Center for Human Genetic Research

Boston, MA, United States

Center for Human Genetic Research

Boston, MA, United States
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Jaiswal S.,Harvard University | Jaiswal S.,Dana-Farber Cancer Institute | Fontanillas P.,The Broad Institute of MIT and Harvard | Flannick J.,CSIC - Biological Research Center | And 37 more authors.
New England Journal of Medicine | Year: 2014

Background The incidence of hematologic cancers increases with age. These cancers are associated with recurrent somatic mutations in specific genes. We hypothesized that such mutations would be detectable in the blood of some persons who are not known to have hematologic disorders.METHODS We analyzed whole-exome sequencing data from DNA in the peripheral-blood cells of 17, 182 persons who were unselected for hematologic phenotypes. We looked for somatic mutations by identifying previously characterized single-nucleotide variants and small insertions or deletions in 160 genes that are recurrently mutated in hematologic cancers. The presence of mutations was analyzed for an association with hematologic phenotypes, survival, and cardiovascular events.RESULTS Detectable somatic mutations were rare in persons younger than 40 years of age but rose appreciably in frequency with age. Among persons 70 to 79 years of age, 80 to 89 years of age, and 90 to 108 years of age, these clonal mutations were observed in 9.5% (219 of 2300 persons), 11.7% (37 of 317), and 18.4% (19 of 103), respectively. The majority of the variants occurred in three genes: DNMT3A, TET2, and ASXL1. The presence of a somatic mutation was associated with an increase in the risk of hematologic cancer (hazard ratio, 11.1; 95% confidence interval [CI], 3.9 to 32.6), an increase in all-cause mortality (hazard ratio, 1.4; 95% CI, 1.1 to 1.8), and increases in the risks of incident coronary heart disease (hazard ratio, 2.0; 95% CI, 1.2 to 3.4) and ischemic stroke (hazard ratio, 2.6; 95% CI, 1.4 to 4.8).CONCLUSIONS Age-related clonal hematopoiesis is a common condition that is associated with increases in the risk of hematologic cancer and in all-cause mortality, with the latter possibly due to an increased risk of cardiovascular disease. Copyright © 2014 Massachusetts Medical Society. All rights reserved.


Wu O.,Massachusetts General Hospital | Cloonan L.,Kistler Stroke Research Center | Mocking S.J.T.,Massachusetts General Hospital | Bouts M.J.R.J.,Massachusetts General Hospital | And 10 more authors.
Stroke | Year: 2015

Background and Purpose - Acute infarct volume, often proposed as a biomarker for evaluating novel interventions for acute ischemic stroke, correlates only moderately with traditional clinical end points, such as the modified Rankin Scale. We hypothesized that the topography of acute stroke lesions on diffusion-weighted magnetic resonance imaging may provide further information with regard to presenting stroke severity and long-term functional outcomes. Methods - Data from a prospective stroke repository were limited to acute ischemic stroke subjects with magnetic resonance imaging completed within 48 hours from last known well, admission NIH Stroke Scale (NIHSS), and 3-to-6 months modified Rankin Scale scores. Using voxel-based lesion symptom mapping techniques, including age, sex, and diffusion-weighted magnetic resonance imaging lesion volume as covariates, statistical maps were calculated to determine the significance of lesion location for clinical outcome and admission stroke severity. Results - Four hundred ninety subjects were analyzed. Acute stroke lesions in the left hemisphere were associated with more severe NIHSS at admission and poor modified Rankin Scale at 3 to 6 months. Specifically, injury to white matter (corona radiata, internal and external capsules, superior longitudinal fasciculus, and uncinate fasciculus), postcentral gyrus, putamen, and operculum were implicated in poor modified Rankin Scale. More severe NIHSS involved these regions, as well as the amygdala, caudate, pallidum, inferior frontal gyrus, insula, and precentral gyrus. Conclusions - Acute lesion topography provides important insights into anatomic correlates of admission stroke severity and poststroke outcomes. Future models that account for infarct location in addition to diffusion-weighted magnetic resonance imaging volume may improve stroke outcome prediction and identify patients likely to benefit from aggressive acute intervention and personalized rehabilitation strategies. © 2015 American Heart Association, Inc.


News Article | November 13, 2016
Site: www.eurekalert.org

It is well known that following a healthy lifestyle -- not smoking, avoiding excess weight and getting regular exercise - can reduce the risk of heart disease. But what about people who have inherited gene variants known to increase risk? A study led by Massachusetts General Hospital (MGH) investigators has found that, even among those at high genetic risk, following a healthy lifestyle can cut in half the probability of a heart attack or similar event. Their report is receiving early online publication in the New England Journal of Medicine to coincide with a presentation at the American Heart Association (AHA) Scientific Sessions. "The basic message of our study is that DNA is not destiny," says Sekar Kathiresan, MD, director of the Center for Human Genetic Research at Massachusetts General Hospital (MGH), senior author of the NEJM report. "Many individuals - both physicians and members of the general public -- have looked on genetic risk as unavoidable, but for heart attack that does not appear to be the case." In order to investigate whether a healthy lifestyle can mitigate genetic risk, the multi-institutional research team analyzed genetic and clinical data from more than 55,000 participants in four large-scale studies. Three of these -- the Atherosclerosis Risk in Communities Study, the Women's Genome Health Study, and the Malmö Diet and Cancer Study -- are prospective studies that have followed participants for up to 20 years. The fourth, the BioImage Study, assessed a variety of risk factors, including the presence of atherosclerotic plaques in the coronary arteries when participants joined the study. Each participant in the current analysis was assigned a genetic risk score, based on whether they carried any of 50 gene variants that previous studies associated with elevated heart attack risk. Based on data gathered when participants entered each study, the investigators used four AHA-defined lifestyle factors -- no current smoking; lack of obesity, defined as a body mass index less than 30; physical exercise at least once a week, and a healthy dietary pattern -- to determine a lifestyle score, whether participants had a favorable (three or four healthy factors), intermediate (two factors) or unfavorable (one or no healthy factors) lifestyle. For participants in the prospective studies, the research team investigated how each individual's genetic risk score and lifestyle factors related to the incidence of heart attack, the need for procedures designed to open blocked coronary arteries, or sudden cardiac death. Among participants in the BioImage study, genetic and lifestyle factors were compared to the extent of atherosclerotic disease in the coronary arteries at baseline. Across all three prospective studies, a higher genetic risk score significantly increased the incidence of coronary events -- as much as 90 percent in those at highest risk. While known risk factors such as a family history and elevated LDL cholesterol were also associated with an elevated genetic risk score, genetic risk was the most powerful contributor to cardiac risk. Similarly, each healthy lifestyle factor reduced risk, and the unfavorable lifestyle group also had higher levels of hypertension, diabetes and other known risk factors upon entering the studies. Within each genetic risk category, the presence of lifestyle factors significantly altered the risk of coronary events to such an extent that following a favorable lifestyle could reduce the incidence of coronary events by 50 percent in those with the highest genetic risk scores. Among participants in the BioImage study, both genetic and lifestyle factors were independently associated with levels of calcium-containing plaque in the coronary arteries, and healthy lifestyle factors were associated with less extensive plaque within each genetic risk group. "Some people may feel they cannot escape a genetically determined risk for heart attack, but our findings indicate that following a healthy lifestyle can powerfully reduce genetic risk," says Kathiresan, who is director of the Cardiovascular Disease Initiative at the Broad Institute of MIT and Harvard and an associate professor of Medicine at Harvard Medical School. "Now we need to investigate whether specific lifestyle factors have stronger impacts and conduct studies in more diverse populations, since most of the participants in these studies are white." The lead authors of the NEJM paper are Amit Khera, MD, MGH Cardiology and Center for Human Genetic Research (CHGR), and Connor Emdin, DPhil, Broad Institute. Additional co-authors are Pradeep Natarajan, MD, MGH Cardiology and CHGR; Nancy Cook, PhD, Daniel Chasman, PhD, and Paul Ridker, MD, Brigham and Women's Hospital; Alexander Bick, MD, PhD, Broad Institute; Isabel Drake, PhD, Olle Melander, MD, PhD, and Marju Orho-Melander, PhD, Lund University, Malmö, Sweden; Usman Baber, MD, Roxana Mehran, MD, and Valentin Fuster, MD, PhD, Mount Sinai Medical Center; Daniel Rader, MD, University of Pennsylvania, and Eric Boerwinkle, PhD, University of Texas Health Science Center School of Public Health. Support for the study includes an American College of Cardiology - Merck Research Fellowship and a John S. Ladue Memorial Fellowship from Harvard Medical School. Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $800 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, photomedicine and transplantation biology. The MGH topped the 2015 Nature Index list of health care organizations publishing in leading scientific journals, earned the prestigious 2015 Foster G. McGaw Prize for Excellence in Community Service. In August 2016 the MGH was once again named to the Honor Roll in the U.S. News & World Report list of "America's Best Hospitals."


News Article | November 15, 2016
Site: www.sciencedaily.com

It is well known that following a healthy lifestyle -- not smoking, avoiding excess weight and getting regular exercise -- can reduce the risk of heart disease. But what about people who have inherited gene variants known to increase risk? A study led by Massachusetts General Hospital (MGH) investigators has found that, even among those at high genetic risk, following a healthy lifestyle can cut in half the probability of a heart attack or similar event. Their report is receiving early online publication in the New England Journal of Medicine to coincide with a presentation at the American Heart Association (AHA) Scientific Sessions. "The basic message of our study is that DNA is not destiny," says Sekar Kathiresan, MD, director of the Center for Human Genetic Research at Massachusetts General Hospital (MGH), senior author of the NEJM report. "Many individuals -- both physicians and members of the general public -- have looked on genetic risk as unavoidable, but for heart attack that does not appear to be the case." In order to investigate whether a healthy lifestyle can mitigate genetic risk, the multi-institutional research team analyzed genetic and clinical data from more than 55,000 participants in four large-scale studies. Three of these -- the Atherosclerosis Risk in Communities Study, the Women's Genome Health Study, and the Malmö Diet and Cancer Study -- are prospective studies that have followed participants for up to 20 years. The fourth, the BioImage Study, assessed a variety of risk factors, including the presence of atherosclerotic plaques in the coronary arteries when participants joined the study. Each participant in the current analysis was assigned a genetic risk score, based on whether they carried any of 50 gene variants that previous studies associated with elevated heart attack risk. Based on data gathered when participants entered each study, the investigators used four AHA-defined lifestyle factors -- no current smoking; lack of obesity, defined as a body mass index less than 30; physical exercise at least once a week, and a healthy dietary pattern -- to determine a lifestyle score, whether participants had a favorable (three or four healthy factors), intermediate (two factors) or unfavorable (one or no healthy factors) lifestyle. For participants in the prospective studies, the research team investigated how each individual's genetic risk score and lifestyle factors related to the incidence of heart attack, the need for procedures designed to open blocked coronary arteries, or sudden cardiac death. Among participants in the BioImage study, genetic and lifestyle factors were compared to the extent of atherosclerotic disease in the coronary arteries at baseline. Across all three prospective studies, a higher genetic risk score significantly increased the incidence of coronary events -- as much as 90 percent in those at highest risk. While known risk factors such as a family history and elevated LDL cholesterol were also associated with an elevated genetic risk score, genetic risk was the most powerful contributor to cardiac risk. Similarly, each healthy lifestyle factor reduced risk, and the unfavorable lifestyle group also had higher levels of hypertension, diabetes and other known risk factors upon entering the studies. Within each genetic risk category, the presence of lifestyle factors significantly altered the risk of coronary events to such an extent that following a favorable lifestyle could reduce the incidence of coronary events by 50 percent in those with the highest genetic risk scores. Among participants in the BioImage study, both genetic and lifestyle factors were independently associated with levels of calcium-containing plaque in the coronary arteries, and healthy lifestyle factors were associated with less extensive plaque within each genetic risk group. "Some people may feel they cannot escape a genetically determined risk for heart attack, but our findings indicate that following a healthy lifestyle can powerfully reduce genetic risk," says Kathiresan, who is director of the Cardiovascular Disease Initiative at the Broad Institute of MIT and Harvard and an associate professor of Medicine at Harvard Medical School. "Now we need to investigate whether specific lifestyle factors have stronger impacts and conduct studies in more diverse populations, since most of the participants in these studies are white."


News Article | November 15, 2016
Site: www.biosciencetechnology.com

It is well known that a healthy lifestyle — not smoking, avoiding excess weight, and getting regular exercise — can reduce the risk of heart disease. But what about people who have inherited gene variants known to increase risk? A study led by Massachusetts General Hospital (MGH) investigators has found that, even among those at high genetic risk, leading a healthy lifestyle can cut in half the probability of a heart attack or similar event. The report received early online publication in the New England Journal of Medicine to coincide with a presentation at the American Heart Association (AHA) Scientific Sessions. “The basic message of our study is that DNA is not destiny,” said senior author Sekar Kathiresan, director of the Center for Human Genetic Research at MGH and an associate professor of medicine at Harvard Medical School (HMS). “Many individuals — both physicians and members of the general public — have looked on genetic risk as unavoidable, but for heart attack that does not appear to be the case.” The multi-institutional research team analyzed genetic and clinical data from more than 55,000 participants in four large-scale studies. Three of these — the Atherosclerosis Risk in Communities Study, the Women’s Genome Health Study, and the Malmö Diet and Cancer Study — are prospective studies that have followed participants for up to 20 years. The fourth, the BioImage Study, assessed a variety of risk factors, including the presence of atherosclerotic plaques in the coronary arteries when participants joined the initiative. Each participant in the current analysis was assigned a genetic risk score, based on whether they carried any of 50 gene variants that previous studies had associated with elevated heart attack risk. Based on data gathered when participants entered each study, the investigators used four AHA-defined lifestyle factors — no current smoking; lack of obesity, defined as a body mass index less than 30; physical exercise at least once a week; and a healthy dietary pattern — to determine whether participants had a favorable (three or four healthy factors), intermediate (two), or unfavorable lifestyle score. For participants in the prospective studies, the researchers investigated how each individual’s genetic risk score and lifestyle factors related to the incidence of heart attack, the need for procedures designed to open blocked coronary arteries, or sudden cardiac death. Among participants in the BioImage study, genetic and lifestyle factors were compared to the extent of atherosclerotic disease in the coronary arteries at baseline. Across all three prospective studies, a higher genetic risk score significantly increased the incidence of coronary events — as much as 90 percent in those at highest risk. While known risk factors such as a family history and elevated LDL cholesterol were also associated with an elevated genetic risk score, genetic risk was the most powerful contributor to cardiac risk. Each healthy lifestyle factor reduced risk. The unfavorable lifestyle group also had higher levels of hypertension, diabetes, and other known risk factors upon entering the studies. Within each risk category, the presence of lifestyle factors significantly altered the risk of coronary events to such an extent that following a favorable lifestyle could reduce the incidence of coronary events by 50 percent in those with the highest genetic risk scores. Among participants in the BioImage study, both genetic and lifestyle factors were independently associated with levels of calcium-containing plaque in the coronary arteries, and healthy lifestyle factors were associated with less extensive plaque within each genetic risk group. “Some people may feel they cannot escape a genetically determined risk for heart attack, but our findings indicate that following a healthy lifestyle can powerfully reduce genetic risk,” says Kathiresan. “Now we need to investigate whether specific lifestyle factors have stronger impacts and conduct studies in more diverse populations, since most of the participants in these studies are white.”


News Article | December 15, 2016
Site: www.eurekalert.org

Considerable evidence has indicated that the drug metformin, used for more than 50 years to treat type 2 diabetes, also can prevent or slow the growth of certain cancers; but the mechanism behind its anticancer effects has been unknown. Now a team of Massachusetts General Hospital (MGH) investigators has identified a pathway that appears to underlie metformin's ability both to block the growth of human cancer cells and to extend the lifespan of the C.elegans roundworm, implying that this single genetic pathway plays an important role in a wide range of organisms. "We found that metformin reduces the traffic of molecules into and out of the nucleus - the 'information center' of the cell," says Alexander Soukas, MD, PhD, of the MGH Center for Human Genetic Research, senior author of the study in the Dec. 15 issue of Cell. "Reduced nuclear traffic translates into the ability of the drug to block cancer growth and, remarkably, is also responsible for metformin's ability to extend lifespan. By shedding new light on metformin's health-promoting effects, these results offer new potential ways that we can think about treating cancer and increasing healthy aging." Metformin's ability to lower blood glucose in patients with type 2 diabetes appears to result from the drug's effects on the liver -- reducing the organ's ability to produce glucose for release into the bloodstream. Evidence has supported the belief that this is the result of metformin's ability to block the activity of mitochondria, structures that serve as the powerhouse of the cell. But while that explanation appears to be fairly straightforward, Soukas explains, more recent information suggests the mechanism is more complex. Several studies have suggested that individuals taking metformin have a reduced risk of developing certain cancers and of dying from cancers that do develop. Current clinical trials are testing the impact of metformin on cancers of the breast, prostate and pancreas; and several research groups are working to identify its molecular targets. Soukas's team had observed that, just as it blocks the growth of cancer cells, metformin slows growth in C.elegans, suggesting that the roundworm could serve as a model for investigating the drug's effects on cancer. Their experiments found that metformin's action against cancer relies on two elements of a single genetic pathway - the nuclear pore complex, which allows the passage of molecules into and out of the nucleus, and an enzyme called ACAD10. Basically, metformin's suppression of mitochondrial activity reduces cellular energy, restricting the traffic of molecules through the nuclear pore. This shuts off an important cellular growth molecule called mTORC1, resulting in activation of ACAD10, which both slows the growth and extends the lifespan of C.elegans. In human melanoma and pancreatic cancer cells, the investigators confirmed that application of drugs in the metformin family induced ACAD10 expression, an effect that depended on the function of the nuclear pore complex. Without the complete signaling pathway - from mitochondrial suppression, through nuclear pore restriction to ACAD10 expression - cancer cells were no longer sensitive to the effects of metformin-like drugs. "Amazingly, this pathway operates identically, whether in the worm or in human cancer cells," says Soukas, who is an assistant professor of Medicine at Harvard Medical School. "Our experiments showed two very important things: if we force the nuclear pore to remain open or if we permanently shut down ACAD10, metformin can no longer block the growth of cancer cells. That suggests that the nuclear pore and ACAD10 may be manipulated in specific circumstances to prevent or even treat certain cancers." The essential contribution of ACAD10 to metformin's anticancer action is intriguing, Soukas adds, because the only published study on ACAD10 function tied a variant in the gene to the increased risk of type 2 diabetes in Pima Indians, suggesting that ACAD10 also has a role in the drug's antidiabetes action. "What ACAD10 does is a great mystery that we are greatly interested in solving," he says. "Determining exactly how ACAD10 slows cell growth will provide additional insights into novel therapeutic targets for cancer and possibly ways to manipulate the pathway to promote healthy aging." Lianfeng Wu, PhD, of the MGH Center for Human Genetic Research (CHGR) is lead author of the Cell paper. Additional co-authors are Ben Zhou, PhD, Christopher Webster, PhD, Michael Kacergis, MS, and Michael Talkowski, PhD, MGH CHGR; Noriko Oshiro-Rapley, PhD, Fan Mou, PhD, and Christopher Carr, PhD, MGH Department of Molecular Biology; Man Li, PhD and Bin Zheng, PhD, MGH Cutaneous Biology Research Center; and Joao Paulo, PhD and Steven Gygi, PhD, Harvard Medical School. Support for this study includes NIH grants R03DK098436, K08DK087941, R01DK072041, and R01CA166717, a Broad Institute SPARC Grant, and the Ellison Medical Foundation New Scholar in Aging Award. Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $800 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, photomedicine and transplantation biology. The MGH topped the 2015 Nature Index list of health care organizations publishing in leading scientific journals and earned the prestigious 2015 Foster G. McGaw Prize for Excellence in Community Service. In August 2016 the MGH was once again named to the Honor Roll in the U.S. News & World Report list of "America's Best Hospitals."


Enhorning S.,Lund University | Enhorning S.,Skåne University Hospital | Wang T.J.,Cardiology Division | Wang T.J.,Harvard University | And 18 more authors.
Circulation | Year: 2010

BACKGROUND-: Animal studies suggest that the arginine vasopressin system may play a role in glucose metabolism, but data from humans are limited. METHODS AND RESULTS-: We analyzed plasma copeptin (copeptin), a stable C-terminal fragment of the arginine vasopressin prohormone. Using baseline and longitudinal data from a Swedish population-based sample (n=4742; mean age, 58 years; 60% women) and multivariable logistic regression, we examined the association of increasing quartiles of copeptin (lowest quartile as reference) with prevalent diabetes mellitus at baseline, insulin resistance (top quartile of fasting plasma insulin among nondiabetic subjects), and incident diabetes mellitus on long-term follow-up. New-onset diabetes mellitus was ascertained through 3 national and regional registers. All models were adjusted for clinical and anthropometric risk factors, cystatin C, and C-reactive protein. In cross-sectional analyses, increasing copeptin was associated with prevalent diabetes mellitus (P=0.04) and insulin resistance (P<0.001). During 12.6 years of follow-up, 174 subjects (4%) developed new-onset diabetes mellitus. The odds of developing diabetes mellitus increased across increasing quartiles of copeptin, even after additional adjustment for baseline fasting glucose and insulin (adjusted odds ratios, 1.0, 1.37, 1.79, and 2.09; P for trend=0.004). The association with incident diabetes mellitus remained significant in analyses restricted to subjects with fasting whole blood glucose <5.4 mmol/L at baseline (adjusted odds ratios, 1.0, 1.80, 1.92, and 3.48; P=0.001). CONCLUSIONS-: Elevated copeptin predicts increased risk for diabetes mellitus independently of established clinical risk factors, including fasting glucose and insulin. These findings could have implications for risk assessment, novel antidiabetic treatments, and metabolic side effects from arginine vasopressin system modulation. © 2010 American Heart Association, Inc.


News Article | November 13, 2016
Site: www.npr.org

DNA Is Not Destiny When It Comes To Heart Risk You can't choose your parents, so you can't help it if you're born with genes that increase your risk of heart disease. But a study finds that you can reduce that risk greatly with a healthful lifestyle. Scientists have been wondering whether that's the case. To find out, one international consortium looked at data from four large studies that had isolated genetic risk factors for heart disease. They identified genetic markers that seem to put people at nearly twice the risk for heart disease. The scientists then dug further into their data to look at behavior that helps the heart, as well as at the influence of obesity. Specifically, they looked at smoking habits, obesity, diet and exercise. People who were healthy — based on at least three of those criteria — were considered, for the purposes of the study, to be following a healthful lifestyle. The scientists were pleased to discover that the benefits of those good habits were strong, even for people who carried genetic traits that raised their risk. (Healthful habits actually benefited everyone, regardless of inherited risk.) People with unlucky genes, heart-wise, but good health habits were half as likely to develop coronary artery disease as those with unlucky genes and an unhealthful lifestyle, according to the study. The New England Journal of Medicine published the results online Sunday to coincide with a presentation of the findings at the American Heart Association's scientific sessions in New Orleans. "At least for heart attack it's pretty clear that DNA is not destiny," senior author Dr. Sekar Kathiresan, who heads the Center for Human Genetic Research at Massachusetts General Hospital, told Shots. "You have pretty good control over your own health." Kathiresan and colleagues in the United States and Sweden based their conclusion on four big studies, involving more than 55,000 people. Two of those studies have been following people for more than 20 years, including the Atherosclerosis Risk in Communities study in the United States, and a similar study in Sweden. People with unlucky genes were at about twice the risk of getting heart disease as a group, the scientists found. But those with healthful habits basically cut that risk in half. Participants in the study who had an increased genetic risk and poor health habits had a 10 percent chance of having a heart attack or similar event over the course of 10 years. And those with unlucky genes and good health habits had a 5 percent chance. That 5 percent risk was within the same ballpark of many people who had a comparatively good genetic profile, Kathiresan told Shots. The genetic test of heart risk that the researchers used "is not a test that a physician can order," he said. But materials published online along with the paper identify approximately 50 gene variants that, collectively, increase a person's risk of heart disease. And if you're determined to see how you rank in terms of genetic risk relative to the general population, a test from 23 and Me does scan these genes. Alternatively, Kathiresan said, you can assume you may have inherited a risk factor for heart disease if a parent or a sibling died young as a result of heart disease. One limitation of this study, the scientists note, is that most of the participants were white, so the results may not apply to every group. Researchers hope to soon expand their research to include a more racially diverse population.


Anderson C.D.,Center for Human Genetic Research | Anderson C.D.,Massachusetts General Hospital | Anderson C.D.,Cambridge Broad Institute | Biffi A.,Massachusetts General Hospital | And 5 more authors.
Stroke | Year: 2010

Clopidogrel is one of the most commonly prescribed medications worldwide. Recent advisories from the US Food and Drug Administration have drawn attention to the possibility of personalized decision-making for people who are candidates for clopidogrel. As is the case with antihypertensives, statins, and warfarin, common genetic sequence variants can influence clopidogrel metabolism and its effect on platelet activity. These genetic variants have, in multiple studies, been associated with adverse clinical outcomes. Concurrent medication use also influences how the body handles clopidogrel. Proton pump inhibitors, widely prescribed in conjunction with clopidogrel, may blunt its effectiveness. We address implications for bedside decision-making in light of accumulated data and current Food and Drug Administration advisories and conclude that genetic testing for CYP2C19 genotype and limitation of proton pump inhibitor interactions do not yet appear to offer an opportunity to optimize treatment given the current state of knowledge. © 2010 American Heart Association, Inc.


Anderson C.D.,Center for Human Genetic Research | Charidimou A.,Massachusetts General Hospital | Charidimou A.,University College London
Neurology | Year: 2015

The MRI era has provided vascular neurologists with a number of novel imaging markers that associate with clinical outcomes in stroke and cerebrovascular disease. Examples include periventricular white mater hyperintensities, lobar and deep cerebral microbleeds, cortical superficial siderosis, and cerebral microinfarcts.1,2 Recently, MRI-visible perivascular spaces (or Virchow-Robin spaces) have been associated with both deep and lobar intracerebral hemorrhage (ICH),3 and have therefore garnered increasing attention. Although classically thought of as extensions of the subarachnoid space coursing with penetrating cerebral vessels, evolving data suggest that Virchow-Robin spaces may actually be interstitial fluid-filled cavities and not contiguous with the subarachnoid space.4 While it is not yet clear whether all MRI-visible perivascular spaces carry the same risk implications across patient populations, their frequent coexistence on MRI and spatial association with incident ICH raise the hypothesis that they represent another imaging marker of cerebral small vessel disease and may therefore provide clues regarding the initiation and progression of related clinical and imaging phenotypes. © 2015 American Academy of Neurology.

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