizophrenia: A Mendelian Randomization Study |
| title_full_unstemmed | Examining the Causal Inference of Leptin and Soluble Plasma Leptin Receptor Levels on Schizophrenia: A Mendelian Randomization Study |
| title_short | Examining the Causal Inference of Leptin and Soluble Plasma Leptin Receptor Levels on Schizophrenia: A Mendelian Randomization Study |
| title_sort | examining the causal inference of leptin and soluble plasma leptin receptor levels on schizophrenia a mendelian randomization study |
| topic | schizophrenia leptin soluble plasma leptin receptor genome-wide association study (GWAS) Mendelian randomization |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2021.753224/full |
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