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Results: 1 to 10 of 201

Publication Record


Coronary Artery Calcium From Early Adulthood to Middle Age and Left Ventricular Structure and Function.
Yared GS, Moreira HT, Ambale-Venkatesh B, Vasconcellos HD, Nwabuo CC, Ostovaneh MR, Reis JP, Lloyd-Jones DM, Schreiner PJ, Lewis CE, Sidney S, Carr JJ, Gidding SS, Lima JAC
(2019) Circ Cardiovasc Imaging 12: e009228
MeSH Terms: Age Factors, Coronary Artery Disease, Coronary Vessels, Female, Heart Ventricles, Humans, Male, Middle Aged, Prospective Studies, Risk Factors, Tomography, X-Ray Computed, Vascular Calcification, Ventricular Dysfunction, Left
Show Abstract · Added January 10, 2020
Background The relationship of coronary artery calcium (CAC) with adverse cardiac remodeling is not well established. We aimed to study the association of CAC in middle age and change in CAC from early adulthood to middle age with left ventricular (LV) function. Methods CAC score was measured by computed tomography at CARDIA study (Coronary Artery Risk Development in Young Adults) year-15 examination and at year-25 examination (Y25) in 3043 and 3189 participants, respectively. CAC score was assessed as a continuous variable and log-transformed to account for nonlinearity. Change in CAC from year-15 examination to Y25 was evaluated as the absolute difference of log-transformed CAC from year-15 examination to Y25. LV structure and function were evaluated by echocardiography at Y25. Results At Y25, mean age was 50.1±3.6 years, 56.6% women, 52.4% black. In the multivariable analysis at Y25, higher CAC was related to higher LV mass (β=1.218; adjusted P=0.007), higher LV end-diastolic volume (β=0.811; adjusted P=0.007), higher LV end-systolic volume (β=0.350; adjusted P=0.048), higher left atrial volume (β=0.214; adjusted P=0.009), and higher E/e' ratio (β=0.059; adjusted P=0.014). CAC was measured at both year-15 examination and Y25 in 2449 individuals. Higher change in CAC score during follow-up was independently related to higher LV mass index in blacks (β=4.789; adjusted P<0.001), but not in whites (β=1.051; adjusted P=0.283). Conclusions Higher CAC in middle age is associated with higher LV mass and volumes and worse LV diastolic function. Being free of CAC from young adulthood to middle age correlates to better LV function at middle age. Higher change in CAC score during follow-up is independently related to higher LV mass index in blacks.
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13 MeSH Terms
Connections Between Clonal Hematopoiesis, Cardiovascular Disease, and Cancer: A Review.
Calvillo-Argüelles O, Jaiswal S, Shlush LI, Moslehi JJ, Schimmer A, Barac A, Thavendiranathan P
(2019) JAMA Cardiol 4: 380-387
MeSH Terms: Adult, Aged, Aged, 80 and over, Cardiovascular Diseases, Clonal Evolution, Coronary Artery Disease, Hematopoiesis, Humans, Inflammation, Middle Aged, Mutation, Neoplasms, Prevalence, Risk Factors, Stroke
Show Abstract · Added November 12, 2019
Importance - Clonal hematopoiesis (CH) has been recently described as a novel driver for cancer and cardiovascular disease (CVD). Clonal hematopoiesis is a common, age-associated disorder marked by expansion of hematopoietic clones carrying recurrent somatic mutations. Current literature suggests that patients with CH have a higher risk of subsequent hematological malignant conditions and mortality attributable to excess CVD. This review discusses the association of cancer with CVD with CH as a potential unifying factor.
Observations - The prevalence of CH varies based on the sequencing depth, diagnostic criteria, and patient age and ranges from less than 1% in those younger than 40 years to more than 15% to 20% in those 90 years and older. Clonal hematopoiesis is associated with a 0.5% to 1.0% absolute annual risk of hematological malignant condition and a 2-fold to 4-fold higher risk of coronary artery disease, stroke, and CVD deaths, independent of traditional cardiovascular risk factors. In fact, CH appears to have a relative risk similar to that of traditional cardiovascular risk factors for CVD. Experimental studies suggest that the link between CVD and CH is causal, with inflammation as 1 potential mechanism. There may be also a link between CH and CVD in survivors of cancer; however, data to support this association are currently limited.
Conclusions and Relevance - Clonal hematopoiesis represents a premalignant state, with carriers having an increased risk of hematological malignant conditions. Although most carriers will not develop a malignant condition, CH confers an increased risk of CVD, possibly via inflammation. Clonal hematopoiesis may also contribute to CVD in survivors of cancer, although this hypothesis requires validation. Clinically, as advanced sequencing techniques become available, CH may pave the way for precision medicine in the field of cardio-oncology.
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15 MeSH Terms
Associations of Unhealthy Food Environment With the Development of Coronary Artery Calcification: The CARDIA Study.
Kelman J, Pool LR, Gordon-Larsen P, Carr JJ, Terry JG, Rana JS, Kershaw KN
(2019) J Am Heart Assoc 8: e010586
MeSH Terms: Adolescent, Adult, Coronary Angiography, Coronary Artery Disease, Coronary Vessels, Disease Progression, Female, Follow-Up Studies, Food Supply, Forecasting, Humans, Incidence, Male, Prospective Studies, Restaurants, Risk Assessment, Risk Factors, United States, Vascular Calcification, Young Adult
Show Abstract · Added April 3, 2019
Background While prior studies have linked the neighborhood environment and development of subclinical atherosclerosis, it is unknown whether living in neighborhoods with greater availability of "unhealthy" food outlets (fast-food chain restaurants and convenience stores) is associated with risk of developing coronary artery calcification ( CAC ). Methods and Results We included 2706 CARDIA study (Coronary Artery Risk Development in Young Adults) participants who underwent CAC measurement during follow-up years 15 (2000-2001), 20 (2005-2006), and 25 (2010-2011). Neighborhood features examined included percentage of all food outlets that were convenience stores and fast-food chain restaurants within a 3-km Euclidean buffer distance from each participant's residence. Econometric fixed effects models, which by design control for all time-invariant covariates, were used to model the longitudinal association between simultaneous within-person change in percentage food outlet and change in CAC . At baseline (year 15), 9.7% of participants had prevalent CAC . During 10 years of follow-up, 21.1% of participants developed CAC . Each 1-SD increase in percentage of convenience stores was associated with a 1.34 higher odds of developing CAC (95% CI : 1.04, 1.72) after adjusting for individual- and neighborhood-level covariates; however, there was no significant association between increased percentage of fast-food chain restaurants and developing CAC (odds ratio=1.15; 95% CI : 0.96, 1.38). There were no significant associations between increases in either food outlet percentage and progression of CAC . Conclusions Our findings suggest that increases in the relative availability of convenience stores in participants' neighborhoods is related to the development of CAC over time.
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20 MeSH Terms
Calcium Scoring for Cardiovascular Computed Tomography: How, When and Why?
Carr JJ
(2019) Radiol Clin North Am 57: 1-12
MeSH Terms: Cardiac-Gated Imaging Techniques, Cardiomyopathies, Coronary Artery Disease, Disease Progression, Humans, Radiographic Image Interpretation, Computer-Assisted, Risk Assessment, Tomography, X-Ray Computed
Show Abstract · Added January 10, 2020
Cardiovascular disease is the leading cause of death in the United States and worldwide. Despite major advances in the treatment of acute myocardial infarction, enhanced prevention of ischemic heart disease remains critical to improving the health of individuals and communities. The computed tomographic coronary artery calcium score is an established imaging biomarker that identifies the presence and amount of coronary atherosclerosis in an individual and their future risk for clinical cardiovascular disease and premature cardiovascular death. This article describes the process of performing a computed tomography scan for coronary artery calcium, quantifying the score and interpreting the results.
Copyright © 2018 Elsevier Inc. All rights reserved.
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Associations of coronary artery calcified plaque density with mortality in type 2 diabetes: the Diabetes Heart Study.
Raffield LM, Cox AJ, Criqui MH, Hsu FC, Terry JG, Xu J, Freedman BI, Carr JJ, Bowden DW
(2018) Cardiovasc Diabetol 17: 67
MeSH Terms: Adult, African Continental Ancestry Group, Aged, Aged, 80 and over, Coronary Angiography, Coronary Artery Disease, Coronary Vessels, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Female, Humans, Male, Middle Aged, Plaque, Atherosclerotic, Prognosis, Risk Factors, United States, Vascular Calcification
Show Abstract · Added September 11, 2018
BACKGROUND - Coronary artery calcified plaque (CAC) is strongly predictive of cardiovascular disease (CVD) events and mortality, both in general populations and individuals with type 2 diabetes at high risk for CVD. CAC is typically reported as an Agatston score, which is weighted for increased plaque density. However, the role of CAC density in CVD risk prediction, independently and with CAC volume, remains unclear.
METHODS - We examined the role of CAC density in individuals with type 2 diabetes from the family-based Diabetes Heart Study and the African American-Diabetes Heart Study. CAC density was calculated as mass divided by volume, and associations with incident all-cause and CVD mortality [median follow-up 10.2 years European Americans (n = 902, n = 286 deceased), 5.2 years African Americans (n = 552, n = 93 deceased)] were examined using Cox proportional hazards models, independently and in models adjusted for CAC volume.
RESULTS - In European Americans, CAC density, like Agatston score and volume, was consistently associated with increased risk of all-cause and CVD mortality (p ≤ 0.002) in models adjusted for age, sex, statin use, total cholesterol, HDL, systolic blood pressure, high blood pressure medication use, and current smoking. However, these associations were no longer significant when models were additionally adjusted for CAC volume. CAC density was not significantly associated with mortality, either alone or adjusted for CAC volume, in African Americans.
CONCLUSIONS - CAC density is not associated with mortality independent from CAC volume in European Americans and African Americans with type 2 diabetes.
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18 MeSH Terms
Coronary Artery Calcium Scores and Atherosclerotic Cardiovascular Disease Risk Stratification in Smokers.
Leigh A, McEvoy JW, Garg P, Carr JJ, Sandfort V, Oelsner EC, Budoff M, Herrington D, Yeboah J
(2019) JACC Cardiovasc Imaging 12: 852-861
MeSH Terms: Aged, Aged, 80 and over, Atherosclerosis, Computed Tomography Angiography, Coronary Angiography, Coronary Artery Disease, Early Detection of Cancer, Female, Humans, Incidence, Incidental Findings, Lung Neoplasms, Male, Middle Aged, Plaque, Atherosclerotic, Predictive Value of Tests, Prevalence, Prognosis, Radiography, Thoracic, Risk Assessment, Risk Factors, Smokers, Smoking, Time Factors, United States, Vascular Calcification
Show Abstract · Added January 10, 2020
OBJECTIVES - This study assessed the utility of the pooled cohort equation (PCE) and/or coronary artery calcium (CAC) for atherosclerotic cardiovascular disease (ASCVD) risk assessment in smokers, especially those who were lung cancer screening eligible (LCSE).
BACKGROUND - The U.S. Preventive Services Task Force recommended and the Centers for Medicare & Medicaid Services currently pays for annual screening for lung cancer with low-dose computed tomography scans in a specified group of cigarette smokers. CAC can be obtained from these low-dose scans. The incremental utility of CAC for ASCVD risk stratification remains unclear in this high-risk group.
METHODS - Of 6,814 MESA (Multi-Ethnic Study of Atherosclerosis) participants, 3,356 (49.2% of total cohort) were smokers (2,476 former and 880 current), and 14.3% were LCSE. Kaplan-Meier, Cox proportional hazards, area under the curve, and net reclassification improvement (NRI) analyses were used to assess the association between PCE and/or CAC and incident ASCVD. Incident ASCVD was defined as coronary death, nonfatal myocardial infarction, or fatal or nonfatal stroke.
RESULTS - Smokers had a mean age of 62.1 years, 43.5% were female, and all had a mean of 23.0 pack-years of smoking. The LCSE sample had a mean age of 65.3 years, 39.1% were female, and all had a mean of 56.7 pack-years of smoking. After a mean of 11.1 years of follow-up 13.4% of all smokers and 20.8% of LCSE smokers had ASCVD events; 6.7% of all smokers and 14.2% of LCSE smokers with CAC = 0 had an ASCVD event during the follow-up. One SD increase in the PCE 10-year risk was associated with a 68% increase risk for ASCVD events in all smokers (hazard ratio: 1.68; 95% confidence interval: 1.57 to 1.80) and a 22% increase in risk for ASCVD events in the LCSE smokers (hazard ratio: 1.22; 95% confidence interval: 1.00 to 1.47). CAC was associated with increased ASCVD risk in all smokers and in LCSE smokers in all the Cox models. The C-statistic of the PCE for ASCVD was higher in all smokers compared with LCSE smokers (0.693 vs. 0.545). CAC significantly improved the C-statistics of the PCE in all smokers but not in LCSE smokers. The event and nonevent net reclassification improvements for all smokers and LCSE smokers were 0.018 and -0.126 versus 0.16 and -0.196, respectively.
CONCLUSIONS - In this well-characterized, multiethnic U.S. cohort, CAC was predictive of ASCVD in all smokers and in LCSE smokers but modestly improved discrimination over and beyond the PCE. However, 6.7% of all smokers and 14.2% of LCSE smokers with CAC = 0 had an ASCVD event during follow-up.
Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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26 MeSH Terms
Duration of Diabetes and Prediabetes During Adulthood and Subclinical Atherosclerosis and Cardiac Dysfunction in Middle Age: The CARDIA Study.
Reis JP, Allen NB, Bancks MP, Carr JJ, Lewis CE, Lima JA, Rana JS, Gidding SS, Schreiner PJ
(2018) Diabetes Care 41: 731-738
MeSH Terms: Adolescent, Adult, Asymptomatic Diseases, Atherosclerosis, Cardiovascular Diseases, Coronary Artery Disease, Diabetes Mellitus, Diabetic Angiopathies, Disease Progression, Echocardiography, Female, Heart Ventricles, Humans, Longitudinal Studies, Male, Middle Aged, Prediabetic State, Risk Factors, Time Factors, Tomography, X-Ray Computed, Young Adult
Show Abstract · Added January 10, 2020
OBJECTIVE - To determine whether the duration of diabetes and duration of prediabetes estimated during a 25-year period in early adulthood are each independently associated with coronary artery calcified plaque (CAC) and abnormalities in left ventricular structure and function later in life.
RESEARCH DESIGN AND METHODS - Participants were 3,628 white and black adults aged 18-30 years without diabetes or prediabetes at baseline (1985-1986) in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Durations of diabetes and prediabetes were estimated based on their identification at examinations 7, 10, 15, 20, and 25 years later. CAC was identified by computed tomography at years 15, 20, and 25. Left ventricular structure and function were measured via echocardiogram at year 25.
RESULTS - Of the 3,628 individuals, 12.7% and 53.8% developed diabetes and prediabetes, respectively; average (SD) duration was 10.7 (10.7) years and 9.5 (5.4) years. After adjustment for sociodemographic characteristics and other cardiovascular risk factors, and mutual adjustment for each other, the hazard ratio for the presence of CAC was 1.15 (95% CI 1.06, 1.25) and 1.07 (1.01, 1.13) times higher for each 5-year-longer duration of diabetes and prediabetes, respectively. Diabetes and prediabetes duration were associated with worse subclinical systolic function (longitudinal strain [ < 0.001 for both]) and early diastolic relaxation (e' [ 0.004 and 0.002, respectively]). Duration of diabetes was also associated with a higher diastolic filling pressure (E-to-e' ratio [ 0.001]).
CONCLUSIONS - Durations of diabetes and prediabetes during adulthood are both independently associated with subclinical atherosclerosis and left ventricular systolic and diastolic dysfunction in middle age.
© 2018 by the American Diabetes Association.
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Relation of Ectopic Fat with Atherosclerotic Cardiovascular Disease Risk Score in South Asians Living in the United States (from the Mediators of Atherosclerosis in South Asians Living in America [MASALA] Study).
Mongraw-Chaffin M, Gujral UP, Kanaya AM, Kandula NR, Carr JJ, Anderson CAM
(2018) Am J Cardiol 121: 315-321
MeSH Terms: Adipose Tissue, Aged, Asian Americans, Choristoma, Coronary Artery Disease, Female, Humans, Longitudinal Studies, Male, Middle Aged, Tomography, X-Ray Computed, United States
Show Abstract · Added January 10, 2020
Few studies have investigated the association between ectopic fat from different depots and cardiovascular risk scores and their components in the same population, and none have investigated these relations in South Asians. In a cross-sectional analysis of 796 participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study who had measurements of visceral, subcutaneous, pericardial, hepatic, and intermuscular fat from abdominal and cardiac computed tomography scans, we used linear regression to determine the associations of 1 standard deviation difference in each ectopic fat depot with pooled cohort risk score and its components. Pericardial and visceral fat were more strongly associated with the pooled cohort risk score (3.1%, 95% confidence interval [CI] 2.5 to 3.7, and 2.7%, 95% CI 2.1 to 3.3, respectively) and components than intermuscular fat (2.3%, 95% CI 1.7 to 3.0); subcutaneous fat was inversely associated with the pooled cohort risk score (-2.6%, 95% CI -3.2 to 1.9) and hepatic fat attenuation was not linearly associated with the pooled cohort risk score when mutually adjusted (-0.3%, 95% CI -0.9 to 0.4). Associations for risk factor components differed by fat depot. In conclusion, subcutaneous and hepatic fat may have different functions than fat stored in other depots in South Asians. Determining whether these relations are heterogeneous by race may help elucidate the mechanisms underlying CVD disparities.
Copyright © 2017 Elsevier Inc. All rights reserved.
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High-Density Lipoprotein Cholesterol Concentration and Acute Kidney Injury After Cardiac Surgery.
Smith LE, Smith DK, Blume JD, Linton MF, Billings FT
(2017) J Am Heart Assoc 6:
MeSH Terms: Acute Kidney Injury, Aged, Aged, 80 and over, Atorvastatin, Cardiac Surgical Procedures, Cholesterol, HDL, Coronary Artery Disease, Dose-Response Relationship, Drug, Double-Blind Method, Female, Follow-Up Studies, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Kidney Function Tests, Male, Middle Aged, Postoperative Complications, Postoperative Period, Preoperative Period, Risk Factors, Treatment Outcome
Show Abstract · Added April 10, 2018
BACKGROUND - Acute kidney injury (AKI) after cardiac surgery is associated with increased short- and long-term mortality. Inflammation, oxidative stress, and endothelial dysfunction and damage play important roles in the development of AKI. High-density lipoproteins (HDLs) have anti-inflammatory and antioxidant properties and improve endothelial function and repair. Statins enhance HDL's anti-inflammatory and antioxidant capacities. We hypothesized that a higher preoperative HDL cholesterol concentration is associated with decreased AKI after cardiac surgery and that perioperative statin exposure potentiates this association.
METHODS AND RESULTS - We tested our hypothesis in 391 subjects from a randomized clinical trial of perioperative atorvastatin to reduce AKI after cardiac surgery. A 2-component latent variable mixture model was used to assess the association between preoperative HDL cholesterol concentration and postoperative change in serum creatinine, adjusted for known AKI risk factors and suspected confounders. Interaction terms were used to examine the effects of preoperative statin use, preoperative statin dose, and perioperative atorvastatin treatment on the association between preoperative HDL and AKI. A higher preoperative HDL cholesterol concentration was independently associated with a decreased postoperative serum creatinine change (=0.02). The association between a high HDL concentration and an attenuated increase in serum creatinine was strongest in long-term statin-using patients (=0.008) and was further enhanced with perioperative atorvastatin treatment (=0.004) and increasing long-term statin dose (=0.003).
CONCLUSIONS - A higher preoperative HDL cholesterol concentration was associated with decreased AKI after cardiac surgery. Preoperative and perioperative statin treatment enhanced this association, demonstrating that pharmacological potentiation is possible during the perioperative period.
CLINICAL TRIAL REGISTRATION - URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00791648.
© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
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21 MeSH Terms
Exome-wide association study of plasma lipids in >300,000 individuals.
Liu DJ, Peloso GM, Yu H, Butterworth AS, Wang X, Mahajan A, Saleheen D, Emdin C, Alam D, Alves AC, Amouyel P, Di Angelantonio E, Arveiler D, Assimes TL, Auer PL, Baber U, Ballantyne CM, Bang LE, Benn M, Bis JC, Boehnke M, Boerwinkle E, Bork-Jensen J, Bottinger EP, Brandslund I, Brown M, Busonero F, Caulfield MJ, Chambers JC, Chasman DI, Chen YE, Chen YI, Chowdhury R, Christensen C, Chu AY, Connell JM, Cucca F, Cupples LA, Damrauer SM, Davies G, Deary IJ, Dedoussis G, Denny JC, Dominiczak A, Dubé MP, Ebeling T, Eiriksdottir G, Esko T, Farmaki AE, Feitosa MF, Ferrario M, Ferrieres J, Ford I, Fornage M, Franks PW, Frayling TM, Frikke-Schmidt R, Fritsche LG, Frossard P, Fuster V, Ganesh SK, Gao W, Garcia ME, Gieger C, Giulianini F, Goodarzi MO, Grallert H, Grarup N, Groop L, Grove ML, Gudnason V, Hansen T, Harris TB, Hayward C, Hirschhorn JN, Holmen OL, Huffman J, Huo Y, Hveem K, Jabeen S, Jackson AU, Jakobsdottir J, Jarvelin MR, Jensen GB, Jørgensen ME, Jukema JW, Justesen JM, Kamstrup PR, Kanoni S, Karpe F, Kee F, Khera AV, Klarin D, Koistinen HA, Kooner JS, Kooperberg C, Kuulasmaa K, Kuusisto J, Laakso M, Lakka T, Langenberg C, Langsted A, Launer LJ, Lauritzen T, Liewald DCM, Lin LA, Linneberg A, Loos RJF, Lu Y, Lu X, Mägi R, Malarstig A, Manichaikul A, Manning AK, Mäntyselkä P, Marouli E, Masca NGD, Maschio A, Meigs JB, Melander O, Metspalu A, Morris AP, Morrison AC, Mulas A, Müller-Nurasyid M, Munroe PB, Neville MJ, Nielsen JB, Nielsen SF, Nordestgaard BG, Ordovas JM, Mehran R, O'Donnell CJ, Orho-Melander M, Molony CM, Muntendam P, Padmanabhan S, Palmer CNA, Pasko D, Patel AP, Pedersen O, Perola M, Peters A, Pisinger C, Pistis G, Polasek O, Poulter N, Psaty BM, Rader DJ, Rasheed A, Rauramaa R, Reilly DF, Reiner AP, Renström F, Rich SS, Ridker PM, Rioux JD, Robertson NR, Roden DM, Rotter JI, Rudan I, Salomaa V, Samani NJ, Sanna S, Sattar N, Schmidt EM, Scott RA, Sever P, Sevilla RS, Shaffer CM, Sim X, Sivapalaratnam S, Small KS, Smith AV, Smith BH, Somayajula S, Southam L, Spector TD, Speliotes EK, Starr JM, Stirrups KE, Stitziel N, Strauch K, Stringham HM, Surendran P, Tada H, Tall AR, Tang H, Tardif JC, Taylor KD, Trompet S, Tsao PS, Tuomilehto J, Tybjaerg-Hansen A, van Zuydam NR, Varbo A, Varga TV, Virtamo J, Waldenberger M, Wang N, Wareham NJ, Warren HR, Weeke PE, Weinstock J, Wessel J, Wilson JG, Wilson PWF, Xu M, Yaghootkar H, Young R, Zeggini E, Zhang H, Zheng NS, Zhang W, Zhang Y, Zhou W, Zhou Y, Zoledziewska M, Charge Diabetes Working Group, EPIC-InterAct Consortium, EPIC-CVD Consortium, GOLD Consortium, VA Million Veteran Program, Howson JMM, Danesh J, McCarthy MI, Cowan CA, Abecasis G, Deloukas P, Musunuru K, Willer CJ, Kathiresan S
(2017) Nat Genet 49: 1758-1766
MeSH Terms: Coronary Artery Disease, Diabetes Mellitus, Type 2, Exome, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Variation, Genotype, Humans, Lipids, Macular Degeneration, Phenotype, Risk Factors
Show Abstract · Added March 14, 2018
We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.
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12 MeSH Terms