Dataset Information

A Mendelian Randomization Analysis to Expose the Causal Effect of IL-18 on Osteoporosis Based on Genome-Wide Association Study Data.

ABSTRACT: Accumulating evidence showed that Interleukin (IL) level is associated with Osteoporosis. Whereas, most of these associations are based on observational studies. Thus, their causality was still unclear. Mendelian randomization (MR) is a widely used statistical framework that uses genetic instrumental variables (IVs) to explore the causality of intermediate phenotype with disease. To classify their causality, we conducted a MR analysis to investigate the effect of IL-18 level on the risk of Osteoporosis. First, based on summarized genome-wide association study (GWAS) data, 8 independent IL-18 SNPs reaching genome-wide significance were deemed as IVs. Next, Simple median method was used to calculate the pooled odds ratio (OR) of these 8 SNPs for the assessment of IL-8 on the risk of Osteoporosis. Then, MR-Egger regression was utilized to detect potential bias due to the horizontal pleiotropy of these IVs. As a result of simple median method, we get the SE (-0.001; 95% CI-0.002 to 0; P = 0.042), which means low IL-18 level could increases the risk of the development of Osteoporosis. The low intercept (0; 95% CI -0.001 to 0; P = 0.59) shows there is no bias due to the horizontal pleiotropy of the IVs.

SUBMITTER: Kou N

PROVIDER: S-EPMC7099043 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A Mendelian Randomization Analysis to Expose the Causal Effect of IL-18 on Osteoporosis Based on Genome-Wide Association Study Data.

Kou Ni N Zhou Wenyang W He Yuzhu Y Ying Xiaoxia X Chai Songling S Fei Tao T Fu Wenqi W Huang Jiaqian J Liu Huiying H

Frontiers in bioengineering and biotechnology 20200320

Accumulating evidence showed that Interleukin (IL) level is associated with Osteoporosis. Whereas, most of these associations are based on observational studies. Thus, their causality was still unclear. Mendelian randomization (MR) is a widely used statistical framework that uses genetic instrumental variables (IVs) to explore the causality of intermediate phenotype with disease. To classify their causality, we conducted a MR analysis to investigate the effect of IL-18 level on the risk of Osteo ...[more]

PMID: 32266232

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Project description:BACKGROUND:Age at menarche has been associated with various health outcomes. We aimed to identify potential causal effects of age at menarche on health-related traits in a hypothesis-free manner. METHODS:We conducted a Mendelian randomization phenome-wide association study (MR-pheWAS) of age at menarche with 17,893 health-related traits in UK Biobank (n?=?181,318) using PHESANT. The exposure of interest was the genetic risk score for age at menarche. We conducted a second MR-pheWAS after excluding SNPs associated with BMI from the genetic risk score, to examine whether results might be due to the genetic overlap between age at menarche and BMI. We followed up a subset of health-related traits to investigate MR assumptions and seek replication in independent study populations. RESULTS:Of the 17,893 tests performed in our MR-pheWAS, we identified 619 associations with the genetic risk score for age at menarche at a 5% false discovery rate threshold, of which 295 were below a Bonferroni-corrected P value threshold. These included potential effects of younger age at menarche on lower lung function, higher heel bone-mineral density, greater burden of psychosocial/mental health problems, younger age at first birth, higher risk of childhood sexual abuse, poorer cardiometabolic health, and lower physical activity. After exclusion of variants associated with BMI, the genetic risk score for age at menarche was related to 37 traits at a 5% false discovery rate, of which 29 were below a Bonferroni-corrected P value threshold. We attempted to replicate findings for bone-mineral density, lung function, neuroticism, and childhood sexual abuse using 5 independent cohorts/consortia. While estimates for lung function, higher bone-mineral density, neuroticism, and childhood sexual abuse in replication cohorts were consistent with UK Biobank estimates, confidence intervals were wide and often included the null. CONCLUSIONS:The genetic risk score for age at menarche was related to a broad range of health-related traits. Follow-up analyses indicated imprecise evidence of an effect of younger age at menarche on greater bone-mineral density, lower lung function, higher neuroticism score, and greater risk of childhood sexual abuse in the smaller replication samples available; hence, these findings need further exploration when larger independent samples become available.

Dataset Information

A Mendelian Randomization Analysis to Expose the Causal Effect of IL-18 on Osteoporosis Based on Genome-Wide Association Study Data.

Publications

A Mendelian Randomization Analysis to Expose the Causal Effect of IL-18 on Osteoporosis Based on Genome-Wide Association Study Data.

Similar Datasets

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