Dataset Information

Causal Associations of Circulating Lipids with Osteoarthritis: A Bidirectional Mendelian Randomization Study.

ABSTRACT: Osteoarthritis (OA) imposes an increasing social burden due to global activity limitations, especially among the aged. Links between circulating lipids and OA have been reported; however, confounding data from observational studies have hindered causal conclusions. We used Mendelian randomization (MR) approach to evaluate the genetic causal effects of circulating apolipoproteins and lipoprotein lipids on OA risk. Genetic instruments at the genome-wide significance level (p < 5 × 10^-8) were selected from genome-wide association studies (n = 393,193-441,016 individuals). Summary-level OA data were obtained from the UK Biobank (39,427 cases, 378,169 controls). Bidirectional two-sample Mendelian randomization (MR) analyses used MR-Egger, weighted median, and MR-PRESSO for sensitivity analysis. Genetic predisposition to 1-SD increments of Apolipoprotein B (APOB), and low-density lipoprotein (LDL) was associated with a decreased risk of knee or hip OA (KHOA) (odds ratio (OR) = 0.925, 95% confidence interval (95% CI): 0.881-0.972, p = 0.002; OR = 0.898, 95% CI: 0.843-0.957, p = 0.001) and hip OA (HOA) (OR = 0.894; 95% CI: 0.832-0.961, p = 0.002; OR = 0.870 95% CI: 0.797-0.949, p = 0.002). Genetically predicted APOB showed an association with knee OA (KOA) (OR per SD increase, 0.930, 95% CI: 0.876-0.987, p = 0.016). The OR of KOA was 0.899 (95% CI: 0.835-0.968, p = 0.005) for a 1-SD increase in LDL. Apolipoprotein A1, high-density lipoprotein, and triglycerides showed no association. Inverse MR showed no causal effect of KOA, HOA, or KHOA on these serum lipids. Distinct protective genetic-influence patterns were observed for APOB and LDL on OA, offering new insights into relationships between lipids and OA risk and a better understanding of OA etiology.

SUBMITTER: Meng H

PROVIDER: S-EPMC9000847 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Causal Associations of Circulating Lipids with Osteoarthritis: A Bidirectional Mendelian Randomization Study.

Meng Hongen H Jiang Li L Song Zijun Z Wang Fudi F

Nutrients 20220322 7

Osteoarthritis (OA) imposes an increasing social burden due to global activity limitations, especially among the aged. Links between circulating lipids and OA have been reported; however, confounding data from observational studies have hindered causal conclusions. We used Mendelian randomization (MR) approach to evaluate the genetic causal effects of circulating apolipoproteins and lipoprotein lipids on OA risk. Genetic instruments at the genome-wide significance level (p < 5 × 10−8) were selec ...[more]

PMID: 35405941

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Project description:BackgroundPrevious epidemiological studies have reported associations between vitamin D and postpartum depression (PPD); however, the findings are inconsistent. This study employs bidirectional Mendelian Randomization (MR) to investigate the causal link between serum 25-hydroxyvitamin D [25(OH)D] levels and PPD. By utilizing genetic data from cohorts, this research aims to provide a more robust understanding of the potential relationship between vitamin D and PPD, addressing a critical gap in the current literature.MethodsA bidirectional MR analysis was conducted to investigate the genetic association between serum 25(OH)D and PPD using summary statistics extracted from GWAS datasets. The study included data from 15,668 patients with PPD and 376,755 healthy controls of European ancestry. The GWAS data for 25(OH)D were obtained from two studies within the UK Biobank, encompassing 496,946 and 79,366 participants. The primary analysis employed the inverse-variance weighted (IVW) method, while supplementary MR estimates were derived through the MR-Egger and weighted median (WME) methods. Furthermore, sensitivity analyses were implemented to ensure robustness and reliability, including Cochran's Q test, MR-PRESSO, MR-Egger intercept test, and the leave-one-out test.ResultsThe MR study revealed no substantial genetic correlation between serum 25(OH)D levels and PPD (OR = 1.065, 95%CI = 0.878-1.293, P = 0.522 for set A; OR = 0.978, 95 % CI = 0.669-1.430, P = 0.910 for set B). Additionally, in the reverse analysis, we did not observe a significant causal impact of PPD on serum 25(OH)D (OR = 1.001, 95%CI = 0.974-1.028, P = 0.951 for set A; OR = 1.011, 95%CI = 0.992-1.031, P = 0.261 for set B). The results obtained from MR-Egger and WME analyses concord with those derived from the IVW method. Conducting leave-one-out tests did not identify any single nucleotide polymorphism that might have influenced the MR results, confirming the robustness and reliability of the findings.ConclusionsThe results suggest the absence of a causal link between vitamin D concentrations and PPD. Inconsistent observations in previous observational studies may be attributed to residual confounding.

Dataset Information

Causal Associations of Circulating Lipids with Osteoarthritis: A Bidirectional Mendelian Randomization Study.

Publications

Causal Associations of Circulating Lipids with Osteoarthritis: A Bidirectional Mendelian Randomization Study.

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