Mendelian Randomization Focused Analysis of Vitamin D on the Secondary Prevention of Ischemic Stroke

Stroke ◽  
2021 ◽  
Author(s):  
Yap-Hang Chan ◽  
C. Mary Schooling ◽  
Jie Zhao ◽  
Shiu-Lun Au Yeung ◽  
Jo Jo Hai ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Vitamin D ◽  
Ischemic Stroke ◽  
Risk Score ◽  
Genetic Risk ◽  
Odds Ratio ◽  
Mendelian Randomization ◽  
De Novo ◽  
Genetic Risk Score ◽  
Ischemic Disease

Background and Purpose: Experimental studies showed vitamin D (Vit-D) could promote vascular regeneration and repair. Prior randomized studies had focused mainly on primary prevention. Whether Vit-D protects against ischemic stroke and myocardial infarction recurrence among subjects with prior ischemic insults was unknown. Here, we dissected through Mendelian randomization any effect of Vit-D on the secondary prevention of recurrent ischemic stroke and myocardial infarction. Methods: Based on a genetic risk score for Vit-D constructed from a derivation cohort sample (n=5331, 45% Vit-D deficient, 89% genotyped) via high-throughput exome-chip screening of 12 prior genome-wide association study–identified genetic variants of Vit-D mechanistic pathways ( rs2060793 , rs4588 , and rs7041 ; F statistic, 73; P <0.001), we performed a focused analysis on prospective recurrence of myocardial infarction (MI) and ischemic stroke in an independent subsample with established ischemic disease (n=441, all with prior first ischemic event; follow-up duration, 41.6±14.3 years) under a 2-sample, individual-data, prospective Mendelian randomization approach. Results: In the ischemic disease subsample, 11.1% (n=49/441) had developed recurrent ischemic stroke or MI and 13.3% (n=58/441) had developed recurrent or de novo ischemic stroke/MI. Kaplan-Meier analyses showed that genetic risk score predicted improved event-free survival from recurrent ischemic stroke or MI (log-rank, 13.0; P =0.001). Cox regression revealed that genetic risk score independently predicted reduced risk of recurrent ischemic stroke or MI combined (hazards ratio, 0.62 [95% CI, 0.48–0.81]; P <0.001), after adjusted for potential confounders. Mendelian randomization supported that Vit-D is causally protective against the primary end points of recurrent ischemic stroke or MI (Wald estimate: odds ratio, 0.55 [95% CI, 0.35–0.81]) and any recurrent or de novo ischemic stroke/MI (odds ratio, 0.64 [95% CI, 0.42–0.91]) and recurrent MI alone (odds ratio, 0.52 [95% CI, 0.30–0.81]). Conclusions: Genetically predicted lowering in Vit-D level is causal for the recurrence of ischemic vascular events in persons with prior ischemic stroke or MI.

scholarly journals Mendelian randomization provides evidence for a causal effect of higher serum IGF-1 concentration on risk of hip and knee osteoarthritis

Rheumatology ◽  
2020 ◽  
Author(s):  
April Hartley ◽  
Eleanor Sanderson ◽  
Lavinia Paternoster ◽  
Alexander Teumer ◽  
Robert C Kaplan ◽  
...  
Keyword(s):  
Risk Score ◽  
Genetic Risk ◽  
Odds Ratio ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Genetic Risk Score ◽  
Uk Biobank ◽  
Knee Oa ◽  
Increased Risk

Abstract Objectives How insulin-like growth factor-1 (IGF-1) is related to OA is not well understood. We determined relationships between IGF-1 and hospital-diagnosed hand, hip and knee OA in UK Biobank, using Mendelian randomization (MR) to determine causality. Methods Serum IGF-1 was assessed by chemiluminescent immunoassay. OA was determined using Hospital Episode Statistics. One-sample MR (1SMR) was performed using two-stage least-squares regression, with an unweighted IGF-1 genetic risk score as an instrument. Multivariable MR included BMI as an additional exposure (instrumented by BMI genetic risk score). MR analyses were adjusted for sex, genotyping chip and principal components. We then performed two-sample MR (2SMR) using summary statistics from Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE) (IGF-1, N = 30 884) and the recent genome-wide association study meta-analysis (N = 455 221) of UK Biobank and Arthritis Research UK OA Genetics (arcOGEN). Results A total of 332 092 adults in UK Biobank had complete data. Their mean (s.d.) age was 56.5 (8.0) years and 54% were female. IGF-1 was observationally related to a reduced odds of hand OA [odds ratio per doubling = 0.87 (95% CI 0.82, 0.93)], and an increased odds of hip OA [1.04 (1.01, 1.07)], but was unrelated to knee OA [0.99 (0.96, 1.01)]. Using 1SMR, we found strong evidence for an increased risk of hip [odds ratio per s.d. increase = 1.57 (1.21, 2.01)] and knee [1.30 (1.07, 1.58)] OA with increasing IGF-1 concentration. By contrast, we found no evidence for a causal effect of IGF-1 concentration on hand OA [0.98 (0.57, 1.70)]. Results were consistent when estimated using 2SMR and in multivariable MR analyses accounting for BMI. Conclusion We have found evidence that increased serum IGF-1 is causally related to higher risk of hip and knee OA.

A genetic risk score predicts recurrent events after myocardial infarction in young adults

2020 ◽  
Vol 73 (8) ◽  
pp. 623-631
Author(s):  
Luis M. Rincón ◽  
Marcelo Sanmartín ◽  
Gonzalo L. Alonso ◽  
José Antonio Rodríguez ◽  
Alfonso Muriel ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Young Adults ◽  
Risk Score ◽  
Genetic Risk ◽  
Recurrent Events ◽  
Genetic Risk Score

A genetic risk score predicts de novo hepatocellular carcinoma in hepatitis C cirrotic patients treated with direct-acting antivirals

2020 ◽  
Vol 73 ◽  
pp. S208-S209
Author(s):  
Elisabetta Degasperi ◽  
Enrico Galmozzi ◽  
Serena Pelusi ◽  
Roberta D’ambrosio ◽  
Roberta Soffredini ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C ◽  
Risk Score ◽  
Genetic Risk ◽  
De Novo ◽  
Genetic Risk Score ◽  
Direct Acting Antivirals ◽  
Direct Acting ◽  
De Novo Hepatocellular Carcinoma

A MYOCARDIAL INFARCTION GENETIC RISK SCORE ASSOCIATES WITH CAROTID ATHEROSCLEROSIS

2011 ◽  
Vol 29 ◽  
pp. e19
Author(s):  
V. Hamrefors ◽  
B. Hedblad ◽  
G. Engström ◽  
P. Almgren ◽  
M. Sjögren ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Risk Score ◽  
Genetic Risk ◽  
Carotid Atherosclerosis ◽  
Genetic Risk Score

scholarly journals Association of a Genetic Risk Score With Prevalent and Incident Myocardial Infarction in Subjects Undergoing Coronary Angiography

2012 ◽  
Vol 5 (4) ◽  
pp. 441-449 ◽  
Author(s):  
Riyaz S. Patel ◽  
Yan V. Sun ◽  
Jaana Hartiala ◽  
Emir Veledar ◽  
Shaoyong Su ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Angiography ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score

Abstract P259: Genetic Risk Score, Lifestyle Cardiovascular Risk Score, and Myocardial Infarction in Hispanics

Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
Mercedes Sotos-Prieto ◽  
Ana Baylin ◽  
Hannia Campos ◽  
Lu Qi ◽  
Josiemer Mattei
Keyword(s):  
Physical Activity ◽  
Risk Factors ◽  
Myocardial Infarction ◽  
Socioeconomic Status ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Lifestyle Risk Factors ◽  
Cardiovascular Risk Score ◽  
Lifestyle Risk

Background: A genetic risk score (GRS) and a lifestyle cardiovascular risk score (LCRS) have been independently associated with myocardial infarction (MI) in Hispanics. However, it is unknown if there is an interaction or a joint association between these scores. Objectives: To assess the interactive and joint associations between a GRS and a LCRS, as well as each individual lifestyle risk factor on the likelihood of MI. Methods: Data included 1534 Costa Rican adults with nonfatal acute MI and 1534 without MI participating in a case-control study. The GRS was calculated by summing the number of the top three MI-associated risk alleles. The LCRS was calculated using the estimated coefficients as weights for each lifestyle risk factors (diet, physical activity, smoking, waist:hip ratio, low or high alcohol intake, and low socioeconomic status). Conditional logistic regression was used to calculate odds ratios (OR), adjusting for age, sex, and area of residence (matching condition), and to test for interaction and joint association. Results: The multivariable OR for MI was 1.14 (95% CI 1.07, 1.22) per GRS unit and 2.72 (2.33, 3.91) per LCRS unit. Participants in the highest tertile of the GRS and highest tertile of the LCRS had higher odds of MI (5.43 [3.80, 7.76]) compared to those in the lowest category. A significant joint association was detected (p <0.0001), while the interaction term was non-significant (p=0.44). Similar results were found for the joint association between GRS and each individual lifestyle component: joint odds for highest risk category vs. lowest was 2.16 (1.53, 3.04) for diet, 1.85 (1.33, 2.59) for physical activity, 3.31 (2.45, 4.48) for smoking, 1.32 (0.92, 1.89) for alcohol, 2.84 (1.82, 4.42) for waist:hip ratio, and 1.86 (1.29, 2.69) for socioeconomic status. Conclusion: Although lifestyle risk factors and genetics contribute independently and in combination to the odds of MI, lifestyle risk factors were stronger among Costa Ricans. Efforts to improve lifestyle behaviors in this population, regardless of genetic susceptibility, may help prevent MI and related heart conditions.

Abstract P254: Genetic Risk Score for Height and the Incidence of Venous Thromboembolism: A Prospective Study

Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
Nicholas S Roetker ◽  
James S Pankow ◽  
Pamela L Lutsey ◽  
Weihong Tang ◽  
Michael A Rosenberg ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Causal Relationship ◽  
Risk Score ◽  
Genetic Risk ◽  
Mendelian Randomization ◽  
Genetic Risk Score ◽  
Statistical Significance ◽  
Body Height ◽  
Health Study ◽  
Cardiovascular Health Study

Introduction: Several observational studies have shown that taller body height is associated with greater risk of venous thromboembolism (VTE), but it is not known whether the association is causal. We used instrumental variable analysis (Mendelian randomization) to explore the causal relationship between height and VTE using a genetic risk score (GRS) for height as the instrument. Hypothesis: There is a causal relationship between taller standing height and greater risk of VTE, as demonstrated by a Mendelian randomization approach. Methods: We created a weighted GRS for height in white men and women in the Longitudinal Investigation of Thromboembolism Etiology [consisting of two longitudinal cohort studies: Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Study (CHS)] using 668 single nucleotide polymorphisms from a recently published meta-analysis. Incident hospitalized VTE events were identified and verified by physician review of medical records. We estimated the association and causal risk differences (RD) and 95% confidence intervals (CI) for VTE incidence per standard deviation (SD) increment in height (9.4 cm). The association models were adjusted for age, sex, waist circumference, and study site. Results: There were 9,137 ARIC and 3,163 CHS participants at risk for VTE at baseline and with genetic data, and they experienced 367 (ARIC) and 105 (CHS) incident VTE events over a median 22.7 and 11.8 years of follow-up, respectively. Baseline age ranges were 45-64 and 65-98 years and mean heights were 169 and 165 cm in ARIC and CHS, respectively. The GRS was a strong instrument for height (R 2 =0.08 in ARIC and R 2 =0.07 in CHS) and had little to no correlation with other measured VTE risk factors (all R 2 ≤0.01). In ARIC, taller height was associated with greater risk of VTE [association VTE RD: 1.0% per SD in height (95% CI: 0.3 to 1.6%)]. The causal RD had the same magnitude as the association RD, but did not quite reach statistical significance [causal VTE RD per SD in height: 1.1% (95% CI: -0.3 to 2.5%)]. Predicted risks of VTE at the 10th and 90th percentiles of height (157 and 181 cm) were 2.6% and 5.4%, respectively, representing more than a doubling of risk. There was no association between height and VTE risk in CHS [association VTE RD per SD in height: 0.1% (95% CI: -1.0 to 1.2%); causal VTE RD per SD in height: -0.3% (95% CI: -2.5 to 1.9%)]. Conclusion: Taller height was associated with greater VTE risk with some supporting causal evidence in middle-aged adults from ARIC, but there was no relation between height and VTE in older adults from CHS. Future studies should further explore the causal relation between height and VTE among different age groups.

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