Author: "Joseph F Polak" - Searchworks@Jio Institute Digital Library Search Results

415 results on '"Joseph F Polak"'

401. JENNER CENTENARY AT WARSAW

Author: Joseph F. Polak
Subjects: General Medicine
Published: 1923

402. Racial and Ethnic Differences in the Association Between Classical Cardiovascular Risk Factors and Common Carotid Intima‐Media Thickness: An Individual Participant Data Meta‐Analysis

Author: Engelbert A. Nonterah, Nigel J. Crowther, Kerstin Klipstein‐Grobusch, Abraham R. Oduro, Maryam Kavousi, Godfred Agongo, Todd J. Anderson, Gershim Asiki, Palwendé R. Boua, Solomon S. R. Choma, David J. Couper, Gunnar Engström, Jacqueline de Graaf, Jussi Kauhanen, Eva M. Lonn, Ellisiv B. Mathiesen, Lisa K. Micklesfield, Shuhei Okazaki, Joseph F. Polak, Tatjana Rundek, Jukka T. Salonen, Stephen M. Tollman, Tomi‐Pekka Tuomainen, Diederick E. Grobbee, Michéle Ramsay, and Michiel L. Bots
Subjects: atherosclerosis, cardiovascular disease risk, carotid intima‐media thickness, ethnicity, individual participant data meta‐analysis, race, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background The major risk factors for atherosclerotic cardiovascular disease differ by race or ethnicity but have largely been defined using populations of European ancestry. Despite the rising prevalence of cardiovascular disease in Africa there are few related data from African populations. Therefore, we compared the association of established cardiovascular risk factors with carotid‐intima media thickness (CIMT), a subclinical marker of atherosclerosis, between African, African American, Asian, European, and Hispanic populations. Methods and Results Cross‐sectional analyses of 34 025 men and women drawn from 15 cohorts in Africa, Asia, Europe, and North America were undertaken. Classical cardiovascular risk factors were assessed and CIMT measured using B‐mode ultrasound. Ethnic differences in the association of established cardiovascular risk factors with CIMT were determined using a 1‐stage individual participant data meta‐analysis with beta coefficients expressed as a percentage using the White population as the reference group. CIMT adjusted for risk factors was the greatest among African American populations followed by Asian, European, and Hispanic populations with African populations having the lowest mean CIMT. In all racial or ethnic groups, men had higher CIMT levels compared with women. Age, sex, body mass index, and systolic blood pressure had a significant positive association with CIMT in all races and ethnicities at varying magnitudes. When compared with European populations, the association of age, sex, and systolic blood pressure with CIMT was weaker in all races and ethnicities. Smoking (beta coefficient, 0.39; 95% CI, 0.09–0.70), body mass index (beta coefficient, 0.05; 95% CI, 0.01–0.08) and glucose (beta coefficient, 0.13; 95% CI, 0.06–0.19) had the strongest positive association with CIMT in the Asian population when compared with all other racial and ethnic groups. High‐density lipoprotein‐cholesterol had significant protective effects in African American (beta coefficient, −0.31; 95% CI, −0.42 to −0.21) and African (beta coefficient, −0.26; 95% CI, −0.31 to −0.19) populations only. Conclusions The strength of association between established cardiovascular risk factors and CIMT differed across the racial or ethnic groups and may be due to lifestyle risk factors and genetics. These differences have implications for race‐ ethnicity‐specific primary prevention strategies and also give insights into the differential contribution of risk factors to the pathogenesis of cardiovascular disease. The greatest burden of subclinical atherosclerosis in African American individuals warrants further investigations.
Published: 2022
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403. Coronary Artery Disease Events and Carotid Intima‐Media Thickness in Type 1 Diabetes in the DCCT/EDIC Cohort

Author: Joseph F. Polak, Jye‐Yu C. Backlund, Matt Budoff, Philip Raskin, Ionut Bebu, and John M. Lachin
Subjects: carotid intima‐media thickness, coronary artery disease, type 1 diabetes, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background Carotid artery intima‐media thickness (IMT) is associated with the risk of subsequent cardiovascular events in the general population. This association has not been established in type 1 diabetes. Methods and Results We studied if carotid IMT is associated with the risk of a first coronary artery disease event in participants with type 1 diabetes in the EDIC (Epidemiology of Diabetes Interventions and Complications) study, the long‐term observational follow‐up of the DCCT (Diabetes Control and Complications Trial). Between 1994 and 1996, common carotid artery and internal carotid artery IMT were measured with high‐resolution ultrasound in 1309 study participants with a mean age of 35 years and diabetes duration of 13.8 years; 52% were men. Cox proportional hazards models evaluated the association of standardized common carotid artery IMT and internal carotid artery IMT with subsequent cardiovascular events over the next 17 years. Models were adjusted for age, sex, mean hemoglobin A1c levels, and traditional cardiovascular risk factors. Associations of common carotid artery IMT with subsequent CAD were significant after adjustment for imaging device, sex, and age (hazard ratio [HR], 1.23 per 0.09 mm [95% CI, [1.04–1.45]; P=0.0141), but did not remain significant after further adjustment for traditional risk factors and hemoglobin A1c (HR, 1.14 per 0.09 mm [95% CI, 0.97–1.33]; P=0.1206). No significant associations with subsequent coronary artery disease events were seen for internal carotid artery IMT. Conclusions In the DCCT/EDIC cohort with type 1 diabetes, common carotid artery IMT, but not internal carotid artery IMT, is weakly associated with subsequent coronary artery events, an association eliminated after adjusting for coexistent traditional cardiovascular risk factors. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00360815 and NCT00360893.
Published: 2021
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404. The progression of carotid atherosclerosis and imaging markers of dementia

Author: Hediyeh Baradaran, Serkalem Demissie, Jayandra J. Himali, Alexa Beiser, Ajay Gupta, Joseph F. Polak, Charles DeCarli, Sudha Seshadri, and Jose R. Romero
Subjects: atherosclerosis, carotid artery, carotid ultrasound, hippocampus, magnetic resonance imaging, Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6
Abstract: Abstract Introduction We studied the association of carotid intima‐media thickness (CIMT) with hippocampal volume (HV) in community dwelling individuals, testing the hypothesis that persons with carotid atherosclerosis progression would have lower HV. Methods We studied 1376 Framingham Offspring participants with two carotid ultrasounds and brain magnetic resonance imaging (MRIs). We used multivariable linear regression analyses to relate CIMT progression and HV and total brain volume. Regression models were adjusted for demographics and vascular risk factors, time interval between imaging examinations, and baseline CIMT. We assessed effect modification by hypertension treatment (HRx). Results Participants with higher ICA IMT progression had significantly lower HV after adjustment for vascular risk factors and baseline IMT (standardized beta ± standard error: −0.067 ± 0.027, P = .01). We observed weaker association between ICA IMT change and HV among subjects treated for hypertension (β = −0.047, P = .19 vs β = −0.096, P = .026). Discussion Cumulative vascular risk factor exposure, reflected by CIMT progression, may increase the risk of neurodegeneration.
Published: 2020
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405. Serum Non-Esterified Fatty Acids, Carotid Artery Intima-Media Thickness and Flow-Mediated Dilation in Older Adults: The Cardiovascular Health Study (CHS)

Author: Neil K. Huang, Petra Bůžková, Nirupa R. Matthan, Luc Djoussé, Jorge R. Kizer, Kenneth J. Mukamal, Joseph F. Polak, and Alice H. Lichtenstein
Subjects: serum non-esterified fatty acid, conjugated linoleic acid, palmitoleic acid, carotid intima-media thickness, flow-mediated dilation, Cardiovascular Health Study, Nutrition. Foods and food supply, TX341-641
Abstract: Backgrounds and aims: Elevated common carotid artery intima-media thickness (carotid IMT) and diminished flow-mediated dilation (FMD) are early subclinical indicators of atherosclerosis. Serum total non-esterified fatty acid (NEFA) concentrations have been positively associated with subclinical atherosclerosis. The relations between individual NEFA, carotid IMT and FMD have as yet to be assessed. Methods: We investigated the associations between fasting serum individual NEFA, carotid IMT and FMD among Cardiovascular Health Study (CHS) participants with (n = 255 for carotid IMT, 301 for FMD) or without (n = 1314 for carotid IMT, 1462 for FMD) known atherosclerotic cardiovascular disease (ASCVD). Using archived samples (fasting) collected from 1996–1997 (baseline), 35 individual NEFAs were measured using gas chromatography. Carotid IMT and estimated plaque thickness (mean of maximum internal carotid IMT) were determined in 1998–1999. FMD was measured in 1997–1998. Linear regression adjusted by the Holm-Bonferroni method was used to assess relations between individual NEFA, carotid IMT and FMD. Results: In multivariable adjusted linear regression models per SD increment, the non-esterified trans fatty acid conjugated linoleic acid (trans-18:2 CLA) was positively associated with carotid IMT [β (95% CI): 44.8 (19.2, 70.4), p = 0.025] among participants with, but not without, ASCVD [2.16 (−6.74, 11.5), p = 1.000]. Non-esterified cis-palmitoleic acid (16:1n-7c) was positively associated with FMD [19.7 (8.34, 31.0), p = 0.024] among participants without, but not with ASCVD. No significant associations between NEFAs and estimated plaque thickness were observed. Conclusions: In older adults, serum non-esterified CLA and palmitoleic acid were positively associated with carotid IMT and FMD, respectively, suggesting potential modifiable biomarkers for arteriopathy.
Published: 2021
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406. Risk Factors for Incident Carotid Artery Revascularization among Older Adults: The Cardiovascular Health Study

Author: Parveen K. Garg, Willam J.H. Koh, Joseph A. Delaney, Ethan A. Halm, Calvin H. Hirsch, William T. Longstreth Jr., Kenneth J. Mukamal, Anna Kucharska-Newton, Joseph F. Polak, and Lesley Curtis
Subjects: Cardiovascular risk factors, Carotid duplex, Carotid endarterectomy, Carotid artery disease, Gender, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background: Population-based risk factors for carotid artery revascularization are not known. We investigated the association between demographic and clinical characteristics and incident carotid artery revascularization in a cohort of older adults. Methods: Among Cardiovascular Health Study participants, a population-based cohort of 5,888 adults aged 65 years or older enrolled in two waves (1989-1990 and 1992-1993), 5,107 participants without a prior history of carotid endarterectomy (CEA) or cerebrovascular disease had a carotid ultrasound at baseline and were included in these analyses. Cox proportional hazards multivariable analysis was used to determine independent risk factors for incident carotid artery revascularization. Results: Over a mean follow-up of 13.5 years, 141 participants underwent carotid artery revascularization, 97% were CEA. Baseline degree of stenosis and incident ischemic cerebral events occurring during follow-up were the strongest predictors of incident revascularization. After adjustment for these, factors independently associated with an increased risk of incident revascularization were: hypertension (HR 1.53; 95% CI: 1.05-2.23), peripheral arterial disease (HR 2.57; 95% CI: 1.34-4.93), and low-density lipoprotein cholesterol (HR 1.23 per standard deviation [SD] increment [35.4 mg/dL]; 95% CI: 1.04-1.46). Factors independently associated with a lower risk of incident revascularization were: female gender (HR 0.51; 95% CI: 0.34-0.77) and older age (HR 0.69 per SD increment [5.5 years]; 95% CI: 0.56-0.86). Conclusions: Even after accounting for carotid stenosis and incident cerebral ischemic events, carotid revascularization is related to age, gender, and cardiovascular risk factors. Further study of these demographic disparities and the role of risk factor control is warranted.
Published: 2016
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407. Detailed analysis of association between common single nucleotide polymorphisms and subclinical atherosclerosis: The Multi-ethnic Study of Atherosclerosis

Author: Jose D. Vargas, Ani Manichaikul, Xin-Qun Wang, Stephen S. Rich, Jerome I. Rotter, Wendy S. Post, Joseph F. Polak, Matthew J. Budoff, and David A. Bluemke
Subjects: Computer applications to medicine. Medical informatics, R858-859.7, Science (General), Q1-390
Abstract: Previously identified single nucleotide polymorphisms (SNPs) in genome wide association studies (GWAS) of cardiovascular disease (CVD) in participants of mostly European descent were tested for association with subclinical cardiovascular disease (sCVD), coronary artery calcium score (CAC) and carotid intima media thickness (CIMT) in the Multi-Ethnic Study of Atherosclerosis (MESA). The data in this data in brief article correspond to the article Common Genetic Variants and Subclinical Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis [1]. This article includes the demographic information of the participants analyzed in the article as well as graphical displays and data tables of the association of the selected SNPs with CAC and of the meta-analysis across ethnicities of the association of CIMT-c (common carotid), CIMT-I (internal carotid), CAC-d (CAC as dichotomous variable with CAC>0) and CAC-c (CAC as continuous variable, the log of the raw CAC score plus one) and CVD. The data tables corresponding to the 9p21 fine mapping experiment as well as the power calculations referenced in the article are also included. Keywords: Single nucleotide polymorphism (SNP), Common genetic variant, Subclincal atherosclerosis, Coronary artery calcium (CAC), Carotid intima-media thickness (CIMT)
Published: 2016
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408. Comparison of Carotid Plaque Score and Coronary Artery Calcium Score for Predicting Cardiovascular Disease Events: The Multi‐Ethnic Study of Atherosclerosis

Author: Adam D. Gepner, Rebekah Young, Joseph A. Delaney, Matthew J. Budoff, Joseph F. Polak, Michael J. Blaha, Wendy S. Post, Erin D. Michos, Joel Kaufman, and James H. Stein
Subjects: atherosclerosis, cardiovascular disease, carotid artery, imaging, risk factor, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: BackgroundCoronary artery calcium (CAC) predicts coronary heart disease (CHD) events better than carotid wall plaque presence; however, differences in the utility of CAC burden and carotid plaque burden across the spectrum of cardiovascular disease (CVD) events is unknown. Methods and ResultsCVD, CHD and stroke/transient ischemic attack (TIA) events were evaluated prospectively in a multiethnic cohort without CVD at baseline. Carotid plaque score was determined by the number of ultrasound‐detected plaques in the common, bifurcation, and internal carotid artery segments. CAC was detected by computed tomography. Predictive values were compared using Cox proportional hazards models, C‐statistics, and net reclassification, adjusting for traditional CVD risk factors. At baseline, the 4955 participants were mean (SD) 61.6 (10.1) years old and 52.8% female; 48.9% had CAC >0 and 50.8% had at least 1 carotid plaque. After 11.3 (3.0) years of follow‐up, 709 CVD, 498 CHD, and 262 stroke/TIA events occurred. CAC score compared to carotid plaque score was a stronger predictor of CVD (hazard ratio [HR], 1.78; 95% CI, 1.16–1.98; P
Published: 2017
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409. Carotid Intima‐Media Thickness Score, Positive Coronary Artery Calcium Score, and Incident Coronary Heart Disease: The Multi‐Ethnic Study of Atherosclerosis

Author: Joseph F. Polak, Moyses Szklo, and Daniel H. O'Leary
Subjects: atherosclerosis, cardiovascular outcomes, carotid artery, coronary artery calcification, coronary artery disease, epidemiology, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: BackgroundCommon carotid artery and internal carotid artery intima‐media thicknesses (IMT) are associated with coronary heart disease (CHD) and increase with age. Using age, sex, and race/ethnicity IMT percentiles may improve CHD prediction when added to Framingham risk factors and coronary artery calcium score. We study these possibilities in the Multi‐Ethnic Study of Atherosclerosis (MESA), a multi‐ethnic cohort of whites, Chinese, blacks, and Hispanics. Methods and ResultsIMT data were acquired in the age range 45 to 84 years. Common carotid artery and internal carotid artery IMT, sex, and race/ethnic specific normative values were calculated for each MESA participant and combined as an IMT score. Multivariable Cox‐proportional hazards models and logistic regression models were generated with CHD as outcome adding the IMT score to (1) a base model with Framingham risk factors, sex, race/ethnicity and (2) the base model with coronary artery calcium added. Harrell's C‐statistics and area under the curve were estimated. Median follow‐up was 10.2 years (interquartile range: 9.7, 10.7 years) with 429 first‐time CHD events. Mean age was 62.1 years and 52.6% of participants were women. IMT score increased the base area under the curve from 0.7210 to 0.7396 (P=0.0008) and with positive coronary artery calcium score added to the model, from 0.7627 to 0.7714 (P=0.02). ConclusionsA carotid IMT score based on normative data incrementally adds to Framingham risk factors and a positive calcium score in predicting first‐time CHD in an ethnically diverse cohort.
Published: 2017
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410. Concentration of Smaller High‐Density Lipoprotein Particle (HDL‐P) Is Inversely Correlated With Carotid Intima Media Thickening After Confounder Adjustment: The Multi Ethnic Study of Atherosclerosis (MESA)

Author: Daniel Seung Kim, Yatong K. Li, Griffith A. Bell, Amber A. Burt, Tomas Vaisar, Patrick M. Hutchins, Clement E. Furlong, James D. Otvos, Joseph F. Polak, Martinson Kweku Arnan, Joel D. Kaufman, Robyn L. McClelland, W. T. Longstreth, and Gail P. Jarvik
Subjects: antioxidant, carotid intima media thickening, cerebrovascular disease, high‐density lipoprotein cholesterol, high‐density lipoprotein particle concentration, paraoxonase 1, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: BackgroundRecent studies have failed to establish a causal relationship between high‐density lipoprotein cholesterol levels (HDL‐C) and cardiovascular disease (CVD), shifting focus to other HDL measures. We previously reported that smaller/denser HDL levels are protective against cerebrovascular disease. This study sought to determine which of small+medium HDL particle concentration (HDL‐P) or large HDL‐P was more strongly associated with carotid intima‐media thickening (cIMT) in an ethnically diverse cohort. Methods and ResultsIn cross‐sectional analyses of participants from the Multi Ethnic Study of Atherosclerosis (MESA), we evaluated the associations of nuclear magnetic resonance spectroscopy–measured small+medium versus large HDL‐P with cIMT measured in the common and internal carotid arteries, through linear regression. After adjustment for CVD confounders, low‐density lipoprotein cholesterol (LDL‐C), HDL‐C, and small+medium HDL‐P remained significantly and inversely associated with common (coefficient=−1.46 μm; P=0.00037; n=6512) and internal cIMT (coefficient=−3.82 μm; P=0.0051; n=6418) after Bonferroni correction for 4 independent tests (threshold for significance=0.0125; α=0.05/4). Large HDL‐P was significantly and inversely associated with both cIMT outcomes before HDL‐C adjustment; however, after adjustment for HDL‐C, the association of large HDL‐P with both common (coefficient=1.55 μm; P=0.30; n=6512) and internal cIMT (coefficient=4.84 μm; P=0.33; n=6418) was attenuated. In a separate sample of 126 men, small/medium HDL‐P was more strongly correlated with paraoxonase 1 activity (rp=0.32; P=0.00023) as compared to both total HDL‐P (rp=0.27; P=0.0024) and large HDL‐P (rp=0.02; P=0.41) measures. ConclusionsSmall+medium HDL‐P is significantly and inversely correlated with cIMT measurements. Correlation of small+medium HDL‐P with cardioprotective paraoxonase 1 activity may reflect a functional aspect of HDL responsible for this finding.
Published: 2016
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411. Carotid Intima‐Media Thickness and Arterial Stiffness and the Risk of Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study, Multi‐Ethnic Study of Atherosclerosis (MESA), and the Rotterdam Study

Author: Lin Y. Chen, Maarten J. G. Leening, Faye L. Norby, Nicholas S. Roetker, Albert Hofman, Oscar H. Franco, Wei Pan, Joseph F. Polak, Jacqueline C.M. Witteman, Richard A. Kronmal, Aaron R. Folsom, Saman Nazarian, Bruno H. Stricker, Susan R. Heckbert, and Alvaro Alonso
Subjects: arterial stiffness, atherosclerosis, atrial fibrillation, carotid intima‐media thickness, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: BackgroundWe evaluated the association of carotid intima‐media thickness (cIMT), carotid plaque, carotid distensibility coefficient (DC), and aortic pulse wave velocity (PWV) with incident atrial fibrillation (AF) and their role in improving AF risk prediction beyond the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)‐AF risk score. Methods and ResultsWe analyzed data from 3 population‐based cohort studies: Atherosclerosis Risk in Communities (ARIC) Study (n=13 907); Multi‐Ethnic Study of Atherosclerosis (MESA; n=6640), and the Rotterdam Study (RS; n=5220). We evaluated the association of arterial indices with incident AF and computed the C‐statistic, category‐based net reclassification improvement (NRI), and relative integrated discrimination improvement (IDI) of incorporating arterial indices into the CHARGE‐AF risk score (age, race, height weight, systolic and diastolic blood pressure, antihypertensive medication use, smoking, diabetes, previous myocardial infarction, and previous heart failure). Higher cIMT (meta‐analyzed hazard ratio [95% CI] per 1‐SD increment, 1.12 [1.08–1.16]) and presence of carotid plaque (1.30 [1.19–1.42]) were associated with higher AF incidence after adjustment for CHARGE‐AF risk‐score variables. Lower DC and higher PWV were associated with higher AF incidence only after adjustment for the CHARGE‐AF risk‐score variables excepting height, weight, and systolic and diastolic blood pressure. Addition of cIMT or carotid plaque marginally improved CHARGE‐AF score prediction as assessed by the relative IDI (estimates, 0.025–0.051), but not when assessed with the C‐statistic and NRI. ConclusionsHigher cIMT, presence of carotid plaque, and greater arterial stiffness are associated with higher AF incidence, indicating that atherosclerosis and arterial stiffness play a role in AF etiopathogenesis. However, arterial indices only modestly improve AF risk prediction.
Published: 2016
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412. Carotid Atherosclerosis and Cerebral Microbleeds: The Framingham Heart Study

Author: José R. Romero, Sarah R. Preis, Alexa Beiser, Charles DeCarli, Ralph B. D'Agostino, Philip A. Wolf, Ramachandran S. Vasan, Joseph F. Polak, and Sudha Seshadri
Subjects: brain magnetic resonance imaging, carotid atherosclerosis, carotid intima–media thickness, cerebral microbleeds, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: BackgroundCarotid atherosclerosis is associated with subclinical ischemic cerebrovascular disease, but its role in hemorrhage‐prone small vessel disease—represented by cerebral microbleed (CMB)—is unclear, although vascular risk factors underlie both conditions. We hypothesized that persons with carotid atherosclerosis would have higher risk of CMB, particularly in deep regions. Methods and ResultsWe studied 1243 participants in the Framingham Offspring Study (aged 56.9±8.8 years; 53% women) with carotid ultrasound available on 2 occasions (1995–1998 and 2005–2008) prior to brain magnetic resonance imaging. Using multivariable logistic regression, we related baseline carotid stenosis, baseline intima–media thickness, and site‐specific carotid intima–media thickness progression (at internal and common carotid locations) to the prevalence and location (lobar or deep plus mixed) of CMB. In addition, we assessed effect modification by lipid levels and use of statin and antithrombotic medications. Carotid stenosis ≥25% (a marker of cerebrovascular atherosclerosis) was associated with presence of CMB overall (Odds Ratio 2.20, 95% CI 1.10–4.40) and at deep and mixed locations (odds ratio 3.60, 95% CI 1.23–10.5). Baseline carotid intima–media thickness was not associated with CMB. Progression of common carotid artery intima–media thickness among persons on hypertension treatment was associated with lower risk of deep and mixed CMB (odds ratio per SD 0.41, 95% CI 0.18–0.96). ConclusionsCumulative vascular risk factor exposure may increase the risk of CMB, especially in deep regions. The apparent paradoxical association of carotid intima–media thickness progression with lower risk of CMB may reflect benefits of intensive vascular risk factor treatment among persons with higher cardiovascular risk and deserves further investigation. If replicated, the results may have potential implications for assessment of preventive and therapeutic interventions for subclinical cerebral hemorrhage.
Published: 2016
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413. Variants at the APOA5 locus, association with carotid atherosclerosis, and modification by obesity: the Framingham Study

Author: Roberto Elosua, Jose M. Ordovas, L. Adrienne Cupples, Chao-Qiang Lai, Serkalem Demissie, Caroline S. Fox, Joseph F. Polak, Philip A. Wolf, Ralph B. D'Agostino, Sr., and Christopher J. O'Donnell
Subjects: apolipoproteins, carotid arteries, epidemiology, genetics, apolipoprotein A5 gene, Biochemistry, QD415-436
Abstract: Genetic variation at the apolipoprotein A5 gene (APOA5) is associated with increased triglyceride concentrations, a risk factor for atherosclerosis. Carotid intimal medial thickness (IMT) is a surrogate measure of atherosclerosis burden. We sought to determine the association of common APOA5 genetic variants with carotid IMT and stenosis. A total of 2,273 Framingham Offspring Study participants underwent carotid ultrasound and had data on at least one of the five APOA5 variants (−1131T>C, −3A>G, 56C>G, IVS3+476G >A, and 1259T>C). Although none of the individual variants was significantly associated with carotid measures, the haplotype defined by the presence of the rare allele of the 56C>G variant was associated with a higher common carotid artery (CCA) IMT compared with the wild-type haplotype (0.75 vs. 0.73 mm; P < 0.05). The rare allele of each of the −1131T >C, −3A>G, IVS3+476G>A, and 1259T>C variants and the haplotype defined by the presence of the rare alleles in these four variants were each significantly associated with CCA IMT in obese participants. These associations remained significant even after adjustment for triglycerides. APOA5 variants were associated with CCA IMT, particularly in obese participants. The mechanism of these associations and the effect modification by obesity are independent of fasting triglyceride levels.
Published: 2006
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414. Association of APOE genotype with carotid atherosclerosis in men and women

Author: Roberto Elosua, Jose M. Ordovas, L. Adrienne Cupples, Caroline S. Fox, Joseph F. Polak, Philip A. Wolf, Ralph A. D’Agostino, Sr., and Christopher J. O’Donnell
Subjects: genetics, atherosclerosis, carotid artery, lipoprotein, apolipoprotein E genotype, Biochemistry, QD415-436
Abstract: The aim of this study was to determine the association between APOE genotype and carotid atherosclerosis, defined as intimal-medial thickness (IMT) and stenosis, and to assess if other cardiovascular risk factors modify this association. A total of 1,315 men and 1,408 women from the Framingham Offspring Study underwent carotid ultrasound during examination cycle 6 and had complete data on APOE genotype. Three APOE genotype groups were defined: APOE2 (including E2/E2, E3/E2 genotypes), APOE3 (E3/E3), and APOE4 (including E4/E3, E4/E4 genotypes). Carotid IMT and the presence of carotid stenosis > 25% were determined by ultrasonography. In women, the APOE2 group was associated with lower carotid IMT (0.67 vs. 0.73 mm) and lower prevalence of stenosis (odds ratio = 0.49; 95% confidence interval = 0.30–0.81) compared with the APOE3 group. In men, APOE genotype was not associated with carotid IMT or stenosis in the whole group; however, diabetes modified the association between APOE genotype and carotid IMT (P for interaction = 0.044). Among men with diabetes, the APOE4 group was associated with a higher internal carotid artery IMT (1.22 mm) than the APOE3 group (0.90 mm) or the APOE2 group (0.84 mm).The E2 allele was associated with lower carotid atherosclerosis in women, and the E4 allele was associated with higher internal carotid IMT in diabetic men.
Published: 2004
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415. Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting

Author: Chauhan, Ganesh, Adams, Hieab H H, Jian, Xueqiu, Sharma, Pankaj, Sudlow, Cathie L M, Rosand, Jonathan, Woo, Daniel, Cole, John W, Meschia, James F, Slowik, Agnieszka, Thijs, Vincent, Lindgren, Arne, Melander, Olle, Malik, Rainer, Grewal, Raji P, Rundek, Tatjana, Rexrode, Kathy, Rothwell, Peter M, Arnett, Donna K, Jern, Christina, Johnson, Julie A, Benavente, Oscar R, Wasssertheil-Smoller, Sylvia, Lee, Jin-Moo, Traylor, Matthew, Wong, Quenna, Mitchell, Braxton D, Rich, Stephen S, McArdle, Patrick F, Geerlings, Mirjam I, van der Graaf, Yolanda, de Bakker, Paul I W, Asselbergs, Folkert W, Srikanth, Velandai, Thomson, Russell, Pulit, Sara L, McWhirter, Rebekah, Moran, Chris, Callisaya, Michele, Phan, Thanh, Rutten-Jacobs, Loes C A, Bevan, Steve, Tzourio, Christophe, Mather, Karen A, Sachdev, Perminder S, van Duijn, Cornelia M, Amouyel, Philippe, Worrall, Bradford B, Dichgans, Martin, Kittner, Steven J, Markus, Hugh S, Ikram, Mohammad A, Fornage, Myriam, Launer, Lenore J, Seshadri, Sudha, Longstreth, W. T., Debette, Stéphanie, Mazoyer, Bernard, Network, Stroke Genetics, Almgren, Peter, Anderson, Christopher D, Attia, John, Ay, Hakan, Brown, Robert D, Bustamante, Mariana, Zhu, Yi-Cheng, Cheng, Yu-Ching, Cotlarciuc, Ioana, Cruchaga, Carlos, de Bakker, Paul Iw, Delavaran, Hossein, Engström, Gunnar, Kaffashian, Sara, Heitsch, Laura, Holliday, Elizabeth, Ibanez, Laure, Ilinca, Andreea, Irvin, Marguerite R, Jackson, Rebecca D, Jimenez-Conde, Jordi, Jood, Katarina, Schilling, Sabrina, Kissela, Brett M, Kleindorfer, Dawn O, Labovitz, Daniel, Laurie, Cathy C, Lemmens, Robin, Levi, Christopher, Li, Linxin, Lindgren, Arne G, Beecham, Gary W, Maguire, Jane, Müller-Nurasyid, Martina, Norrving, Bo, Peddareddygari, Leema Reddy, Pera, Joanna, Satizabal, Claudia L, Montine, Thomas J, Rexrode, Kathryn, Ribasés, Marta, Roquer, Jaume, Rost, Natalia S, Sacco, Ralph L, Schmidt, Reinhold, Schellenberg, Gerard D, Soriano-Tárraga, Carolina, Stanne, Tara, Stauch, Konstantin, Stine, O. C., Sudlow, Cathie Lm, Thijs, Vincent N S, Weir, David, Williams, Stephen R, Kjartansson, Olafur, Xu, Huichun, Hyacinth, Hyacinth I, Marini, Sandro, Nyquist, Paul, Lewis, Cathryn, Hansen, Bjorn, Guðnason, Vilmundur, Biffi, Alessandro, Kourkoulis, Christina, Anderson, Chris, Giese, Anne-Katrin, Sacco, Ralph, Chung, Jong-Won, Kim, Gyeong-Moon, Knopman, David S, Lubitz, Steven, Bourcier, Romain, Howson, Joanna, Granata, Alessandra, Drazyk, Anna, Markus, Hugh, Wardlaw, Joanna, Mitchell, Braxton, Cole, John, Hopewell, Jemma, Griswold, Michael E, Walters, Robin, Turnbull, Iain, Worrall, Bradford, Bis, Josh, Reiner, Alex, Dhar, Raj, Prasad, Kameshwar, Sarnowski, Chloé, Windham, B Gwen, Aparicio, Hugo Javier, Yang, Qiong, Chasman, Daniel, Phuah, Chia-Ling, Liu, Guiyou, Elkind, Mitchell, Lange, Leslie, Rost, Natalia, James, Michael, Gottesman, Rebecca F, Stewart, Jill, Vojinovic, Dina, Parati, Eugenio, Boncoraglio, Giorgio, Zand, Ramin, Bijlenga, Philippe, Selim, Magdy, Grond-Ginsbach, Caspar, Strbian, Daniel, Mosley, Thomas H, Tomppo, Liisa, Sallinen, Hanne, Pfeiffer, Dorothea, Torres, Nuria, Barboza, Miguel, Laarman, Melanie, Carriero, Roberta, Soriano, Carolina, Gill, Dipender, Debette, Stephanie, Mishra, Aniket, Wu, Jer-Yuarn, Ko, Tai-Ming, Bione, Silvia, Tatlisumak, Turgut, Holmegaard, Lukas, Yue, Suo, Bis, Joshua C, Saba, Yasaman, Bersano, Anna, Schlicht, Kristina, Ninomiya, Toshiharu, Oberstein, Saskia Lesnik, Lee, Tsong-Hai, Schmidt, Helena, Wasselius, Johan, Drake, Mattias, Stenman, Martin, Crawford, Katherine, Lena, Umme, Mateen, Farrah, Takeuchi, Fumihiko, Wu, Ona, Schirmer, Markus, Cramer, Steve, Golland, Polina, Brown, Robert, Meschia, James, Ross, Owen A, Pare, Guillaume, Chong, Mike, Yamaguchi, Shuhei, Gwinn, Katrina, Chen, Christopher, Koenig, Jim, Giralt, Eva, Saleheen, Danish, de Leeuw, Frank-Erik, Klijn, Karin, Kamatani, Yoichiro, Kubo, Michiaki, Nabika, Toru, Okada, Yukinori, Pedersen, Annie, Olsson, Maja, Martín, Juan José, Tan, Eng King, Frid, Petrea, Lee, Chaeyoung, Tregouet, David, Leung, Thomas, Kato, Norihiro, Choy, Richard, Loo, Keat Wei, Rinkel, Gabriel, Franca, Paulo, Cendes, Iscia, Carrera, Caty, Fernandez-Cadenas, Israel, Montaner, Joan, Kim, Helen, Rajan, Kumar B, Owolabi, Mayowa, Sofat, Reecha, Bakker, Mark, Ruigrok, Ynte, Hauer, Allard, van der Laan, Sander W, Irvin, Ryan, Sargurupremraj, Murali, Pezzini, Alessandro, Aggarwal, Neelum T, Abd-Allah, Foad, Liebeskind, David, Tan, Rhea, Danesh, John, Donatti, Amanda, Avelar, Wagner, Broderick, Joseph, Sudlow, Cathie, De Jager, Philip L, Rannikmae, Kristiina, McDonough, Caitrin Wheeler, van Agtmael, Tom, Walters, Matthew, Söderholm, Martin, Lorentzen, Erik, Olsson, Sandra, Olsson, Martina, Akinyemi, Rufus, Evans, Denis A, Cotlatciuc, Ioana, McArdle, Patrick, Dave, Tushar, Kittner, Steven, Faber, James E, Millwood, Iona, Márquez, Elsa Valdés, Mancuso, Michelangelo, Vibo, Riina, Teumer, Alexander, Psaty, Bruce M, Korv, Janika, Majersik, Jennifer, DeHavenon, Adam, Alexander, Matthew, Sale, Michele, Southerland, Andrew, Owens, Debra, Psaty, Bruce, Rotter, Jerome I, Wolfe, Stacey Quintero, Langefeld, Carl, Konrad, Jan, Sheth, Kevin, Falcone, Guido, Donahue, Kathleen, Simpkins, Alexis N, Liang Byorn, Tan Wei, Rice, Kenneth, Chan, Bernard, Clatworthy, Phil, Florez, Jose, Harshfield, Eric, Hozawa, Atsushi, Hsu, Chung, Hu, Chaur-Jong, Ihara, Masafumi, Lange, Marcos, Lopez, Oscar L, Lee, Soo Ji, Lee, I-Hui, Musolino, Patricia, Nakatomi, Hirofumi, Park, Kwang-Yeol, Riley, Chris, Sung, Joohon, Suzuki, Hideaki, Vo, Katie, Liao, Jiemin, Washida, Kazuo, Ibenez, Laura Garcia, Hofman, Albert, Algra, Ale, Reiner, Alex P, Doney, Alexander S F, Gschwendtner, Andreas, Vicente, Astrid M, Nordestgaard, Børge G, Carty, Cara L, Cheng, Ching-Yu, Palmer, Colin N A, Gamble, Dale M, Ringelstein, E Bernd, Valdimarsson, Einar, Davies, Gail, Wong, Tien Y, Pasterkamp, Gerard, Kuhlenbäumer, Gregor, Thorleifsson, Gudmar, Falcone, Guido J, Pare, Guillame, Ikram, Mohammad K, Aparicio, Hugo J, Deary, Ian, Hopewell, Jemma C, Liu, Jingmin, van der Lee, Sven J, Attia, John R, Ferro, Jose M, Bis, Joshua, Furie, Karen, Stefansson, Kari, Berger, Klaus, Kostulas, Konstantinos, Rannikmae, Kristina, Ikram, M Arfan, Sargurupremraj, Muralidharan, Amin, Najaf, Benn, Marianne, Farrall, Martin, Pandolfo, Massimo, Nalls, Mike, van Zuydam, Natalie R, Chouraki, Vincent, Abrantes, Patricia, Higgins, Peter, Lichtner, Peter, DeStefano, Anita L, Clarke, Robert, Abboud, Sherine, Oliveira, Sofia A, Gretarsdottir, Solveig, Mosley, Thomas, Battey, Thomas Wk, Thorsteinsdottir, Unnur, Thijs, Vincent Ns, Zhao, Wei, Chen, Wei-Min, Romero, Jose R, Albert, Marilyn S, Albin, Roger L, Apostolova, Liana G, Arnold, Steven E, Asthana, Sanjay, Atwood, Craig S, Baldwin, Clinton T, Barmada, M Michael, Barnes, Lisa L, Maillard, Pauline, Barral, Sandra, Beach, Thomas G, Becker, James T, Beekly, Duane, Bennett, David A, Bigio, Eileen H, Bird, Thomas D, Blacker, Deborah, Boeve, Bradley F, DeCarli, Charles, Boxer, Adam, Burke, James R, Burns, Jeffrey M, Buxbaum, Joseph D, Byrd, Goldie S, Cai, Guiqing, Cairns, Nigel J, Cantwell, Laura B, Cao, Chuanhai, Carlsson, Cynthia M, Wardlaw, Joanna M, Carney, Regina M, Carrasquillo, Minerva M, Carroll, Steven L, Chui, Helena C, Clark, David G, Cribbs, David H, Crocco, Elizabeth A, Hernández, Maria Del C Valdés, Demirci, F Yesim, Dick, Malcolm, Dickson, Dennis W, Duara, Ranjan, Ertekin-Taner, Nilufer, Faber, Kelley M, Fallin, M Daniele, Fallon, Kenneth B, Fardo, David W, Luciano, Michelle, Farlow, Martin R, Farrer, Lindsay A, Ferris, Steven, Foroud, Tatiana M, Frosch, Matthew P, Galasko, Douglas R, Gearing, Marla, Geschwind, Daniel H, Ghetti, Bernardino, Gilbert, John R, Hofer, Edith, Liewald, David, Go, Rodney C P, Goate, Alison M, Graff-Radford, Neill R, Green, Robert C, Griffith, Patrick, Growdon, John H, Haines, Jonathan L, Hakonarson, Hakon, Hamilton, Ronald L, Hamilton-Nelson, Kara L, Deary, Ian J, Haroutunian, Vahram, Harrell, Lindy E, Honig, Lawrence S, Huebinger, Ryan M, Hulette, Christine M, Hyman, Bradley T, Jicha, Gregory A, Jin, Lee-Way, Jun, Gyungah, Kamboh, M Ilyas, Starr, John M, Karydas, Anna, Kauwe, John S K, Kaye, Jeffrey A, Kim, Ronald, Kowall, Neil W, Kramer, Joel H, Kukull, Walter A, Kunkle, Brian W, LaFerla, Frank M, Lah, James J, Bastin, Mark E, Lang-Walker, Rosalyn, Larson, Eric B, Leverenz, James B, Levey, Allan I, Li, Ge, Lieberman, Andrew P, Logue, Mark W, Lunetta, Kathryn L, Lyketsos, Constantine G, Muñoz Maniega, Susana, Mack, Wendy J, Manly, Jennifer J, Marson, Daniel C, Martin, Eden R, Martiniuk, Frank, Mash, Deborah C, Masliah, Eliezer, Mayeux, Richard, McKee, Ann C, Mesulam, Marsel, Slagboom, P Eline, Miller, Bruce L, Miller, Carol A, Miller, Joshua W, Morris, John C, Murrell, Jill R, Naj, Adam C, Obisesan, Thomas O, Olichney, John M, Pankratz, Vernon S, Beekman, Marian, Parisi, Joseph E, Partch, Amanda, Paulson, Henry L, Pericak-Vance, Margaret A, Perry, William, Peskind, Elaine, Petersen, Ronald C, Pierce, Aimee, Poon, Wayne W, Potter, Huntington, Deelen, Joris, Quinn, Joseph F, Raj, Ashok, Raj, Towfique, Raskind, Murray, Reiman, Eric M, Reisberg, Barry, Reitz, Christiane, Ringman, John M, Roberson, Erik D, Rosen, Howard J, Uh, Hae-Won, Rosenberg, Roger N, Sager, Mark A, Sano, Mary, Saykin, Andrew J, Schneider, Julie A, Schneider, Lon S, Seeley, William W, Smith, Amanda G, Sonnen, Joshua A, Spina, Salvatore, Stern, Robert A, Swerdlow, Russell H, Tanzi, Rudolph E, Thornton-Wells, Tricia A, Trojanowski, John Q, Troncoso, Juan C, Tsuang, Debby W, Valladares, Otto, Van Deerlin, Vivianna M, Trompet, Stella, Brodaty, Henry, Van Eldik, Linda J, Vardarajan, Badri N, Vinters, Harry V, Vonsattel, Jean Paul, Wang, Li-San, Weintraub, Sandra, Welsh-Bohmer, Kathleen A, Williamson, Jennifer, Wingo, Thomas S, Wishnek, Sarah, Wright, Margaret J, Woltjer, Randall L, Wright, Clinton B, Younkin, Steven G, Yu, Chang-En, Yu, Lei, Chu, Audrey Y, Havulinna, Aki S, Ames, David, Smith, Albert Vernon, Choi, Seung Hoan, Garcia, Melissa E, Manichaikul, Ani, Gustafsson, Stefan, Bartz, Traci M, Boncoraglio, Giorgio B, Bellenguez, Céline, Vidal, Jean Sebastien, Wiggins, Kerri L, Xue, Flora, Ripatti, Samuli, Liu, Yongmei, Hoed, Marcel den, Heckbert, Susan R, Smith, Nicholas L, Buring, Julie E, Ridker, Paul M, Berr, Claudine, Dartigues, Jean-François, Beecham, Ashley H, Hamsten, Anders, Magnusson, Patrik K, Pedersen, Nancy L, Lannfelt, Lars, Lind, Lars, Lindgren, Cecilia M, Morris, Andrew P, Koudstaal, Peter J, Portegies, Marileen Lp, Blanton, Susan H, Uitterlinden, André G, de Craen, Anton Jm, Ford, Ian, Jukema, J Wouter, Stott, David J, Allen, Norrina B, Sale, Michele M, Johnson, Andrew D, White, Charles C, Paulista Markus, Marcello Ricardo, Nalls, Michael A, Beiser, Alexa, Vartiainen, Erkki, French, Curtis R, Kurth, Tobias, Harris, Tamara B, deStefano, Anita L, Schmidt, Carsten Oliver, Salomaa, Veikko, Wen, Wei, Ingelsson, Erik, Chasman, Daniel I, Verhaaren, Benjamin F J, Hilal, Saima, Thalamuthu, Anbupalam, Smith, Jennifer A, Ikram, M Kamran, Adams, Hieab H, Lopez, Lorna M, van Buchem, Mark A, Armstrong, Nicola J, van der Grond, Jeroen, Smith, Albert V, Hegenscheid, Katrin, de Andrade, Mariza, Atkinson, Elizabeth J, Beiser, Alexa S, Boerwinkle, Eric, Chong, Elizabeth, Brickman, Adam M, Bryan, R Nick, Chen, Christopher P L H, de Craen, Anton J M, Crivello, Fabrice, Schofield, Peter R, Dufouil, Carole, Elkind, Mitchell S V, Freudenberger, Paul, Habes, Mohamad, Heiss, Gerardo, Kwok, John B, Ibrahim-Verbaas, Carla A, Lewis, Cora E, Liewald, David C M, van der Lugt, Aad, Martinez, Oliver O, Nauck, Matthias, Niessen, Wiro J, Oostra, Ben A, Rice, Kenneth M, von Sarnowski, Bettina, Schreiner, Pamela J, Schuur, Maaike, Sidney, Stephen S, Sigurdsson, Sigurdur, Stott, David J M, van Swieten, John C, Töglhofer, Anna Maria, Turner, Stephen T, Vernooij, Meike W, Wang, Jing J, Wolf, Christiane, Zijdenbos, Alex, Kardia, Sharon L R, DeCarli, Charles C, Seshadri, Sudha S, Kavousi, Maryam, Franceschini, Nora, Isaacs, Aaron, Abecasis, Gonçalo R, Schminke, Ulf, Post, Wendy, Cupples, L Adrienne, Huffman, Jennifer E, Lehtimäki, Terho, Baumert, Jens, Münzel, Thomas, Dehghan, Abbas, North, Kari, Oostra, Ben, Stoegerer, Eva-Maria, Hayward, Caroline, Raitakari, Olli, Meisinger, Christa, Schillert, Arne, Sanna, Serena, Völzke, Henry, Thorsson, Bolli, Fox, Caroline S, Wittfeld, Katharina, Rivadeneira, Fernando, Nambi, Vijay, Halperin, Eran, Petrovic, Katja E, Peltonen, Leena, Wichmann, H Erich, Schnabel, Renate B, Dörr, Marcus, Parsa, Afshin, Aspelund, Thor, Grabe, Hans J, Demissie, Serkalem, Kathiresan, Sekar, Reilly, Muredach P, Taylor, Kent, Uitterlinden, Andre, Couper, David J, Sitzer, Matthias, Kähönen, Mika, Illig, Thomas, Wild, Philipp S, Hosten, Norbert, Orru, Marco, Lüdemann, Jan, Shuldiner, Alan R, Eiriksdottir, Gudny, Seissler, Jochen, Zeller, Tanja, Usala, Gianluca, Ernst, Florian, D'Agostino, Ralph B, O'Leary, Daniel H, Ballantyne, Christie, Thiery, Joachim, Ziegler, Andreas, Lakatta, Edward G, Chilukoti, Ravi Kumar, Völker, Uwe, Wolf, Philip A, Polak, Joseph F, Li, Xia, Rathmann, Wolfgang, Uda, Manuela, Klopp, Norman, Wilson, James F, Viikari, Jorma, Koenig, Wolfgang, Blankenberg, Stefan, Newman, Anne B, Witteman, Jacqueline, van Duijn, Cornelia, Scuteri, Angelo, Homuth, Georg, Gudnason, Vilmundur, O'Donnell, Christopher J, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lund University [Lund], Stroke Genetics Network (SiGN), METASTROKE, Alzheimer’s Disease Genetics Consortium (ADGC), Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, Peter Almgren, MSC, Christopher D. Anderson, MD, Donna K. Arnett, PhD, MSPH, John Attia, MD, PhD, FRACP, FRCPC, Hakan Ay, MD, Oscar R. Benavente, MD, Steve Bevan, PhD, Robert D. Brown, MD, Mariana Bustamante, PhD, Yu-Ching Cheng, PhD, John W. Cole, MD, MS, Ioana Cotlarciuc, PhD, Carlos Cruchaga, PhD, Paul IW. de Bakker, PhD, Hossein Delavaran, MD, PhD, Martin Dichgans, MD, Gunnar Engström, MD, PHD, PROF, Myriam Fornage, PhD, Raji P. Grewal, MD, Laura Heitsch, MD, Elizabeth Holliday, MSc, PhD, Laure Ibanez, PhD, Andreea Ilinca, MD, Marguerite R. Irvin, PhD, Rebecca D. Jackson, MD, Christina Jern, MD, PhD, Jordi Jimenez-Conde, MD, PhD, Julie A. Johnson, PharmD, Katarina Jood, MD, PhD, Brett M. Kissela, MD, MS, Steven J. Kittner, MD, Dawn O. Kleindorfer, MD, MS, Daniel Labovitz, MD, Cathy C. Laurie, PhD, Jin-Moo Lee, MD, PhD, Robin Lemmens, MD PhD, Christopher Levi, MBBS B Med Sci FRACP, Linxin Li, DPhil, Arne G. Lindgren, MD, PhD, Jane Maguire, PhD, Hugh S. Markus, FRCP, Patrick F. McArdle, PhD, Olle Melander, MD, PHD, PROF, James F. Meschia, MD, Braxton D. Mitchell, PhD, Martina Müller-Nurasyid, PhD, Bo Norrving, MD, PhD, Leema Reddy Peddareddygari, MD, Joanna Pera, MD, PhD, Sara L. Pulit, PhD, Kathryn Rexrode, MD, MPH, Marta Ribasés, PhD, BSc, Jaume Roquer, MD, PhD, Natalia S. Rost, MD, Peter M. Rothwell, FMedSci, Tatjana Rundek, MD PhD, Ralph L. Sacco, MD MS, Reinhold Schmidt, MD, Pankaj Sharma, MD PhD, Agnieszka Slowik, MD, PhD, Carolina Soriano-Tárraga, BSc, PhD, Tara Stanne, PhD, Konstantin Stauch, PhD, O C. Stine, PhD, Cathie LM. Sudlow, BMBCh, MSc, DPhil, FRCP (Ed), Vincent N.S. Thijs, MD, PhD, Sylvia Wasssertheil-Smoller, PhD, David Weir, PhD, Stephen R. Williams, PhD, Quenna Wong, PhD, Daniel Woo, MD, MS, Bradford B. Worrall, MD, MSc, Huichun Xu, MD, PhD, Sudha Seshadri, MD, Hyacinth I Hyacinth, MD, Sandro Marini, MD, Paul Nyquist, MD, PhD, Cathryn Lewis, PhD, Bjorn Hansen, MD, Bo Norrving, MD, PhD, Jonathan Rosand, MD, Alessandro Biffi, MD, Christina Kourkoulis, Bachelor, Chris Anderson, MD, MMSc, Anne-Katrin Giese, MD, Ralph Sacco, MD, MS, Pankaj Sharma, MD, PhD, Jong-Won Chung, MD, MSc, Gyeong-Moon Kim, MD, Steven Lubitz, MD, MPH, Romain Bourcier, MD, Joanna Howson, PhD, Alessandra Granata, PhD, Anna Drazyk, MRCPI, Hugh Markus, MD, Joanna Wardlaw, MD, Braxton Mitchell, MPH, PHD, John Cole, MD, MS, Jemma Hopewell, PhD, FESC, Robin Walters, MA, PhD, PgDip, Iain Turnbull, BA(Hons) MB BChir MRCP(UK) MRCGP, Bradford Worrall, MD, MSc, Josh Bis, PhD, Alex Reiner, MD, MSc, Raj Dhar, MD, Laura Heitsch, MD, Jin-Moo Lee, MD, PhD, Kameshwar Prasad, MD, DM, MMSc, FRCP(Edin), FAMS, Chloé Sarnowski, PhD, Hugo Javier Aparicio, MD, Qiong Yang, PhD, Daniel Chasman, PhD, Kathryn Rexrode, MD, MPH, Chia-Ling Phuah, MD, Guiyou Liu, PhD, Mitchell Elkind, MD, MSc, Leslie Lange, PhD, Natalia Rost, MD, Michael James, MD, Jill Stewart, PhD, Dina Vojinovic, MD, MS, Vincent Thijs, MD, PhD, Eugenio Parati, MD, Giorgio Boncoraglio, MD, Ramin Zand, MD, Philippe Bijlenga, MD, PhD, Magdy Selim, MD, PhD, Caspar Grond-Ginsbach, PhD, Daniel Strbian, MD, PhD, Liisa Tomppo, MD, Hanne Sallinen, MD, Dorothea Pfeiffer, MD, Nuria Torres, MSc, Miguel Barboza, MD, Melanie Laarman, PhD candidate, Roberta Carriero, PhD, Elizabeth Holliday, PhD, Jordi Jimenez-Conde, MD, PhD, Carolina Soriano, BSc, PhD, Dipender Gill, PhD, Stephanie Debette, MD, PhD, Aniket Mishra, PhD, Jer-Yuarn Wu, PhD, Tai-Ming Ko, PhD, Silvia Bione, PhD, Katarina Jood, MD, PhD, Turgut Tatlisumak, MD, PhD, Lukas Holmegaard, PhD, Suo Yue, system engineer, Anna bersano, MD, PhD, Joanna Pera, MD, PhD, Agnieszka Slowik, MD, PhD, Christopher Levi, MBBS B Med Sci FRACP, Kristina Schlicht, Dipl. Biol., Robin Lemmens, MD, PhD, Toshiharu Ninomiya, MD, PhD, Saskia Lesnik Oberstein, PhD, Tsong-Hai Lee, MD, PhD, Rainer Malik, PhD, Martin Dichgans, MD, Arne Lindgren, MD, PhD, Johan Wasselius, MD, PhD, Mattias Drake, student, Olle Melander, MD, PHD, Martin Stenman, MD, Andreea Ilinca, MD, Katherine Crawford, BS, Umme Lena, Bachelors of Arts, Farrah Mateen, MD, PhD, Hakan Ay, MD, Ona Wu, PhD, Markus Schirmer, PhD, Steve Cramer, MD, Polina Golland, PhD, Robert Brown, MD, MPH, James Meschia, MD, Owen A. Ross, PhD, Guillaume Pare, MD, MSc, FRCPC, Mike Chong, MSc, Tatjana Rundek, MD PhD, Katrina Gwinn, MD, Christopher Chen, BMBCh (Oxon), MRCP, FRCP, Jim Koenig, PhD, Eva Giralt, PhD, Danish Saleheen, MBBS, PhD, Frank-Erik de Leeuw, MD, PhD, Karin Klijn, MD, PhD, Yoichiro Kamatani, MD, PhD, Michiaki Kubo, MD, PhD, Yukinori Okada, MD, PhD, Annie Pedersen, MD, Maja Olsson, PhD, Juan José Martín, MD, Huichun Xu, MD, PhD, Eng King Tan, MD, Petrea Frid, MD, Chaeyoung Lee, PhD, David Tregouet, PhD, Thomas Leung, MB, ChB, MRCP, FHKCP, FHKAM, Richard Choy, BSc (Brad.), MSc(Med) (Birm.), PhD (CUHK), Christina Jern, MD, PhD, Keat Wei Loo, BSc, PhD, Gabriel Rinkel, MD, Paulo Franca, PhD, Iscia Cendes, MD, PhD, Caty Carrera, MD, Israel Fernandez-Cadenas, PhD, Joan Montaner, MD, PhD, Helen Kim, PhD, Mayowa Owolabi, MBBS, MSc, DrM, MWACP, FMCP, FAAN, FAS, Reecha Sofat, MD, Mark Bakker, PhD, Ynte Ruigrok, MD, PhD, Allard Hauer, PhD candidate, Sara L. Pulit, PhD, Sander W. van der Laan, PhD, Ryan Irvin, PhD, Murali Sargurupremraj, PhD, Alessandro Pezzini, MD, Foad Abd-Allah, MD, David Liebeskind, MD, Matthew Traylor, PhD, Rhea Tan, BSc (Hons), John Danesh, MD, DPhil, Loes Rutten-Jacobs, PhD, Amanda Donatti, PhD, student, Wagner Avelar, PhD, Joseph Broderick, MD, Daniel Woo, MD, MS, Cathie Sudlow, BMBCh, MSc, DPhil, FRCP, Kristiina Rannikmae, MD, Caitrin Wheeler McDonough, PhD, Tom van Agtmael, PhD, Matthew Walters, MD, MBChB, FRCP, Martin Söderholm, MD, PhD, Erik Lorentzen, Ph.Lic., Sandra Olsson, PhD, MSc, Tara Stanne, PhD, Martina Olsson, MSc, Rufus Akinyemi, PhD, MSc, MWACP, FMCP, Ioana Cotlatciuc, PhD, Patrick McArdle, PhD, Tushar Dave, MSc, Steven Kittner, MD, MPH, John Attia, MD, PhD, James E Faber, PhD, Iona Millwood, DPhil, Elsa Valdés Márquez, PhD, Michelangelo Mancuso, MD, PhD, Riina Vibo, MD, PhD, Janika Korv, MD, PhD, FESO, Jane Maguire, PhD, BN (Hons), BA, RN, Myriam Fornage, PhD, Jennifer Majersik, MD, Adam DeHavenon, MD, Matthew Alexander, MD, Michele Sale, PhD, Andrew Southerland, MD, MSc, Debra Owens, NNP, Bruce Psaty, MD, PhD, W. T. Longstreth, Jr, MD, MPH, Stacey Quintero Wolfe, MD, FAANS, Carl Langefeld, PhD, Carlos Cruchaga, PhD, Jan Konrad, administrative coordinator, Kevin Sheth, MD, Guido Falcone, MD, ScD, MPH, Kathleen Donahue, BS, Alexis N Simpkins, MD, PhD, Tan Wei Liang Byorn, MMBS, student, Bernard Chan, MD, Phil Clatworthy, MD, PhD, Jose Florez, MD, Eric Harshfield, PhD, Atsushi Hozawa, MD, Chung Hsu, MD, PhD, Chaur-Jong Hu, MD, PhD, Laure Ibanez, PhD, Masafumi Ihara, MD, PhD, FACP, Marcos Lange, PhD, Soo Ji Lee, PhD, MPH, I-Hui Lee, MD, PhD, Patricia Musolino, MD, PhD, Hirofumi Nakatomi, MD, PhD, Kwang-Yeol Park, MD, Stephen S Rich, PhD, Chris Riley, MBA, Joohon Sung, MD, PhD, Hideaki Suzuki, MD, PhD, Katie Vo, MD, Kazuo Washida, MD, PhD, Laura Garcia Ibenez, PhD, Agnieszka Slowik, MD, PhD, Albert Hofman, MD, PhD, Ale Algra, MD, MSc, Alex P Reiner, MD, MSc, Alexander S F Doney, PhD, Andreas Gschwendtner, MD, Andreea Ilinca, MD, Anne-Katrin Giese, MD, Arne Lindgren, MD, PhD, Astrid M Vicente, PhD, Bo Norrving, MD, PhD, Børge G Nordestgaard, MD, PhD, DMSc, Braxton D Mitchell, PhD, Bradford B Worrall, MD, MSc, Bruce M Psaty, MD, PhD, Cara L Carty, PhD, Cathie Sudlow, BMBCh, MSc, DPhil, FRCP, Christopher D Anderson, MD, Christopher Levi, MBBS B Med Sci FRACP, Claudia L Satizabal, PhD, Colin N A Palmer, PhD, Dale M Gamble, CCRP, Daniel Woo, MD, MS, Danish Saleheen, MBBS, PhD, E Bernd Ringelstein, MD, FAHA, Einar Valdimarsson, MD, Elizabeth Holliday, PhD, Gail Davies, PhD, Ganesh Chauhan, PhD, Gerard Pasterkamp, MD, PhD, Giorgio Boncoraglio, MD, Gregor Kuhlenbäumer, MD, PhD, Gudmar Thorleifsson, PhD, Guido J Falcone, MD, ScD, MPH, Guillame Pare, MD, MSc, FRCPC, Helena Schmidt, MD, PhD, Hossein Delavaran, MD, PhD, Hugh S Markus, MD, Hugo J Aparicio, MD, Ian Deary, PhD, Ioana Cotlarciuc, PhD, Israel Fernandez-Cadenas, PhD, James Meschia, MD, Jemma C Hopewell, PhD, FESC, Jingmin Liu, MSc, Joan Montaner, MD, PhD, Joanna Pera, MD, PhD, John Cole, MD, MS, John R Attia, MD, PhD, FRACP, FRCPC, Jonathan Rosand, MD, MSc, Jose M Ferro, MD, PhD, Joshua Bis, PhD, Karen Furie, MD, Kari Stefansson, MD, Klaus Berger, MD, PhD, Konstantinos Kostulas, MD, PhD, Kristina Rannikmae, MD, M Arfan Ikram, MD, PhD, Marianne Benn, MD, PhD, Martin Dichgans, MD, Martin Farrall, FRCPath, Massimo Pandolfo, MD, Matthew Traylor, PhD, Matthew Walters, MD, MBChB, FRCP, Michele Sale, PhD, Mike Nalls, PhD, Myriam Fornage, PhD, Natalie R van Zuydam, PhD, Pankaj Sharma, MD, PhD, Patricia Abrantes, PhD, Paul IW de Bakker, PhD, Peter Higgins, FRCP, Peter Lichtner, PhD, Peter M Rothwell, FMedSci, Philippe Amouyel, MD, PhD, Qiong Yang, PhD, Rainer Malik, PhD, Reinhold Schmidt, MD, Robert Clarke, MD, MRCP, FRCP, FFPH, Robin Lemmens, MD, PhD, Sander W van der Laan, PhD, Sara L Pulit, PhD, Sherine Abboud, MD, PhD, Sofia A Oliveira, PhD, Solveig Gretarsdottir, PhD, Stephanie Debette, MD, PhD, Stephen R Williams, PhD, Steve Bevan, BSc, PhD, Steven J Kittner, MD, Sudha Seshadri, MD, Thomas Mosley, PhD, Thomas WK Battey, BS, Turgut Tatlisumak, MD, PhD, Unnur Thorsteinsdottir, PhD, Vincent NS Thijs, MD, PhD, W T Longstreth, MD, Wei Zhao, MD, PhD, Wei-Min Chen, PhD, Yu-Ching Cheng, PhD, Marilyn S. Albert, PhD, Roger L. Albin, MD, Liana G. Apostolova, MD, Steven E. Arnold, MD, Sanjay Asthana, MD, Craig S. Atwood, PhD, Clinton T. Baldwin, PhD, M. Michael Barmada, PhD, Lisa L. Barnes, PhD, Sandra Barral, PhD, Thomas G. Beach, MD, PhD, James T. Becker, PhD, Gary W. Beecham, PhD, Duane Beekly, BS, David A. Bennett, MD, Eileen H. Bigio, MD, Thomas D. Bird, MD, Deborah Blacker, MD, ScD, Bradley F. Boeve, MD, Adam Boxer, MD, PhD, James R. Burke, MD, PhD, Jeffrey M. Burns, MD, MS, Joseph D. Buxbaum, PhD, Goldie S. Byrd, PhD, Guiqing Cai, MD, PhD, Nigel J. Cairns, PhD FRCPath, Laura B. Cantwell, MPH, Chuanhai Cao, PhD, Cynthia M. Carlsson, MD, MS, Regina M. Carney, MD, Minerva M. Carrasquillo, PhD, Steven L. Carroll, MD, PhD, Helena C. Chui, PhD, David G. Clark, MD, David H. Cribbs, PhD, Elizabeth A. Crocco, MD, Carlos Cruchaga, PhD, Philip L. De Jager, MD, PhD, Charles DeCarli, MD, F. Yesim Demirci, MD, Malcolm Dick, Dennis W. Dickson, MD, Ranjan Duara, Md, Nilufer Ertekin-Taner, MD, PhD, Denis A. Evans, MD, Kelley M. Faber, MS, M. Daniele Fallin, PhD, Kenneth B. Fallon, MD, David W. Fardo, PhD, Martin R. Farlow, MD, Lindsay A. Farrer, PhD, Steven Ferris, PhD, Tatiana M. Foroud, PhD, Matthew P. Frosch, MD, PhD, Douglas R. Galasko, MD, Marla Gearing, PhD, Daniel H. Geschwind, MD, PhD, Bernardino Ghetti, MD, John R. Gilbert, PhD, Rodney C.P. Go, PhD, Alison M. Goate, DPhil, Neill R. Graff-Radford, MD, Robert C. Green, MD, MPH, Patrick Griffith, MD, John H. Growdon, MD, Jonathan L. Haines, PhD, Hakon Hakonarson, MD, PhD, Ronald L. Hamilton, MD, Kara L. Hamilton-Nelson, MPH, Vahram Haroutunian, PhD, Lindy E. Harrell, MD, PhD, Lawrence S. Honig, MD, PhD, Ryan M. Huebinger, PhD, Christine M. Hulette, MD, Bradley T. Hyman, MD, PhD, Gregory A. Jicha, MD, PhD, Lee-Way Jin, MD, PhD, Gyungah Jun, PhD, M. Ilyas Kamboh, PhD, Anna Karydas, BA, John S.K. Kauwe, PhD, Jeffrey A. Kaye, MD, Ronald Kim, MD, Neil W. Kowall, MD, Joel H. Kramer, PsyD, Walter A. Kukull, PhD, Brian W. Kunkle, PhD, Frank M. LaFerla, PhD, James J. Lah, MD, PhD, Rosalyn Lang-Walker, PhD, Eric B. Larson, MD, MPH, James B. Leverenz, MD, Allan I. Levey, MD, PhD, Ge Li, MD, PhD, Andrew P. Lieberman, MD, PhD, Mark W. Logue, PhD, Oscar L. Lopez, MD, Kathryn L. Lunetta, PhD, Constantine G. Lyketsos, MD, Wendy J. Mack, PhD, Jennifer J. Manly, PhD, Daniel C. Marson, JD, PhD, Eden R. Martin, PhD, Frank Martiniuk, PhD, Deborah C. Mash, PhD, Eliezer Masliah, MD, Richard Mayeux, MD, Ann C. McKee, MD, Marsel Mesulam, MD, Bruce L. Miller, MD, Carol A. Miller, MD, Joshua W. Miller, PhD, Thomas J. Montine, MD, PhD, John C. Morris, MD, Jill R. Murrell, PhD, Adam C. Naj, PhD, Thomas O. Obisesan, MD, John M. Olichney, MD, Vernon S. Pankratz, PhD, Joseph E. Parisi, MD, Amanda Partch, MS, Henry L. Paulson, MD, PhD, Margaret A. Pericak-Vance, PhD, William Perry, BS, Elaine Peskind, MD, Ronald C. Petersen, MD, PhD, Aimee Pierce, MD, Wayne W. Poon, PhD, Huntington Potter, PhD, Joseph F. Quinn, MD, Ashok Raj, MD, Towfique Raj, PhD, Murray Raskind, MD, Eric M. Reiman, MD, Barry Reisberg, MD, Christiane Reitz, MD, PhD, John M. Ringman, MD, MS, Erik D. Roberson, MD, PhD, Howard J. Rosen, MD, Roger N. Rosenberg, MD, Mark A. Sager, MD, Mary Sano, PhD, Andrew J. Saykin, PsyD, Gerard D. Schellenberg, PhD, Julie A. Schneider, MD, MS, Lon S. Schneider, MD, MS, William W. Seeley, MD, Amanda G. Smith, MD, Joshua A. Sonnen, MD, Salvatore Spina, MD, Robert A. Stern, PhD, Russell H. Swerdlow, MD, Rudolph E. Tanzi, PhD, Tricia A. Thornton-Wells, PhD, John Q. Trojanowski, MD, PhD, Juan C. Troncoso, MD, Debby W. Tsuang, MD, Otto Valladares, MS, Vivianna M. Van Deerlin, MD, PhD, Linda J. Van Eldik, PhD, Badri N. Vardarajan, PhD, MS, Harry V. Vinters, MD, Jean Paul Vonsattel, MD, Li-San Wang, PhD, Sandra Weintraub, PhD, Kathleen A. Welsh-Bohmer, PhD, Jennifer Williamson, MS, MPH, Thomas S. Wingo, MD, Sarah Wishnek, MPH, Randall L. Woltjer, MD, PhD, Clinton B. Wright, MD, MS, Steven G. Younkin, MD, PhD, Chang-En Yu, PhD, Lei Yu, PhD, Ganesh Chauhan, PhD, Audrey Y. Chu, PhD, Myriam Fornage, PhD, Joshua C. Bis, PhD, Aki S. Havulinna, DSc, Muralidharan Sargurupremraj, PhD, Albert Vernon Smith, PhD, Hieab H.H. Adams, MSc, Seung Hoan Choi, MA, Stella Trompet, PhD, Melissa E. Garcia, MPH, Ani Manichaikul, PhD, Alexander Teumer, PhD, Stefan Gustafsson, PhD, Traci M. Bartz, MS, Céline Bellenguez, PhD, Jean Sebastien Vidal, MD, Xueqiu Jian, PhD, Olafur Kjartansson, MD, Kerri L. Wiggins, MS, Claudia L. Satizabal, PhD, Flora Xue, MS, Samuli Ripatti, PhD, Yongmei Liu, PhD, Joris Deelen, PhD, Marcel den Hoed, PhD, Susan R. Heckbert, MD, Kenneth Rice, PhD, Nicholas L. Smith, PhD, Quenna Wong, MS, Hugo J. Aparicio, MD, Julie E. Buring, ScD, Paul M Ridker, MD, Claudine Berr, MD, Jean-François Dartigues, MD, Anders Hamsten, MD, Patrik K. Magnusson, PhD, Nancy L. Pedersen, PhD, Lars Lannfelt, MD, Lars Lind, MD, Cecilia M. Lindgren, PhD, Andrew P. Morris, PhD, Albert Hofman, MD, Peter J. Koudstaal, MD, Marileen LP. Portegies, MD, André G. Uitterlinden, PhD, Anton JM de Craen, PhD, Ian Ford, MD, J. Wouter Jukema, MD, David J Stott, MD, Norrina B. Allen, PhD, Michele M. Sale, PhD, Andrew D Johnson, PhD, David A. Bennett, MD, Philip L. De Jager, MD, PhD, Charles C. White, PhD, Hans Jörgen Grabe, MD, Marcello Ricardo Paulista Markus, MD, Oscar L Lopez, MD, Jerome I. Rotter, MD, Michael A. Nalls, PhD, Rebecca F. Gottesman, MD, Michael E. Griswold, PhD, David S. Knopman, MD, B. Gwen Windham, MD, Alexa Beiser, PhD, Erkki Vartiainen, MD, Curtis R. French, PhD, Tobias Kurth, MD, Bruce M. Psaty, MD, Tamara B. Harris, MD, Stephen S Rich, PhD, Anita L. deStefano, PhD, Carsten Oliver Schmidt, PhD, Veikko Salomaa, MD, Thomas H. Mosley, PhD, Erik Ingelsson, MD, PhD, Cornelia M. van Duijn, PhD, Christophe Tzourio, MD, Lenore J Launer, PhD, M. Arfan Ikram, MD, Daniel I. Chasman, PhD, W. T. Longstreth, Jr, MD, MPH, Sudha Seshadri, MD, Stéphanie Debette, MD, Benjamin F.J. Verhaaren, MD, PhD, Stéphanie Debette, MD, PhD, Joshua C. Bis, PhD, Jennifer A. Smith, PhD, MPH, MA, M. Kamran Ikram, MD, PhD, Hieab H. Adams, MSc, Ashley H. Beecham, MSc, Kumar B. Rajan, PhD, Lorna M. Lopez, PhD, Sandra Barral, PhD, Mark A. van Buchem, MD, PhD, Jeroen van der Grond, PhD, Albert V. Smith, PhD, Katrin Hegenscheid, MD, Neelum T. Aggarwal, MD, Mariza de Andrade, PhD, Elizabeth J. Atkinson, PhD, Marian Beekman, PhD, Alexa S. Beiser, PhD, Susan H. Blanton, PhD, Eric Boerwinkle, PhD, Adam M. Brickman, PhD, R. Nick Bryan, MD, PhD, Ganesh Chauhan, PhD, Christopher P.L.H. Chen, FRCP, Vincent Chouraki, MD, PhD, Anton J.M. de Craen, PhD, Fabrice Crivello, PhD, Ian J. Deary, PhD, Joris Deelen, MSc, Philip L. De Jager, MD, PhD, Carole Dufouil, PhD, Mitchell S.V. Elkind, MD, MSc, Denis A. Evans, MD, Paul Freudenberger, MSc, Rebecca F. Gottesman, MD, PhD, Vilmundur Guðnason, MD, PhD, Mohamad Habes, PhD, Susan R. Heckbert, MD, PhD, Gerardo Heiss, MD, Saima Hilal, MBBS, Edith Hofer, PhD, Albert Hofman, MD, PhD, Carla A. Ibrahim-Verbaas, MD, David S. Knopman, MD, Cora E. Lewis, MD, MSPH, Jiemin Liao, MSc, David C.M. Liewald, BSc, Michelle Luciano, PhD, Aad van der Lugt, MD, PhD, Oliver O. Martinez, PhD, Richard Mayeux, MD, MSc, Bernard Mazoyer, MD, PhD, Mike Nalls, PhD, Matthias Nauck, MD, Wiro J. Niessen, PhD, Ben A. Oostra, PhD, Bruce M. Psaty, MD, PhD, Kenneth M. Rice, PhD, Jerome I. Rotter, MD, Bettina von Sarnowski, MD, Helena Schmidt, MD, PhD, Pamela J. Schreiner, PhD, Maaike Schuur, MD, PhD, Stephen S. Sidney, MD, MPH, Sigurdur Sigurdsson, MSc, P. Eline Slagboom, PhD, David J.M. Stott, MD, John C. van Swieten, MD, PhD, Alexander Teumer, PhD, Anna Maria Töglhofer, MSc, Matthew Traylor, PhD, Stella Trompet, PhD, Stephen T. Turner, MD, Christophe Tzourio, MD, PhD, Hae-Won Uh, PhD, André G. Uitterlinden, PhD, Meike W. Vernooij, MD, PhD, Jing J. Wang, PhD, Tien Y. Wong, MD, PhD, Joanna M. Wardlaw, MD, B. Gwen Windham, MD, Katharina Wittfeld, MS, Christiane Wolf, PhD, Clinton B. Wright, MD, Qiong Yang, PhD, Wei Zhao, MD, PhD, Alex Zijdenbos, PhD, J. Wouter Jukema, MD, PhD, Ralph L. Sacco, MD, Sharon L.R. Kardia, PhD, Philippe Amouyel, MD, PhD, Thomas H. Mosley, PhD, W. T. Longstreth, Jr, MD, MPH, Charles C. DeCarli, MD, Cornelia M. van Duijn, PhD, Reinhold Schmidt, MD, Lenore J. Launer, PhD, Hans J. Grabe, MD, Sudha S. Seshadri, MD, M. Arfan Ikram, MD, PhD, Myriam Fornage, PhD, Joshua C. Bis, PhD, Maryam Kavousi, MD, MSc, Nora Franceschini, MD, MPH, Aaron Isaacs, PhD, Gonçalo R Abecasis, PhD, Ulf Schminke, MD, Wendy Post, MD, Albert V. Smith, PhD, L. Adrienne Cupples, PhD, Hugh S Markus, MD, Reinhold Schmidt, MD, Jennifer E. Huffman, MSc, Terho Lehtimäki, MD, PhD, Jens Baumert, PhD, Thomas Münzel, MD, Susan R. Heckbert, MD, PhD, Abbas Dehghan, MD, PhD, Kari North, PhD, Ben Oostra, PhD, Steve Bevan, PhD, Eva-Maria Stoegerer, MD, Caroline Hayward, PhD, Olli Raitakari, MD, PhD, Christa Meisinger, MD, MPH, Arne Schillert, PhD, Serena Sanna, PhD, Henry Völzke, MD, Yu-Ching Cheng, PhD, Bolli Thorsson, MD, Caroline S. Fox, MD, MS, Kenneth Rice, PhD, Fernando Rivadeneira, MD, PhD, Vijay Nambi, MD, Eran Halperin, PhD, Katja E. Petrovic, MSc, Leena Peltonen, MD, PhD, H. Erich Wichmann, MD, PhD, Renate B. Schnabel, MD, MSc, Marcus Dörr, MD, Afshin Parsa, MD, MPH, Thor Aspelund, PhD, Serkalem Demissie, PhD, Sekar Kathiresan, MD, Muredach P. Reilly, MBBCH, MSCE, Kent Taylor, PhD, Andre Uitterlinden, PhD, David J. Couper, PhD, Matthias Sitzer, MD, Mika Kähönen, MD, PhD, Thomas Illig, PhD, Philipp S. Wild, MD, Marco Orru, MD, Jan Lüdemann, PhD, Alan R. Shuldiner, MD, Gudny Eiriksdottir, MSc, Charles C. White, MPH, Jerome I. Rotter, MD, Albert Hofman, MD, PhD, Jochen Seissler, MD, Tanja Zeller, PhD, Gianluca Usala, PhD, Florian Ernst, PhD, Lenore J. Launer, PhD, Ralph B. D'Agostino, Sr, PhD, Daniel H. O'Leary, MD, Christie Ballantyne, MD, Joachim Thiery, MD, MBA, Andreas Ziegler, Dr. rer. nat. habil., Edward G. Lakatta, MD, Ravi Kumar Chilukoti, MSc, Tamara B. Harris, MD, PhD, Philip A. Wolf, MD, Bruce M. Psaty, MD, PhD, Joseph F Polak, MD, MPH, Xia Li, MD, MPH, Wolfgang Rathmann, MD, MSPH, Manuela Uda, PhD, Eric Boerwinkle, PhD, Norman Klopp, PhD, Helena Schmidt, MD PhD, James F Wilson, DPhil, Jorma Viikari, MD, PhD, Wolfgang Koenig, MD, Stefan Blankenberg, Prof Dr med, Anne B. Newman, MD, MPH, Jacqueline Witteman, PhD, Gerardo Heiss, MD, PhD, Cornelia van Duijn, PhD, Angelo Scuteri, MD, PhD, Georg Homuth, PhD, Braxton D. Mitchell, PhD, Vilmundur Gudnason, MD, PhD, and Christopher J. O’Donnell, MD, MPH, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, and Berr, Claudine
Subjects: Neurology & Neurosurgery, [SDV]Life Sciences [q-bio], Heilaskaði, Clinical Neurology, Stroke Genetics Network (SiGN), the International Stroke Genetics Consortium (ISGC), METASTROKE, Alzheimer's Disease Genetics Consortium (ADGC), and the Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, R1, Article, [SDV] Life Sciences [q-bio], Taugasjúkdómar, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Meta-analyses, Brain infarcts, GWAS, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, ddc:610, Erfðarannsóknir, MRI
Abstract: Publisher's version (útgefin grein), Objective: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. Methods We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n=20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. Results: The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10-8; and LINC00539/ZDHHC20, p = 5.82 × 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p[BI] = 9.38 × 10-25; p [SSBI] = 5.23 × 10-14 for hypertension), smoking (p[BI]= 4.4 × 10-10; p [SSBI] = 1.2 × 10 -4), diabetes (p[BI] = 1.7 × 10 -8; p [SSBI] = 2.8 × 10 -3), previous cardiovascular disease (p [BI] = 1.0 × 10-18; p [SSBI] = 2.3 × 10-7), stroke (p [BI] = 3.9 × 10-69; p [SSBI] = 3.2 × 10 -24), and MRI-defined white matter hyperintensity burden (p [BI]=1.43 × 10-157; p [SSBI] = 3.16 × 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy. Conclusion: In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI., CHAP: R01-AG-11101, R01-AG-030146, NIRP-14-302587. SMART: This study was supported by a grant from the Netherlands Organization for Scientific Research–Medical Sciences (project no. 904-65–095). LBC: The authors thank the LBC1936 participants and the members of the LBC1936 research team who collected and collated the phenotypic and genotypic data. The LBC1936 is supported by Age UK (Disconnected Mind Programme grant). The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1). The brain imaging was performed in the Brain Research Imaging Centre (https://www.ed.ac.uk/clinical-sciences/edinburgh-imaging), a center in the SINAPSE Collaboration (sinapse.ac.uk) supported by the Scottish Funding Council and Chief Scientist Office. Funding from the UK Biotechnology and Biological Sciences Research Council (BBSRC) and the UK Medical Research Council is acknowledged. Genotyping was supported by a grant from the BBSRC (ref. BB/F019394/1). PROSPER: The PROSPER study was supported by an investigator-initiated grant obtained from Bristol-Myers Squibb. Prof. Dr. J.W. Jukema is an Established Clinical Investigator of the Netherlands Heart Foundation (grant 2001 D 032). Support for genotyping was provided by the seventh framework program of the European commission (grant 223004) and by the Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging grant 050-060-810). SCES and SiMES: National Medical Research Council Singapore Centre Grant NMRC/CG/013/2013. C.-Y.C. is supported by the National Medical Research Council, Singapore (CSA/033/2012), Singapore Translational Research Award (STaR) 2013. Dr. Kamran Ikram received additional funding from the Singapore Ministry of Health's National Medical Research Council (NMRC/CSA/038/2013). SHIP: SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs, as well as the Social Ministry of the Federal State of Mecklenburg–West Pomerania, and the network “Greifswald Approach to Individualized Medicine (GANI_MED)” funded by the Federal Ministry of Education and Research (grant 03IS2061A). Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthineers, Erlangen, Germany, and the Federal State of Mecklenburg–West Pomerania. Whole-body MRI was supported by a joint grant from Siemens Healthineers, Erlangen, Germany, and the Federal State of Mecklenburg–West Pomerania. The University of Greifswald is a member of the Caché Campus program of the InterSystems GmbH. OATS (Older Australian Twins Study): OATS was supported by an Australian National Health and Medical Research Council (NHRMC)/Australian Research Council (ARC) Strategic Award (ID401162) and by a NHMRC grant (ID1045325). OATS was facilitated via access to the Australian Twin Registry, which is supported by the NHMRC Enabling Grant 310667. The OATS genotyping was partly supported by a Commonwealth Scientific and Industrial Research Organisation Flagship Collaboration Fund Grant. NOMAS: The Northern Manhattan Study is funded by the NIH grant “Stroke Incidence and Risk Factors in a Tri-Ethnic Region” (NINDS R01NS 29993). TASCOG: NHMRC and Heart Foundation. AGES: The study was funded by the National Institute on Aging (NIA) (N01-AG-12100), Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament), with contributions from the Intramural Research Programs at the NIA, the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Neurological Disorders and Stroke (NINDS) (Z01 HL004607-08 CE). ERF: The ERF study as a part of European Special Populations Research Network (EUROSPAN) was supported by European Commission FP6 STRP grant no. 018947 (LSHG-CT-2006-01947) and also received funding from the European Community's Seventh Framework Programme (FP7/2007–2013)/grant agreement HEALTH-F4-2007-201413 by the European Commission under the programme “Quality of Life and Management of the Living Resources” of 5th Framework Programme (no. QLG2-CT-2002-01254). High-throughput analysis of the ERF data was supported by a joint grant from Netherlands Organization for Scientific Research and the Russian Foundation for Basic Research (NWO-RFBR 047.017.043). Exome sequencing analysis in ERF was supported by the ZonMw grant (project 91111025). Najaf Amin is supported by the Netherlands Brain Foundation (project no. F2013[1]-28). ARIC: The Atherosclerosis Risk in Communities study was performed as a collaborative study supported by NHLBI contracts (HHSN268201100005C, HSN268201100006C, HSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL70825, R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and NIH contract HHSN268200625226C. Infrastructure was partly supported by grant no. UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. This project was also supported by NIH R01 grant NS087541 to M.F. FHS: This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (contracts no. N01-HC-25195 and no. HHSN268201500001I), and its contract with Affymetrix, Inc. for genotyping services (contract no. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. This study was also supported by grants from the NIA (R01s AG033040, AG033193, AG054076, AG049607, AG008122, and U01-AG049505) and the NINDS (R01-NS017950, UH2 NS100605). Dr. DeCarli is supported by the Alzheimer's Disease Center (P30 AG 010129). ASPS: The research reported in this article was funded by the Austrian Science Fund (FWF) grant nos. P20545-P05, P13180, and P20545-B05, by the Austrian National Bank Anniversary Fund, P15435, and the Austrian Ministry of Science under the aegis of the EU Joint Programme–Neurodegenerative Disease Research (JPND) (jpnd.eu). LLS: The Leiden Longevity Study has received funding from the European Union's Seventh Framework Programme (FP7/2007–2011) under grant agreement no. 259679. This study was supported by a grant from the Innovation-Oriented Research Program on Genomics (SenterNovem IGE05007), the Centre for Medical Systems Biology, and the Netherlands Consortium for Healthy Ageing (grant 050-060-810), all in the framework of the Netherlands Genomics Initiative, Netherlands Organization for Scientific Research (NWO), UnileverColworth, and by BBMRI-NL, a Research Infrastructure financed by the Dutch government (NWO 184.021.007). CHS: This CHS research was supported by contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC15103, and HHSN268200960009C and grants U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393, R01HL085251, and R01HL130114 from the NHLBI with additional contribution from NINDS. Additional support was provided through R01AG023629 from the NIA. A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR001881, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Rotterdam Study: The generation and management of GWAS genotype data for the Rotterdam Study is supported by the Netherlands Organisation of Scientific Research (NWO) Investments (no. 175.010.2005.011, 911-03-012). This study is funded by the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/NWO project no. 050-060-810. The Rotterdam Study is funded by Erasmus MC Medical Center and Erasmus MC University, Rotterdam, Netherlands Organization for Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. M.A.I. is supported by an NWO Veni grant (916.13.054). The 3-City Study: The 3-City Study is conducted under a partnership agreement among the Institut National de la Santé et de la Recherche Médicale (INSERM), the University of Bordeaux, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study is also supported by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, Mutuelle Générale de l’Education Nationale (MGEN), Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Programme “Cohortes et collections de données biologiques.” C.T. and S.D. have received investigator-initiated research funding from the French National Research Agency (ANR) and from the Fondation Leducq. S.D. is supported by a starting grant from the European Research Council (SEGWAY), a grant from the Joint Programme of Neurodegenerative Disease research (BRIDGET), from the European Union's Horizon 2020 research and innovation programme under grant agreements No 643417 & No 640643, and by the Initiative of Excellence of Bordeaux University. Part of the computations were performed at the Bordeaux Bioinformatics Center (CBiB), University of Bordeaux. This work was supported by the National Foundation for Alzheimer's Disease and Related Disorders, the Institut Pasteur de Lille, the Labex DISTALZ, and the Centre National de Génotypage. ADGC: The Alzheimer Disease Genetics Consortium is supported by NIH. NIH-NIA supported this work through the following grants: ADGC, U01 AG032984, RC2 AG036528; NACC, U01 AG016976; NCRAD, U24 AG021886; NIA LOAD, U24 AG026395, U24 AG026390; Banner Sun Health Research Institute, P30 AG019610; Boston University, P30 AG013846, U01 AG10483, R01 CA129769, R01 MH080295, R01 AG017173, R01 AG025259, R01AG33193; Columbia University, P50 AG008702, R37 AG015473; Duke University, P30 AG028377, AG05128; Emory University, AG025688; Group Health Research Institute, UO1 AG06781, UO1 HG004610; Indiana University, P30 AG10133; Johns Hopkins University, P50 AG005146, R01 AG020688; Massachusetts General Hospital, P50 AG005134; Mayo Clinic, P50 AG016574; Mount Sinai School of Medicine, P50 AG005138, P01 AG002219; New York University, P30 AG08051, MO1RR00096, UL1 RR029893, 5R01AG012101, 5R01AG022374, 5R01AG013616, 1RC2AG036502, 1R01AG035137; Northwestern University, P30 AG013854; Oregon Health & Science University, P30 AG008017, R01 AG026916; Rush University, P30 AG010161, R01 AG019085, R01 AG15819, R01 AG17917, R01 AG30146; TGen, R01 NS059873; University of Alabama at Birmingham, P50 AG016582, UL1RR02777; University of Arizona, R01 AG031581; University of California, Davis, P30 AG010129; University of California, Irvine, P50 AG016573, P50, P50 AG016575, P50 AG016576, P50 AG016577; University of California, Los Angeles, P50 AG016570; University of California, San Diego, P50 AG005131; University of California, San Francisco, P50 AG023501, P01 AG019724; University of Kentucky, P30 AG028383, AG05144; University of Michigan, P50 AG008671; University of Pennsylvania, P30 AG010124; University of Pittsburgh, P50 AG005133, AG030653; University of Southern California, P50 AG005142; University of Texas Southwestern, P30 AG012300; University of Miami, R01 AG027944, AG010491, AG027944, AG021547, AG019757; University of Washington, P50 AG005136; Vanderbilt University, R01 AG019085; and Washington University, P50 AG005681, P01 AG03991. The Kathleen Price Bryan Brain Bank at Duke University Medical Center is funded by NINDS grant NS39764, NIMH MH60451, and by GlaxoSmithKline. Genotyping of the TGEN2 cohort was supported by Kronos Science. The TGen series was also funded by NIA grant AG041232, the Banner Alzheimer's Foundation, The Johnnie B. Byrd Sr. Alzheimer's Institute, the Medical Research Council, and the state of Arizona and also includes samples from the following sites: Newcastle Brain Tissue Resource (funding via the Medical Research Council [MRC], local NHS trusts, and Newcastle University), MRC London Brain Bank for Neurodegenerative Diseases (funding via the Medical Research Council), South West Dementia Brain Bank (funding via numerous sources including the Higher Education Funding Council for England [HEFCE], Alzheimer's Research Trust [ART], BRACE, as well as North Bristol NHS Trust Research and Innovation Department and DeNDRoN), The Netherlands Brain Bank (funding via numerous sources including Stichting MS Research, Brain Net Europe, Hersenstichting Nederland Breinbrekend Werk, International Parkinson Fonds, Internationale Stiching Alzheimer Onderzoek), Institut de Neuropatologia, Servei Anatomia Patologica, and Universitat de Barcelona). ADNI: Funding for ADNI is through the Northern California Institute for Research and Education by grants from Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson & Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., Alzheimer's Association, Alzheimer's Drug Discovery Foundation, the Dana Foundation, and the National Institute of Biomedical Imaging and Bioengineering and NIA grants U01 AG024904, RC2 AG036535, and K01 AG030514. Support was also provided by the Alzheimer's Association (LAF, IIRG-08-89720; MAP-V, IIRG-05-14147) and the US Department of Veterans Affairs Administration, Office of Research and Development, Biomedical Laboratory Research Program. SiGN: Stroke Genetic Network (SiGN) was supported in part by award nos. U01NS069208 and R01NS100178 from NINDS. Genetics of Early-Onset Stroke (GEOS) Study was supported by the NIH Genes, Environment and Health Initiative (GEI) grant U01 HG004436, as part of the GENEVA consortium under GEI, with additional support provided by the Mid-Atlantic Nutrition and Obesity Research Center (P30 DK072488); and the Office of Research and Development, Medical Research Service, and the Baltimore Geriatrics Research, Education, and Clinical Center of the Department of Veterans Affairs. Genotyping services were provided by the Johns Hopkins University Center for Inherited Disease Research (CIDR), which is fully funded through a federal contract from the NIH to Johns Hopkins University (contract no. HHSN268200782096C). Assistance with data cleaning was provided by the GENEVA Coordinating Center (U01 HG 004446; PI Bruce S. Weir). Study recruitment and assembly of datasets were supported by a Cooperative Agreement with the Division of Adult and Community Health, Centers for Disease Control and Prevention, and by grants from NINDS and the NIH Office of Research on Women's Health (R01 NS45012, U01 NS069208-01). METASTROKE: ASGC: Australian population control data were derived from the Hunter Community Study. This research was funded by grants from the Australian National and Medical Health Research Council (NHMRC Project Grant ID: 569257), the Australian National Heart Foundation (NHF Project Grant ID: G 04S 1623), the University of Newcastle, the Gladys M Brawn Fellowship scheme, and the Vincent Fairfax Family Foundation in Australia. E.G.H. was supported by a Fellowship from the NHF and National Stroke Foundation of Australia (ID: 100071). J.M. was supported by an Australian Postgraduate Award. BRAINS: Bio-Repository of DNA in Stroke (BRAINS) is partly funded by a Senior Fellowship from the Department of Health (UK) to P.S., the Henry Smith Charity, and the UK-India Education Research Institutive (UKIERI) from the British Council. GEOS: Genetics of Early Onset Stroke (GEOS) Study, Baltimore, was supported by GEI Grant U01 HG004436, as part of the GENEVA consortium under GEI, with additional support provided by the Mid-Atlantic Nutrition and Obesity Research Center (P30 DK072488), and the Office of Research and Development, Medical Research Service, and the Baltimore Geriatrics Research, Education, and Clinical Center of the Department of Veterans Affairs. Genotyping services were provided by the Johns Hopkins University Center for Inherited Disease Research (CIDR), which is fully funded through a federal contract from the NIH to the Johns Hopkins University (contract no. HHSN268200782096C). Assistance with data cleaning was provided by the GENEVA Coordinating Center (U01 HG 004446; PI Bruce S. Weir). Study recruitment and assembly of datasets were supported by a Cooperative Agreement with the Division of Adult and Community Health, Centers for Disease Control and Prevention, and by grants from NINDS and the NIH Office of Research on Women's Health (R01 NS45012, U01 NS069208-01). HPS: Heart Protection Study (HPS) (ISRCTN48489393) was supported by the UK MRC, British Heart Foundation, Merck and Co. (manufacturers of simvastatin), and Roche Vitamins Ltd. (manufacturers of vitamins). Genotyping was supported by a grant to Oxford University and CNG from Merck and Co. J.C.H. acknowledges support from the British Heart Foundation (FS/14/55/30806). ISGS: Ischemic Stroke Genetics Study (ISGS)/Siblings With Ischemic Stroke Study (SWISS) was supported in part by the Intramural Research Program of the NIA, NIH project Z01 AG-000954-06. ISGS/SWISS used samples and clinical data from the NIH-NINDS Human Genetics Resource Center DNA and Cell Line Repository (ccr.coriell.org/ninds), human subjects protocol nos. 2003-081 and 2004-147. ISGS/SWISS used stroke-free participants from the Baltimore Longitudinal Study of Aging (BLSA) as controls. The inclusion of BLSA samples was supported in part by the Intramural Research Program of the NIA, NIH project Z01 AG-000015-50, human subjects protocol no. 2003-078. The ISGS study was funded by NIH-NINDS Grant R01 NS-42733 (J.F.M.). The SWISS study was funded by NIH-NINDS Grant R01 NS-39987 (J.F.M.). This study used the high-performance computational capabilities of the Biowulf Linux cluster at the NIH (biowulf.nih.gov). MGH-GASROS: MGH Genes Affecting Stroke Risk and Outcome Study (MGH-GASROS) was supported by NINDS (U01 NS069208), the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research 0775010N, the NIH and NHLBI's STAMPEED genomics research program (R01 HL087676), and a grant from the National Center for Research Resources. The Broad Institute Center for Genotyping and Analysis is supported by grant U54 RR020278 from the National Center for Research resources. Milan: Milano–Besta Stroke Register Collection and genotyping of the Milan cases within CEDIR were supported by the Italian Ministry of Health (grant nos.: RC 2007/LR6, RC 2008/LR6; RC 2009/LR8; RC 2010/LR8; GR-2011-02347041), FP6 LSHM-CT-2007-037273 for the PROCARDIS control samples. WTCCC2: Wellcome Trust Case-Control Consortium 2 (WTCCC2) was principally funded by the Wellcome Trust, as part of the Wellcome Trust Case Control Consortium 2 project (085475/B/08/Z and 085475/Z/08/Z and WT084724MA). The Stroke Association provided additional support for collection of some of the St George's, London cases. The Oxford cases were collected as part of the Oxford Vascular Study, which is funded by the MRC, Stroke Association, Dunhill Medical Trust, National Institute of Health Research (NIHR), and the NIHR Biomedical Research Centre, Oxford. The Edinburgh Stroke Study was supported by the Wellcome Trust (clinician scientist award to C.L.M.S.) and the Binks Trust. Sample processing occurred in the Genetics Core Laboratory of the Wellcome Trust Clinical Research Facility, Western General Hospital, Edinburgh. Much of the neuroimaging occurred in the Scottish Funding Council Brain Imaging Research Centre (https://www.ed.ac.uk/clinical-sciences/edinburgh-imaging), Division of Clinical Neurosciences, University of Edinburgh, a core area of the Wellcome Trust Clinical Research Facility, and part of the SINAPSE (Scottish Imaging Network: A Platform for Scientific Excellence) collaboration (sinapse.ac.uk), funded by the Scottish Funding Council and the Chief Scientist Office. Collection of the Munich cases and data analysis was supported by the Vascular Dementia Research Foundation. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreements no. 666881, SVDs@target (to M.D.) and no. 667375, CoSTREAM (to M.D.); the DFG as part of the Munich Cluster for Systems Neurology (EXC 1010 SyNergy) and the CRC 1123 (B3) (to M.D.); the Corona Foundation (to M.D.); the Fondation Leducq (Transatlantic Network of Excellence on the Pathogenesis of Small Vessel Disease of the Brain) (to M.D.); the e:Med program (e:AtheroSysMed) (to M.D.) and the FP7/2007-2103 European Union project CVgenes@target (grant agreement no. Health-F2-2013-601456) (to M.D.). M.F. and A.H. acknowledge support from the BHF Centre of Research Excellence in Oxford and the Wellcome Trust core award (090532/Z/09/Z). VISP: The GWAS component of the Vitamin Intervention for Stroke Prevention (VISP) study was supported by the US National Human Genome Research Institute (NHGRI), grant U01 HG005160 (PI Michèle Sale and Bradford Worrall), as part of the Genomics and Randomized Trials Network (GARNET). Genotyping services were provided by the Johns Hopkins University Center for Inherited Disease Research (CIDR), which is fully funded through a federal contract from the NIH to Johns Hopkins University. Assistance with data cleaning was provided by the GARNET Coordinating Center (U01 HG005157; PI Bruce S. Weir). Study recruitment and collection of datasets for the VISP clinical trial were supported by an investigator-initiated research grant (R01 NS34447; PI James Toole) from the US Public Health Service, NINDS, Bethesda, MD. Control data obtained through the database of genotypes and phenotypes (dbGAP) maintained and supported by the United States National Center for Biotechnology Information, US National Library of Medicine. WHI: Funding support for WHI-GARNET was provided through the NHGRI GARNET (grant no. U01 HG005152). Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GARNET Coordinating Center (U01 HG005157). Funding support for genotyping, which was performed at the Broad Institute of MIT and Harvard, was provided by the GEI (U01 HG004424). R.L. is a senior clinical investigator of FWO Flanders. F.W.A. is supported by a Dekker scholarship-Junior Staff Member 2014T001–Netherlands Heart Foundation and UCL Hospitals NIHR Biomedical Research Centre.
Published: 2019

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415 results on '"Joseph F Polak"'

401. JENNER CENTENARY AT WARSAW

402. Racial and Ethnic Differences in the Association Between Classical Cardiovascular Risk Factors and Common Carotid Intima‐Media Thickness: An Individual Participant Data Meta‐Analysis

403. Coronary Artery Disease Events and Carotid Intima‐Media Thickness in Type 1 Diabetes in the DCCT/EDIC Cohort

404. The progression of carotid atherosclerosis and imaging markers of dementia

405. Serum Non-Esterified Fatty Acids, Carotid Artery Intima-Media Thickness and Flow-Mediated Dilation in Older Adults: The Cardiovascular Health Study (CHS)

406. Risk Factors for Incident Carotid Artery Revascularization among Older Adults: The Cardiovascular Health Study

407. Detailed analysis of association between common single nucleotide polymorphisms and subclinical atherosclerosis: The Multi-ethnic Study of Atherosclerosis

408. Comparison of Carotid Plaque Score and Coronary Artery Calcium Score for Predicting Cardiovascular Disease Events: The Multi‐Ethnic Study of Atherosclerosis

409. Carotid Intima‐Media Thickness Score, Positive Coronary Artery Calcium Score, and Incident Coronary Heart Disease: The Multi‐Ethnic Study of Atherosclerosis

410. Concentration of Smaller High‐Density Lipoprotein Particle (HDL‐P) Is Inversely Correlated With Carotid Intima Media Thickening After Confounder Adjustment: The Multi Ethnic Study of Atherosclerosis (MESA)

411. Carotid Intima‐Media Thickness and Arterial Stiffness and the Risk of Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study, Multi‐Ethnic Study of Atherosclerosis (MESA), and the Rotterdam Study

412. Carotid Atherosclerosis and Cerebral Microbleeds: The Framingham Heart Study

413. Variants at the APOA5 locus, association with carotid atherosclerosis, and modification by obesity: the Framingham Study

414. Association of APOE genotype with carotid atherosclerosis in men and women

415. Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting

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