scholarly journals Genetic Contributors of Incident Stroke in 10,700 African Americans With Hypertension: A Meta-Analysis From the Genetics of Hypertension Associated Treatments and Reasons for Geographic and Racial Differences in Stroke Studies

2021 ◽  
Vol 12 ◽  
Author(s):  
Nicole D. Armstrong ◽  
Vinodh Srinivasasainagendra ◽  
Amit Patki ◽  
Rikki M. Tanner ◽  
Bertha A. Hidalgo ◽  
...  
Keyword(s):  
Risk Factors ◽  
At Risk ◽  
African Americans ◽  
Racial Differences ◽  
Predictive Accuracy ◽  
Reference Model ◽  
Meta Analysis ◽  
Ancestral Population ◽  
Polygenic Risk Score ◽  
Clinical Tools

Background: African Americans (AAs) suffer a higher stroke burden due to hypertension. Identifying genetic contributors to stroke among AAs with hypertension is critical to understanding the genetic basis of the disease, as well as detecting at-risk individuals.Methods: In a population comprising over 10,700 AAs treated for hypertension from the Genetics of Hypertension Associated Treatments (GenHAT) and Reasons for Geographic and Racial Differences in Stroke (REGARDS) studies, we performed an inverse variance-weighted meta-analysis of incident stroke. Additionally, we tested the predictive accuracy of a polygenic risk score (PRS) derived from a European ancestral population in both GenHAT and REGARDS AAs aiming to evaluate cross-ethnic performance.Results: We identified 10 statistically significant (p < 5.00E-08) and 90 additional suggestive (p < 1.00E-06) variants associated with incident stroke in the meta-analysis. Six of the top 10 variants were located in an intergenic region on chromosome 18 (LINC01443-LOC644669). Additional variants of interest were located in or near the COL12A1, SNTG1, PCDH7, TMTC1, and NTM genes. Replication was conducted in the Warfarin Pharmacogenomics Cohort (WPC), and while none of the variants were directly validated, seven intronic variants of NTM proximal to our target variants, had a p-value <5.00E-04 in the WPC. The inclusion of the PRS did not improve the prediction accuracy compared to a reference model adjusting for age, sex, and genetic ancestry in either study and had lower predictive accuracy compared to models accounting for established stroke risk factors. These results demonstrate the necessity for PRS derivation in AAs, particularly for diseases that affect AAs disproportionately.Conclusion: This study highlights biologically plausible genetic determinants for incident stroke in hypertensive AAs. Ultimately, a better understanding of genetic risk factors for stroke in AAs may give new insight into stroke burden and potential clinical tools for those among the highest at risk.

scholarly journals Racial Differences in Hepatocellular Carcinoma Incidence and Risk Factors among a Low Socioeconomic Population

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3710
Author(s):  
Sylvie Muhimpundu ◽  
Rebecca Baqiyyah N. Conway ◽  
Shaneda Warren Andersen ◽  
Loren Lipworth ◽  
Mark D. Steinwandel ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Cohort Study ◽  
African Americans ◽  
Racial Differences ◽  
Prospective Cohort ◽  
White Americans ◽  
Low Socioeconomic ◽  
Factors Associated ◽  
Southeastern Us

The purpose of this study was to examine differences in risk factors associated with hepatocellular carcinoma (HCC) among White and African Americans from low socioeconomic backgrounds in the Southern Community Cohort Study (SCCS). The SCCS is a prospective cohort study with participants from the southeastern US. HCC incidence rates were calculated. Multivariable Cox regression was used to calculate HCC-adjusted hazard ratios (aHR) associated with known baseline HCC risk factors for White and African Americans, separately. There were 294 incident HCC. The incidence rate ratio for HCC was higher (IRR = 1.4, 95%CI: 1.1–1.9) in African Americans compared to White Americans. White Americans saw a stronger association between self-reported hepatitis C virus (aHR = 19.24, 95%CI: 10.58–35.00) and diabetes (aHR = 3.55, 95%CI: 1.96–6.43) for the development of HCC compared to African Americans (aHR = 7.73, 95%CI: 5.71–10.47 and aHR = 1.48, 95%CI: 1.06–2.06, respectively) even though the prevalence of these risk factors was similar between races. Smoking (aHR = 2.91, 95%CI: 1.87–4.52) and heavy alcohol consumption (aHR = 1.59, 95%CI: 1.19–2.11) were significantly associated with HCC risk among African Americans only. In this large prospective cohort, we observed racial differences in HCC incidence and risk factors associated with HCC among White and African Americans.

Abstract P029: Racial Differences in Sudden Cardiac Death: Findings From the Atherosclerosis Risk in Communities Study (ARIC)

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Di Zhao ◽  
Eliseo Guallar ◽  
Elena Blasco-Colmenares ◽  
Nona Sotoodehnia ◽  
Wendy Post
Keyword(s):  
Risk Factors ◽  
African Americans ◽  
Sudden Cardiac Death ◽  
Racial Differences ◽  
Cardiac Death ◽  
Large Scale ◽  
Community Dwelling ◽  
Mediation Effect ◽  
P Value ◽  
Expert Committee

Background: In hospital-based studies and in studies of participants with pre-existing conditions, African Americans have a higher risk of in- and out-of-hospital sudden cardiac death (SCD) compared with Whites. However, the risk of SCD of African Americans and Whites has never been compared in large-scale community-based cohort studies. Objective: To compare the risk of SCD among African Americans and Whites, and to evaluate the risk factors that may explain racial differences in incidence. Methods: Cohort study of 3,838 African Americans and 11,245 Whites participating in ARIC. Race was self-reported. SCD cases were defined as a sudden pulseless condition from a cardiac cause in a previously stable individual and adjudicated by an expert committee. Mediation effect of covariates was calculated using boot-strapping method. Cox proportional hazards models were adjusted for demographics, social economic status, cardiovascular (CVD), and electrocardiographic risk factors. Results: The mean (SD) age was 53.6 (5.8) for African Americans and 54.4 (5.7) years for Whites. During 25.3 years of follow-up, 215 African Americans and 332 Whites experienced SCD. In multivariable-adjusted models, the HRs (95% CI) for SCD comparing African Americans and Whites were 1.70 (1.37, 2.10) overall, 2.00 (1.40, 2.84) in women, and 1.46 (1.10, 1.92) in men (p-value for race by sex interaction 0.02; Table ). CVD and electrocardiographic risk factors explained 36.6% (21.4, 51.8%) of the excess risk of SCD in African Americans, with a large proportion of racial differences unexplained. Conclusions: The risk of SCD in community-dwelling African Americans was significantly higher than in Whites, particularly among women. CVD risk factors, including higher prevalence of obesity, diabetes, hypertension and LV hypertrophy in African Americans, explained only a small fraction of this difference. Further research is needed to identify factors responsible for race differences in SCD and to implement prevention strategies in high-risk minorities.

Association of Sickle Cell Trait with Risk of Coronary Heart Disease in African Americans

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 11-11 ◽  
Author(s):  
Hyacinth I Hyacinth ◽  
Carty L Cara ◽  
Samantha R Seals ◽  
Marguerite R. Irvin ◽  
Rakhi P. Naik ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
African Americans ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Meta Analysis ◽  
Significant Heterogeneity ◽  
Crude Incidence Rate ◽  
Crude Incidence

Abstract Background The incidence of and mortality from coronary heart disease (CHD) is significantly higher among African Americans (AAs) compared to Whites, even after adjusting for traditional CHD risk factors. Studies suggests that the unexplained excess risk might be the result of genetic modifiers associated with African ancestry conferring a higher risk of CHD. One such gene variant is the sickle cell mutation. The heterozygous state, or sickle cell trait (SCT), with a prevalence of 8 - 12% among AAs, was previously deemed clinically benign; however, recent evidence indicates that SCT is associated with increased risk of chronic kidney disease venous thromboembolism and sudden death following exertion. Individuals with SCT have higher circulating levels of C-reactive protein, fibrinogen, prothrombin fragment 1.2 and D-dimer. We hypothesized that AAs with SCT have a higher risk for myocardial infarction (MI) and coronary heart disease (CHD) than AAs who are homozygous for wild-type hemoglobin. Methods We obtained genotype and phenotype data from the Women's Health Initiative (WHI) REasonsfor Geographic and Racial Differences in Stroke (REGARDS), Multi-Ethnic Study of Atherosclerosis (MESA), Jackson Heart Study (JHS) and Atherosclerosis Risk In Communities (ARIC) cohorts. The outcomes were incident MI or CHD. Incident MI was defined as adjudicated non-fatal or fatal MI, while incident CHD was defined as 1) adjudicated non-fatal MI, 2) fatal MI, 3) documented coronary revascularization procedures or 4) non-MI CHD death. SCT status was determined by either direct genotyping or imputation for rs334 using the 1000Genome reference panel. Homozygous individuals and those with a prior history of CHD were excluded. Individuals with incident “micro MI”, only defined in REGARDS, were also excluded from the analysis. Analysis was performed separately in each cohort using a Cox proportional hazard models to estimate the hazard ratio (HR) for incident MI or CHD comparing SCT carriers to non-carriers. Models in each cohort were adjusted for age, sex, study site or region of residence, hypertension or systolic blood pressure, diabetes, serum LDL or HDL or total cholesterol, and population stratification (using principal components of global ancestry). The results from each cohorts were then meta-analyzed using a random effect model due to significant heterogeneity between studies (I2 = 39.1%, p = 0.02 for MI meta-analysis and I2 = 56%, p = 0.01 for CHD meta-analysis). Results A total of 20,053 African American men and women were included in the combined sample; 1503 with SCT (7.5% prevalence). Average ages in years at baseline were: 65.0±6.0 in WHI (N = 2248), 62.0 ± 9.2 in REGARDS (N = 10573); 62.2±10.2 in MESA (N = 1556); 50.0 ± 11.9 in JHS (N = 2133); and 54.0 ± 6.0 in ARIC (N = 3543). There were no statistically significant differences in the distribution of traditional cardiovascular risk factors by SCT status within cohorts, except that atrial fibrillation was more prevalent among REGARDS participants with SCT compared to those without SCT (9.9% vs. 7.8%, p = 0.03). The crude incidence rate of MI per 1000 person years in those with SCT compared to those without SCT was: 4.0 vs. 5.2 in WHI; 5.7 vs. 5.0 in REGARDS; 5.8 vs 4.3 in MESA, 2.0 vs 2.1 in JHS; and 4.1 vs 5.9 in ARIC. For CHD, the crude incidence rate was: 5.8 vs. 7.2 in WHI, 8.9 vs. 7.4 in REGARDS; 15.4 vs. 6.4 in MESA; 3.4 vs. 3.4 in JHS; and 10.5 vs. 9.5 in ARIC. The HR (95% CI) for MI was: 0.96 (0.49 - 1.89) in WHI; 1.27 (0.8 - 2.0) in REGARDS; 1.84 (0.74 - 4.60) in MESA; 1.24 (0.28 - 5.44) in JHS; and 0.68 (0.42 - 1.10) in ARIC. And that for CHD was: 1.05 (0.63 - 1.74) in WHI; 1.49 (1.01 - 2.18) in REGARDS; 2.82 (1.48 - 5.38) in MESA; 1.45 (0.50 - 4.19) in JHS; and 1.10 (0.80 - 1.50) in ARIC. Meta-analysis showed that, while SCT status was not significantly associated with incident MI (1.10 [0.73 - 1.64]), it was significantly associated with incident CHD (1.42 [1.02 - 1.98] Figures 1a and 1b). Conclusions This study showed a significant association between SCT and incident CHD, but not MI. Our conclusion is limited by the significant heterogeneity that existed between studies. Since SCT status was not associated with MI, but was associated with CHD, further work is needed to confirm these findings, determine which CHD component(s) explain the observed association and elucidate the possible mechanism(s) involved. Disclosures No relevant conflicts of interest to declare.

scholarly journals Predicting suicide following self-harm: systematic review of risk factors and risk scales

2016 ◽  
Vol 209 (4) ◽  
pp. 277-283 ◽  
Author(s):  
Melissa K. Y. Chan ◽  
Henna Bhatti ◽  
Nick Meader ◽  
Sarah Stockton ◽  
Jonathan Evans ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Suicide Ideation ◽  
Predictive Accuracy ◽  
Meta Analysis ◽  
Mental Healthcare ◽  
Sufficient Evidence ◽  
Predictive Values ◽  
Self Harm ◽  
The Individual

BackgroundPeople with a history of self-harm are at a far greater risk of suicide than the general population. However, the relationship between self-harm and suicide is complex.AimsTo undertake the first systematic review and meta-analysis of prospective studies of risk factors and risk assessment scales to predict suicide following self-harm.MethodWe conducted a search for prospective cohort studies of populations who had self-harmed. For the review of risk scales we also included studies examining the risk of suicide in people under specialist mental healthcare, in order to broaden the scope of the review and increase the number of studies considered. Differences in predictive accuracy between populations were examined where applicable.ResultsTwelve studies on risk factors and 7 studies on risk scales were included. Four risk factors emerged from the metaanalysis, with robust effect sizes that showed little change when adjusted for important potential confounders. These included: previous episodes of self-harm (hazard ratio (HR) = 1.68, 95% CI 1.38–2.05, K = 4), suicidal intent (HR = 2.7, 95% CI 1.91–3.81, K = 3), physical health problems (HR = 1.99, 95% CI 1.16–3.43, K = 3) and male gender (HR = 2.05, 95% CI 1.70–2.46, K = 5). The included studies evaluated only three risk scales (Beck Hopelessness Scale (BHS), Suicide Intent Scale (SIS) and Scale for Suicide Ideation). Where meta-analyses were possible (BHS, SIS), the analysis was based on sparse data and a high heterogeneity was observed. The positive predictive values ranged from 1.3 to 16.7%.ConclusionsThe four risk factors that emerged, although of interest, are unlikely to be of much practical use because they are comparatively common in clinical populations. No scales have sufficient evidence to support their use. The use of these scales, or an over-reliance on the identification of risk factors in clinical practice, may provide false reassurance and is, therefore, potentially dangerous. Comprehensive psychosocial assessments of the risks and needs that are specific to the individual should be central to the management of people who have self-harmed.

Weight, BMI and stability are risk factors associated with lateral ankle sprains and chronic ankle instability: a meta-analysis

2019 ◽  
Vol 4 (6) ◽  
pp. 313-327
Author(s):  
Gwendolyn Vuurberg ◽  
Nienke Altink ◽  
Morteza Rajai ◽  
Leendert Blankevoort ◽  
Gino M M J Kerkhoffs
Keyword(s):  
Risk Factors ◽  
At Risk ◽  
Ankle Instability ◽  
Meta Analysis ◽  
Ankle Sprains ◽  
Healthy Controls ◽  
Lateral Ankle ◽  
Intrinsic Factors ◽  
Factors Associated

ImportanceLateral ankle sprains (LAS) are common in the general population and may lead to chronic ankle instability (CAI). If patients at risk could be identified, they could receive adequate and on-time treatment.ObjectiveThe purpose of the current review was to identify all reported intrinsic factors associated with sustaining a LAS or progressing to CAI after an initial sprain.Evidence reviewPubMed, Embase, MEDline, Cochrane and PEDro were searched for studies published until July 2019. Articles were selected if they included intrinsic factors related to LAS or CAI, subjects of at least 16 years old, and contained a minimum of 10 patients and 10 controls. Studies were excluded if they concerned reviews or case reports, included patients with previous surgical interventions, concomitant injuries or joint pathology other than ankle instability. Quality of included studies was assessed using the Quality in Prognostic Studies tool and quality of evidence was assessed using the GRADEpro tool. In case outcomes were described by at least three studies, data were pooled and assessed by performing a meta-analysis. Based on the pooled data, either a fixed-effects model or random-effects model was selected to correct for the degree of heterogeneity.FindingsThe search resulted in a total of 4154 studies. After title and abstract screening and subsequent full-text screening, 80 relevant studies were included. Results of the meta-analyses indicated that, compared with healthy controls, patients with LAS had a higher mean body mass index (BMI). In patients with CAI, a higher weight and a longer time to stabilise after performing a task (eg, jumping) were found compared with healthy controls. Other outcomes could not be compared using a meta-analysis due to heterogeneity in outcome measurement and the great number of different outcomes reported. Identification of the risk factors when patients present themselves after a LAS may help to determine which patients are at risk of recurrent sprains or developing CAI.Conclusions and relevanceBased on the findings in this review, a higher BMI, and a higher weight and neuromuscular stability deficits may be regarded risk factors for sustaining a LAS or developing CAI, respectively.Level of evidenceIII.

scholarly journals CHD Risk Factors In African-Americans

Circulation ◽  
2001 ◽  
Vol 103 (suppl_1) ◽  
pp. 1347-1347
Author(s):  
Daniel W Jones ◽  
Lloyd E Chambless ◽  
Aaron R Folsom ◽  
Richard G Hutchinson ◽  
Richey A Sharrett ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Heart Disease ◽  
Risk Factor ◽  
Heart Disease ◽  
Black Women ◽  
African Americans ◽  
Racial Differences ◽  
Ldl Cholesterol ◽  
Traditional Risk Factors ◽  
Chd Risk Factors

0017 Few studies have reported the incidence of coronary heart disease and its relationship to risk factors in African-Americans. As part of the Atherosclerosis Risk in Communities Study, baseline risk factors were tested as predictors of incident coronary heart disease over 7-10 years of follow-up, 1987-1997, in four U.S. communities (Forsyth County, North Carolina; Jackson, Mississippi; Minneapolis, Minnesota; and Washington County, Maryland). The sample included 14,026 men and women (2,298 black women [BW]; 5,686 white women [WW]; 1,396 black men [BM]; and 4,682 white men [WM] aged 45-64 who were free of clinical coronary heart disease at baseline. Age-adjusted incidence rates for the 7-10 year period (95% confidence interval) for coronary heart disease were BW 5.0(4.1-6.1), WW 4.0(3.5-4.6), BM 10.7(8.9-12.8), and WM 12.6(11.5-13.8). In multivariate analysis, traditional risk factors were generally predictive in blacks as in whites. Hypertension was a particularly strong risk factor in black women, with hazard rate ratios (HR) being: BW 4.12, WW 2.0, BM 1.85, and WM 1.59. Diabetes was predictive, but HRs were somewhat less in blacks than in whites: BW 1.88, WW 3.34, BM 1.70, and WW 2.14. LDL cholesterol was similarly predictive in all race/gender groups, HR 1.19-1.36 per S.D. LDL cholesterol increment. HDL cholesterol appeared somewhat more protective in whites than in blacks. Although black/white differences in risk factor associations exist, there were more similarities than differences in coronary heart disease risk factors and incidence. Findings from this study, along with clinical trial evidence showing efficacy, support aggressive management of traditional risk factors in blacks as in whites. Understanding of the intriguing racial differences in risk factor prediction may be an important part of further understanding the causes of coronary heart disease and may lead to better methods of prevention and treatment.

scholarly journals Racial Differences in Sexual Dysfunction Among Postdeployed Iraq and Afghanistan Veterans

2013 ◽  
Vol 7 (5) ◽  
pp. 374-381 ◽  
Author(s):  
G. M. Monawar Hosain ◽  
David M. Latini ◽  
Michael R. Kauth ◽  
Heather Honoré Goltz ◽  
Drew A. Helmer
Keyword(s):  
Risk Factors ◽  
Posttraumatic Stress Disorder ◽  
African Americans ◽  
Sexual Dysfunction ◽  
Marital Status ◽  
Posttraumatic Stress ◽  
Racial Differences ◽  
Stress Disorder ◽  
Race Ethnicity ◽  
Chi Square Analysis

This study examined the racial/ethnic differences in prevalence and risk factors of sexual dysfunction among postdeployed Iraqi/Afghanistan veterans. A total of 3,962 recently deployed veterans were recruited from Houston Veterans Affairs medical center. The authors examined sociodemographic, medical, mental-health, and lifestyle-related variables. Sexual dysfunction was diagnosed by ICD9-CM code and/or medicines prescribed for sexual dysfunction. Analyses included chi-square, analysis of variance, and multivariate logistic regression. Sexual dysfunction was observed 4.7% in Whites, 7.9% in African Americans, and 6.3% in Hispanics. Age, marital status, smoking, and hypertension were risk factors for Whites, whereas age, marital status, posttraumatic stress disorder and hypertension were significant for African Americans. For Hispanics, only age and posttraumatic stress disorder were significant. This study identified that risk factors of sexual dysfunction varied by race/ethnicity. All postdeployed veterans should be screened; and psychosocial support and educational materials should address race/ethnicity-specific risk factors.

Abstract P227: Depressive Symptoms and Incident CHD among African Americans and Whites: The Reasons for Geographical and Racial Differences in Stroke (REGARDS) Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Mario Sims ◽  
Nicole Redmond ◽  
Yulia Khodneva ◽  
Raegan Durant ◽  
Jewell Halanych ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Depressive Symptoms ◽  
African Americans ◽  
Racial Disparities ◽  
Racial Differences ◽  
Community Dwelling ◽  
Chd Risk ◽  
Regards Study ◽  
Chd Risk Factors

Objectives: African Americans (AA) have higher risk for coronary heart disease (CHD) outcomes than Whites. This racial disparity has been attributed to differences in risk factors such as hypertension, diabetes, smoking, and inactivity. Depression has been associated with CHD risk, both through behavioral factors and possibly through more direct mechanisms. Yet, the role of depressive symptoms in racial disparities in risk of CHD is not clear. Using the REGARDS Study, we examined the association between depressive symptoms and incident CHD. Hypothesis: Depressive symptoms are associated with incident CHD among AA, but not Whites. Methods: REGARDS is a national cohort of US community-dwelling adults aged >45 recruited from 2003 to 2007. Longitudinal associations of depressive symptoms with incident acute CHD (fatal CHD or nonfatal myocardial infarction or coronary revascularization) by race were examined among 24,261 participants (AA = 10,265; Whites =13,996) free of CHD at baseline, and observed through 12/31/09. Baseline depressive symptoms were defined by the 4-item Centers for Epidemiological Studies Depression Scale (CES-D), with continuous scores (0-12 range) dichotomized as normal (<4) or depressive symptoms (≥4). We estimated multivariable Cox proportional hazards models of incident CHD with depressive symptoms, adjusting for sociodemographics, CHD risk factors and health behaviors. Results: Overall mean follow-up was 4.2+1.5 years, CHD incidence was 8.3 events per 1000 person-years (n=366 events) among AA and 8.8 events per 1000 person-years (n=613 events) among Whites, p=0.0015. Depressive symptoms were more prevalent among AA (13.1%) than among Whites (8.5%), p<0.001. There was a significant interaction between race and depressive symptoms, thus models were stratified on race. After adjustment for age, sex, marital status and region, depressive symptoms were significantly associated with incident CHD among AA (HR 1.57 {95% CI 1.18-2.09}) but not among Whites (HR 1.11 {0.80-1.56}). After adding education, income, physical activity, smoking, alcohol consumption, diabetes, BMI, CRP, systolic blood pressure, cholesterol, albuminuria, use of blood pressure or statin medications, the relationship for AA was modestly attenuated but still significant (HR 1.35 {95% CI 1.01-1.81}). Conclusions: Depressive symptoms were associated with risk of incident CHD among AA but not Whites. Efforts to reduce racial disparities in CHD may need to address environmental and psychosocial factors that place AA at higher risk.

Abstract P091: Ethnic Disparities in Social and Psychosocial Factors Modify the Effect of Genes on Body Mass Index

Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
Erin B Ware ◽  
Jennifer A Smith ◽  
Jessica Faul ◽  
Sharon L Kardia
Keyword(s):  
Risk Factors ◽  
Social Support ◽  
Body Mass Index ◽  
African Americans ◽  
Life Events ◽  
Body Mass ◽  
Socioeconomic Position ◽  
Stressful Life Events ◽  
Meta Analysis ◽  
Gene Region

Introduction: Obesity/body mass index (BMI) is one of the leading risk factors of cardiovascular disease (CVD) in both African American and non-Hispanic white populations. Identifying the range of factors that lead to the persistent and pronounced differences in the BMI of populations is critical for developing effective strategies for reducing these inequalities and ultimately reducing the incidence of CVD. It is posited that these differences arise from the interplay between both biological (genes) and social factors (environments). Standard approaches to this complex problem of incorporating “bio-social” data remain fractured; examining only biological, or only social determinants of the diseases/risk factors in question. This paradigm is not effective in uncovering the origins of diseases that arise from the relationships between multiple systems. By incorporating both biological and sociological data, we seek to better understand the health disparities underlying obesity. Hypotheses: We hypothesize that there will be gene regions associated with BMI in both African and non-Hispanic whites, but not necessarily the same regions across ethnicity. We expect stronger associations in each ethnicity with gene regions defined from meta-analysis of that ethnicity. We hypothesize that low socioeconomic position, lower levels of social support and higher levels of anger, ongoing stressful life events, and depressive symptoms will modify the effects of genetic predictors on BMI. Methods: We used novel, gene region-based analysis methods (Sequence Kernel Association Testing and Gene-Environment Set Association Test) with gene regions identified from 103 known obesity loci (97 from published GWAS meta-analysis in European ancestry and 6 from African ancestry), to examine the effect of gene regions on BMI in up to 3,000 African Americans and up to 12,000 non-Hispanic whites from the Health and Retirement Study. We also investigated the modification of these gene regions’ effects on BMI by social and psychosocial environment and compared across ethnicity. Results and Conclusions: Preliminary results indicate strong gene-region associations in African Americans with several genes including GPRC5B (p=0.024), SH2B1 (p=0.016) and TNNI3K (p=0.004) as well as statistically significant associations between BMI and social/psychosocial variables (bivariate p<0.01 for anger, social support, socioeconomic position, stressful life events and depression scores in non-Hispanic whites; depression score in African Americans). Gene-region results in the non-Hispanic whites and interaction results are forthcoming. In conclusion, investigating gene-by-psychosocial and gene-by-socioeconomic interactions for one of the most important risk factors for chronic diseases in older adults could help motivate new bridges to be built between biological and social scientists.

Abstract P613: Genetic Risk of Vascular Risk Factors and Severity of Leukoaraiosis in Patients With Ischemic Stroke: The MRI-GENIE Study

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Huichun Xu ◽  
Brady Gaynor ◽  
Kathleen Ryan ◽  
Patrick McArdle ◽  
Martin Bretzner ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Ischemic Stroke ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Large Population ◽  
Vascular Risk Factors ◽  
P Value ◽  
Polygenic Risk Score ◽  
Vascular Risk

Introduction: Severity of leukoaraiosis detected on T2 MRI scans as white matter hyperintensities (WMH) is associated with infarct growth and poor poststroke outcomes in patients with acute ischemic stroke (AIS). Traditional vascular risk factors (VRF) such as age, hypertension (HTN), type 2 diabetes mellitus (T2D), and cigarette smoking are linked to WMH in large population-based studies, yet casual inferences for WMH in AIS patients are limited. We sought to examine the VRFs for evidence of causal relationships with WMH burden in AIS patients using mendelian randomization principles and polygenic risk score (PRS) methods. Method: We examined FLAIR MRIs obtained within 48 hours of AIS onset in 4,362 European Caucasian patients from the MRI-GENetics Interface Exploration (MRI-GENIE) study. WMH volume (WMHv) was measured using a fully automated deep-learning trained algorithm. We considered 13 VRFs: blood pressure (HTN, SBP, DBP, Pulse Pressure), lipid (total cholesterol, HDL, LDL, TG), BMI, T2D, atrial fibrillation, alcohol use and smoking. For each factor, we calculated a weighted PRS for each individual based on the most recent GWAS with various GWAS p-value cutoff. We then used linear regression to estimate associations between each PRS and log transformed WMHv, controlling for age, gender and principal components of genetic ancestries. Strata-specific estimates were combined using inverse-variance weighting based meta-analysis. Results: PRS of both SBP and DBP were positively and robustly associated with WMHv in the meta-analysis (p value of the association ranging from <0.001 to 0.046 for various SNP selection strategies (GWAS p-value cutoff ranging from p<1E-5 to p<1E-8)), unlike the PRS of other risk factors, although stratum-specific significance was achieved for some factors. Conclusion: Using mendelian randomization, our results lend further evidence that high blood pressure is a causal risk factor for WMH in AIS patients. This result is consistent with previous epidemiological studies of leukoaraiosis in stroke-free populations, and it supports universal control of HTN as common contributor to WMH burden and the overall brain health.

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