Author Of 1 Presentation
P0467 - Hypertension, cholesterol levels, and Type II Diabetes are not associated with multiple sclerosis risk: Mendelian randomization analyses (ID 1473)
Abstract
Background
Multiple sclerosis (MS) is a multi-factorial neurodegenerative, autoimmune disease. Higher body-mass index is an established risk factor for MS. The causal impact of other cardiometabolic conditions on MS risk are not known, including hypertension (HTN), hyperlipidemia (CHOL), and Type II Diabetes (T2D).
Objectives
To examine the causal impact of HTN, CHOL, and T2D, as well as variation in continuous measures of blood pressure and cholesterol levels, on risk of MS.
Methods
Two-sample Mendelian randomization (2SMR) was performed to investigate the causal contribution of HTN, CHOL, and T2D on MS risk. 2SMR is a causal inference approach where genetic variants associated with an exposure are used as instrumental variables for the exposure, to be tested for association in the outcome of interest. The Wald ratio of exposure and outcome effect estimates for each variant are then combined via meta-analysies to determine overall causal effects. We performed 2SMR using multiple summary statistics from multiple genome-wide association studies (GWAS) for all exposure-outcome combinations, including 4 MS GWAS (n=463,010; n=38,589; n=27,098; n=2,739), 1 GWAS of diastolic blood pressure (DBP) (n=317,756), 1 GWAS of systolic blood pressure (SBP) (n=317,754), 2 GWAS of HTN (n=337,199; n=337,159), 2 GWAS of high-density lipoprotein (HDL) (n=187,176; n=21,555), 2 GWAS of low-density lipoprotein (LDL) (n=173,082; n=21,559), and 2 GWAS of T2D (n=149,821; n=337,159). All 2SMR analyses were adjusted for horizontal pleiotropy using the Egger regression approach. Clumping was performed for each exposure GWAS to prune variants for LD in 10kb windows. LD proxies in the outcome GWAS were set at an r2 value of 0.8 or higher.
Results
Overall, there was no evidence to suggest causal associations between HTN, SBP, DBP, HDL, LDL, or T2D on MS risk. Neither SBP nor DBP was associated with MS risk (pmin=0.38, 0.26, β=-0.001, 0.60, respectively). HTN as a binary measure was similarly not associated across the various studies (pmin=0.21, β=-6.77). HDL and LDL were not associated with MS (pmin=0.25, 0.07, β=0.17, 0.26, respectively). And lastly, T2D was also not associated with MS (pmin=0.51, β=0.06).
Conclusions
Blood pressure variation, HTN, lipid levels, and T2D do not appear to have a genetically-driven association with MS risk. Considering the relationships between BMI and MS, and BMI and these other cardiometabolic traits, further research is necessary to disentangle the mechanisms through which BMI confers risk for MS.
Presenter Of 1 Presentation
P0467 - Hypertension, cholesterol levels, and Type II Diabetes are not associated with multiple sclerosis risk: Mendelian randomization analyses (ID 1473)
Abstract
Background
Multiple sclerosis (MS) is a multi-factorial neurodegenerative, autoimmune disease. Higher body-mass index is an established risk factor for MS. The causal impact of other cardiometabolic conditions on MS risk are not known, including hypertension (HTN), hyperlipidemia (CHOL), and Type II Diabetes (T2D).
Objectives
To examine the causal impact of HTN, CHOL, and T2D, as well as variation in continuous measures of blood pressure and cholesterol levels, on risk of MS.
Methods
Two-sample Mendelian randomization (2SMR) was performed to investigate the causal contribution of HTN, CHOL, and T2D on MS risk. 2SMR is a causal inference approach where genetic variants associated with an exposure are used as instrumental variables for the exposure, to be tested for association in the outcome of interest. The Wald ratio of exposure and outcome effect estimates for each variant are then combined via meta-analysies to determine overall causal effects. We performed 2SMR using multiple summary statistics from multiple genome-wide association studies (GWAS) for all exposure-outcome combinations, including 4 MS GWAS (n=463,010; n=38,589; n=27,098; n=2,739), 1 GWAS of diastolic blood pressure (DBP) (n=317,756), 1 GWAS of systolic blood pressure (SBP) (n=317,754), 2 GWAS of HTN (n=337,199; n=337,159), 2 GWAS of high-density lipoprotein (HDL) (n=187,176; n=21,555), 2 GWAS of low-density lipoprotein (LDL) (n=173,082; n=21,559), and 2 GWAS of T2D (n=149,821; n=337,159). All 2SMR analyses were adjusted for horizontal pleiotropy using the Egger regression approach. Clumping was performed for each exposure GWAS to prune variants for LD in 10kb windows. LD proxies in the outcome GWAS were set at an r2 value of 0.8 or higher.
Results
Overall, there was no evidence to suggest causal associations between HTN, SBP, DBP, HDL, LDL, or T2D on MS risk. Neither SBP nor DBP was associated with MS risk (pmin=0.38, 0.26, β=-0.001, 0.60, respectively). HTN as a binary measure was similarly not associated across the various studies (pmin=0.21, β=-6.77). HDL and LDL were not associated with MS (pmin=0.25, 0.07, β=0.17, 0.26, respectively). And lastly, T2D was also not associated with MS (pmin=0.51, β=0.06).
Conclusions
Blood pressure variation, HTN, lipid levels, and T2D do not appear to have a genetically-driven association with MS risk. Considering the relationships between BMI and MS, and BMI and these other cardiometabolic traits, further research is necessary to disentangle the mechanisms through which BMI confers risk for MS.