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Scientists re-examine data exploring connection between serotonin gene, depression, stress

For years, scientists have been trying to determine what effect a gene linked to the brain chemical serotonin may have on depression in people exposed to stress. But now, analyzing information from more than 40,000 people who have been studied over more than a decade, researchers led by a team at Washington University School of Medicine in St. Louis have found no evidence that the gene alters the impact stress has on depression.

New research findings often garner great attention. But when other scientists follow up and fail to replicate the findings? Not so much.

In fact, a recent study published in PLOS One indicates that only about half of scientific discoveries will be replicated and stand the test of time. So perhaps it shouldnt come as a surprise that new research led by Washington University School of Medicine in St. Louis shows that an influential 2003 study about the interaction of genes, environment and depression may have missed the mark.

Since its publication in Science, that original paper has been cited by other researchers more than 4,000 times, and some 100 other studies have been published about links between a serotonin-related gene, stressful life events and depression risk. It indicated that people with a particular variant of the serotonin transporter gene were not as well-equipped to deal with stressful life events and, when encountering significant stress, were more likely to develop depression.

Such conclusions were widely accepted, mainly because antidepressant drugs called selective serotonin reuptake inhibitors (SSRIs) help relieve depression for a significant percentage of clinically depressed individuals, so many researchers thought it logical that differences in a gene affecting serotonin might be linked to depression risk.

But in this new study, the Washington University researchers looked again at data from the many studies that delved into the issue since the original publication in 2003, analyzing information from more than 40,000 people, and found that the previously reported connection between the serotonin gene, depression and stress wasnt evident. The new results are published April 4 in the journal Molecular Psychiatry.

Our goal was to get everyone who had gathered data about this relationship to come together and take another look, with each research team using the same tools to analyze data the same way, said the studys first author, Robert C. Culverhouse, PhD, an assistant professor of medicine and of biostatistics. We all ran exactly the same statistical analyses, and after combining all the results, we found no evidence that this gene alters the impact stress has on depression.

Over the years, dozens of research groups had studied DNA and life experiences involving stress and depression in the more than 40,000 people revisited in this study. Some previous research indicated that those with the gene variant were more likely to develop depression when stressed, while others didnt see a connection. So for almost two decades, scientists have debated the issue, and thousands of hours of research have been conducted. By getting all these groups to work together to reanalyze the data, this study should put the questions to rest, according to the researchers.

The idea that differences in the serotonin gene could make people more prone to depression when stressed was a very reasonable hypothesis, said senior investigator Laura Jean Bierut, MD, the Alumni Endowed Professor of Psychiatry at Washington University. But when all of the groups came together and looked at the data the same way, we came to a consensus. We still know that stress is related to depression, and we know that genetics is related to depression, but we now know that this particular gene is not.

Culverhouse noted that finally, when it comes to this gene and its connection to stress and depression, the scientific method has done its job.

Experts have been arguing about this for years, he said. But ultimately the question has to be not what the experts think but what the evidence tells us. Were convinced the evidence finally has given us an answer: This serotonin gene does not have a substantial impact on depression, either directly or by modifying the relationship between stress and depression.

With this serotonin gene variant removed from the field of potential risk factors for depression, Culverhouse and Bierut said researchers now can focus on other gene-environment interactions that could influence the onset of depression.

Culverhouse, RC, et al. Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression. Molecular Psychiatry. April 4, 2017.

This work was supported by the National Institute on Drug Abuse and the National Institute of Mental Health of the National Institutes of Health (NIH), grant numbers R21 DA033827, MH089995 and R01 DA026911. Other funding provided by the Wellcome Trust and other funding agencies from countries around the world. For a complete list of funding agencies and grants, please refer to the paper.

Potential conflicts of interest involving researchers who are authors of the study also are listed at the end of the paper. Some have received consultancy/speaking fees from various pharmaceutical companies and other business interests. LJ Bierut is one of the listed inventors on US Patent 8 080 371, Markers for Addiction, covering the use of certain DNA SNPs in determining the diagnosis, prognosis and treatment of addiction.

Washington University School of Medicines 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked seventh in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Study reverses thinking on genetic links to stress, depression - Washington University School of Medicine in St. Louis

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Stunning Contemporary Gem

Dave Smoller co-founded Canopy Biosciences

Dilip Vishwanat

Canopy Biosciences, a young startup looking to accelerate the commercialization of life science medical tools and services, has exclusively licensed a gene-editing technology from Washington University in St. Louis and Johns Hopkins University.

The company, which raised$2 million from investors earlier this year, was co-founded by Dave Smoller and is led by CEO and President Edward Weinstein. Smoller and Weinstein worked together at Sigma-Aldrich before the company was sold to Merck KGaA in November 2015 for $17 billion.

Dave Smoller co-founded Canopy Biosciences

Dilip Vishwanat

Canopy looks to in-license essentially a collaboration agreement between two parties in which one company performs research and development technologies in the fields of genetic engineering and personalized medicine.

The licensed technology is called Tunr and it targets translation elongation by introducing consecutive adenosine nucleotides into a gene coding sequence of interest, according to a release.

Excerpt from:
Canopy acquires gene-editing technology license - St. Louis Business Journal

By Sheryl Ubelacker, The Canadian Press on April 3, 2017.

TORONTO Daniel Nevins-Selvadurais case had doctors at Torontos Hospital for Sick Children baffled. At age three, he had developed blood in his stool, a sign of possible hereditary inflammatory bowel disease. But testing for all the genetic mutations known to cause the condition came back negative.

As he grew older, Daniels symptoms became more diverse. He developed unusual rashes and painful lumps in his legs, as well as having an abnormally high white cell count and low platelets in his blood, pointing to an unidentified problem with his immune system.

A host of doctors at the hospital among them specialists in blood disorders, cancer, rheumatology, immunology and gastroenterology couldnt pin down the cause of the childs illness.

Nobody could give us a diagnosis, so he was passed from one specialist to another over the years and various people did various tests, said his mother, Christina Arulrajah. He showed signs of so many different diseases.

Still, Dr. Aleixo Muise, a gastroenterologist who had been seeing Daniel for his inflammatory bowel disease, or IBD, said that because of the boys wide-ranging symptoms all the doctors thought that he must have a genetic cause to his disease.

Then in 2014, a team led by Muise launched a project to explore the genetic basis of IBD, using an advanced technology for studying patients DNA. Daniels genome was among those investigated using a technique called whole-exome sequencing.

It was then that they had their eureka moment.

Testing of Daniels genome turned up a mutation never before seen. The defect was in a gene known as ARPC1B, which produces a protein the bodys cells need to change shape, move, divide and perform other vital functions.

His ARPC1B gene was expressing none of this critical protein.

ARPC1B, we know, plays a very important role in the immune system and how different cells in the body mostly found in the blood work, said Muise.

Sometimes its surprising that one defect causes such widespread different types of disease in one patient, but this one mutation explains all the problems Daniel had.

The Sick Kids team subsequently discovered two other patients who were related to each other but not to Daniel, who also had a mutation that left them with very little ARPC1B protein. Since then, about 20 children worldwide have been identified with the genetic mutation.

It gave us enough evidence to know that this was a brand new disease that hadnt been described before, said Muise.

The discovery of whats been dubbed ARPC1B syndrome is described in Mondays edition of the journal Nature Communications.

Daniel was over the moon to get a diagnosis, said his mother. When they found out what was wrong, it was a real relief.

In his mind, its all about the cure. Now that theres a diagnosis, theres now going to be a cure.

His doctors believe a bone-marrow transplant will give Daniel new blood cells including immune cells that wont carry the genetic mutation. A search is now on for an appropriate donor for the 10-year-old.

If you do a bone-marrow transplant or you replace his immune system, this should cure him of his disease, said Muise.

Daniels mother said shes still trying to get her head around the notion of a cure after watching her son deal with so many health issues since infancy, the worst of which was seeing him repeatedly in pain.

While we have never let his illness define him, and he remains a very positive and energetic boy, it was always on the back of his mind, Arulrajah said of her soccer-loving son.

She hopes a successful bone-marrow transplant will mean an end to all the medications Daniel has had to take to treat his various symptoms over the years, including long courses of a steroid that have affected his growth.

It would be absolutely fantastic.

-Follow @SherylUbelacker on Twitter.

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Toronto doctors identify new disease in children caused by defective gene - Medicine Hat News

Durham Herald Sun

Screening genome's 'dark matter' for risks Durham Herald Sun Researchers have developed a method to swiftly screen the non-coding DNA of the human genome for links to diseases that are driven by changes in gene regulation. The technique could revolutionize modern medicine's understanding of the genetically ... and more »

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Screening genome's 'dark matter' for risks - Durham Herald Sun

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Do you know someone with cancer? If so, there is a strong chance that this person has lung cancer.

Lung cancer is the leading cause of cancer-related death in the United States and is the most common cancer worldwide. About 160,000 Americans were expected to die from lung cancer in 2016, accounting for 27 percent of all cancer-related deaths.

Rose Zolondek is a student pursuing her doctorate in philosophy at the University of Toledo college of medicine and life sciences biomedical science program.

Adaeze Izuogu Enlarge

Identifying and then screening a person at high risk can reduce the likelihood of that person dying from lung cancer. Screening allows doctors to find tumors at an earlier stage when they are more responsive to treatment and potentially curable by surgical removal. About 9 million Americans are at high risk for lung cancer. Based on a large clinical trial, early screening of people at high risk reduced the risk of dying from lung cancer by 20 percent.

How do we identify who is at risk? The risk of lung cancer varies from person to person and depends on both a persons inherited genetics and on environmental exposures such as smoking, radon, asbestos, and many other toxins that can get into your lungs.

At the University of Toledo college of medicine and life sciences, formerly the Medical College of Ohio, we are investigating the differences in our risk of lung cancer by studying differences in inherited genetic code. Most of the cells in the body, including lung cells, contain chromosomes you inherited from ones parents. Each chromosome is composed of DNA building blocks in a sequence that defines an individuals unique genetic code, just like sequences of letters define a word, sequences of musical notes define a song, or sequences of symbols define a computer program.

We now know specific DNA sequences of each human genome that produce different hair and eye color. We also see differences in DNA sequences at certain genetic locations that increase the risk for human diseases such as lung cancer. For example, certain inherited DNA sequence differences can change the way cells in the lung react to environmental exposures such as tobacco smoke.

Differences in DNA sequence are called single nucleotide polymorphisms, or SNPs. Each SNP is a change in a single DNA building block, also called a nucleotide. SNPs are found every 300 nucleotides on average. This means that ones entire genome contains about 10 million SNPs total. Most SNPs do not have any effect on ones health. However, some SNPs are within DNA sequences that code for proteins and therefore can affect ones risk for a specific disease such as lung cancer.

Our research lab studies SNPs in genetic sequences that are responsible for the repair of damaged DNA. This is a very important function within ones cells. Damaged DNA, if not repaired properly, can result in a population of cells with a DNA mutation that may lead to cancer.

We now know that if certain SNPs occur in specific genetic sequences, they can inhibit DNA from being repaired properly, which increases the chance of lung cancer, especially if you smoke.

We now have machines that can rapidly sequence the entire human genome, which is 3 billion nucleotides long. Our research lab uses these machines to identify the nucleotide sequence of SNPs that are associated with increased risk for lung cancer. My research focus is based on our recent results with genes that are responsible for protecting DNA in lung cells from damage and other genes that repair damage when it occurs.

For example, we are studying genes such as glutathione peroxidase, or GPX1, that protect lung cells from certain toxic effects of cigarette smoke. We are also studying genes called TTC38 and TRMU. Very little is known about the function of TTC38, which makes it exciting to study. We know that TRMU helps to modify letters in the DNA code and SNPs in this gene are associated with deafness, but also appear to have a role in lung cancer.

Identifying the function of SNPs in these genes help us better identify high risk individuals who may have the best benefit from regular screenings in the clinic. This would increase early detection of lung cancer and allow patients to be treated earlier. Earlier treatment often means better outcomes especially for lung cancer.

We continue to increase our understanding of lung cancer risk and to fight against this devastating disease by our ongoing collaborative work with other researchers and pulmonary doctors at the University of Toledo, the Toledo Hospital, the University of Michigan, and many other centers of excellence in lung cancer research. Our research is supported by the National Institutes of Health and the George Isaac Cancer Research Fund.

Rose Zolondek is a student pursuing her doctorate of philosophy in the University of Toledo college of medicine and life sciences biomedical science program. Ms. Zolondek is doing her research in the laboratory of Dr. James Willey. For information, contact rose.zolondek@rockets.utoledo.edu or go to utoledo.edu/med/grad/biomedical.

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UT researchers map genetic code to determine cancer risk - Toledo Blade

April 2, 2017 3D chemical structure of bisphenol A. Credit: Edgar181 via Wikimedia Commons

Exposure during infancy to the common plasticizer bisphenol A (BPA) "hijacks" and reprograms genes in the liver of newborn rats, leading to nonalcoholic fatty liver disease (NAFLD) in adulthood. A new study has found how this process occurs, and researchers will present the results Saturday at ENDO 2017, the Endocrine Society's 99th annual meeting in Orlando, Fla.

NAFLD is a buildup of extra fat in liver cells that is not caused by alcohol and that can lead to cirrhosis, or scarring, of the liver. This common disease occurs more often in people with obesity, diabetes, high cholesterol or high triglycerides (blood fats).

BPA is an industrial chemical found in polycarbonate plastics, such as many food and beverage containers, and in epoxy resins that line food cans. Past studies show that BPA and many other chemicals in our environment are endocrine-disrupting chemicals that can interfere with the body's hormones and eventually lead to obesity and other diseases.

"We believe this disease risk occurs via developmental reprogramming of the epigenome, which can persist throughout a lifetime," said the study's lead investigator, Lindsey Trevio, Ph.D., an instructor and researcher at Baylor College of Medicine, Houston, Texas. "These persistent changes lead to alterations in gene expression in ways that correlate with increased disease susceptibility."

In both rats and humans, the epigenome programs our complete set of DNA (the genome), but unlike genetic defects, epigenomic reprogramming can be reversed, Trevio said.

"Understanding the mechanisms underlying this endocrine disruptor-mediated epigenomic reprogramming may lead to the identification of biomarkers for people at risk as well as possible interventions and therapeutics for NAFLD," she said.

In research funded by the National Institute of Environmental Health Sciences, Trevio and her colleagues sought to identify the molecular causes of the developmental reprogramming they had observed in past animal studies. They treated newborn rats with low, environmentally relevant doses of BPA during a critical period of liver development: the five days after birth. The liver, she explained, is "a central player in fat metabolism and obesity." Then they examined liver tissue from the BPA-exposed rats immediately after exposure or when the rats were adults. These tissue samples were compared with liver samples from control rats who did not receive BPA.

Trevio reported that BPA-exposed rats, but not control rats, that were fed a high-fat diet as adults had increased liver weight and raised levels of total cholesterol, "bad" (LDL) cholesterol and triglycerides. Furthermore, genes involved in the progression of NAFLD exhibited increased expression in the liver of the BPA-exposed rats, but not in control animals. Specifically, she said they found that BPA created two new activating epigenomic marks on genes driving progression of NAFLD. These marks appear at key regulatory regions of affected genes, thus likely becoming "super promoters" that code the gene to turn on. However, she noted that this change appears to require a later-in-life challenge, such as eating a high-fat diet.

The researchers have reportedly seen BPA and other endocrine disruptors promoting epigenomic reprogramming in additional tissues in rats. Trevio said, "Our findings could be useful in other diseases as well. Because these endocrine disruptors are ubiquitous in the environment, a large portion of the population may be affected by developmental reprogramming."

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Early-life BPA exposure reprograms gene expression linked to fatty liver disease - Medical Xpress

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One family with rare gene mutation gives clues to preventing heart attacks

Patients with mutations that disable a gene called ANGPTL3 have extremely low levels of cholesterol in the bloodstream. They also show no evidence of plaque in the coronary arteries, suggesting the mutations protect against heart attacks. Studying such patients can help guide drug development with the goal of preventing heart attacks.

Natural genetic changes can put some people at high risk of certain conditions, such as breast cancer, Alzheimers disease or high blood pressure. But in rare cases, genetic errors also can have the opposite effect, protecting individuals with these helpful genetic mistakes from developing common diseases.

A new study of such beneficial genetic mutations, led by Washington University School of Medicine in St. Louis, may provide guidance on the design of new therapies intended to reduce the risk of heart attacks.

The study is published March 29 in the Journal of the American College of Cardiology.

The researchers studied members of a family with rare mutations in a gene called ANGPTL3. The gene is known to play important roles in processing lipoproteins, molecules that package and transport fat and cholesterol through the bloodstream. Partial or complete loss of this gene was known to cause low cholesterol and triglyceride levels in the bloodstream. But whether it affects risk of heart attack was unclear.

Three of these family members those with a complete loss of this gene showed extremely low blood cholesterol and no evidence of plaque in their coronary arteries. According to the study authors, it was noteworthy that one of these patients showed no evidence of atherosclerosis despite having high risk factors for it, including high blood pressure and a history of type 2 diabetes and tobacco use.

The family members with complete loss of ANGPTL3 have extraordinarily low cholesterol, said first author Nathan O. Stitziel, MD, PhD, an assistant professor of medicine and of genetics. The interesting thing about this family is the individuals with total loss of this gene had siblings with normal copies of the same gene. So we could compare people with differences in the function of this gene who are otherwise closely related genetically and share similar environments. Its an anecdotal study of one family, but we felt it might provide some insight into the effects of blocking ANGPTL3.

While the individuals with nonfunctional copies of the gene showed no coronary plaque, their siblings with working copies of the gene showed evidence of plaque in the coronary arteries, though it was not yet causing symptoms a situation that is common in the general population, according to Stitziel.

To study the gene beyond the experience of a single family, the scientists also analyzed data available from large population studies. In data from one study of about 20,000 patients, the researchers found those with a partial loss of this gene had, on average, 11 percent lower total cholesterol, 12 percent lower LDL cholesterol, and 17 percent lower triglycerides, measured in the blood, than individuals with full gene function.

Analysis of data from other large population studies showed a link between partial loss of the gene and a lower risk of coronary artery disease and an association between lower circulating levels of ANGPTL3 protein and a lower risk of heart attack.

Taken together, these findings provide support for efforts to develop drugs that inhibit ANGPTL3 in order to reduce the risk of coronary artery disease and heart attack. The same reasoning led to the development of a class of drugs known as PCSK9 inhibitors, which have recently been shown to be effective at reducing the risk of heart attack in a large clinical trial of more than 27,000 men and women.

Several years ago, researchers found natural beneficial mutations in the PCSK9 gene that lowered peoples cholesterol levels and protected them from coronary artery disease, much as mutations in ANGPTL3 seem to do. Both PCSK9 and ANGPTL3 are important in the bodys processing of cholesterol from the diet. Any drugs that inhibit them, then, work differently than commonly prescribed statins, which reduce cholesterol levels in the blood by blocking the bodys internal cholesterol manufacturing.

While reducing cholesterol levels in the blood typically is thought to be good for the heart, Stitziel pointed out that there may be dangers to inhibiting the normal function of a gene. Not all genetic mutations that result in low cholesterol in the bloodstream are healthy. For example, there is one genetic disorder in which cholesterol levels in the blood are low because cholesterol gets stuck in the liver, resulting in fatty liver disease.

We need a better understanding of how cholesterol is processed in individuals with complete loss of ANGPTL3 function before we can fully say what effect inhibiting ANGPTL3 is going to have, Stitziel said. Studies of people with mutations that completely knock out a genes function are important because they can provide insight into the potential effects both good and bad of drugs inhibiting that genes function.

Along with Washington University School of Medicine, other institutions that played key roles in the study included the Broad Institute of MIT and Harvard and the Perelman School of Medicine at the University of Pennsylvania.

This study was supported by the National Institutes of Health (NIH), grant numbers R01HL131961, K08HL114642, R01HL118744, R01HL127564, R21HL120781, U54HG003067, UM1HG008895, UM1HG008853, TR001100, T32HL007734, RC2HL101834 and RC1TW008485; the Barnes-Jewish Hospital Foundation; the Fannie Cox Prize for Excellence in Science Teaching, Harvard University; a MGH Research Scholar Award; an ACCF/Merck Cardiovascular Research Fellowship; a John S. Ladue Memorial Fellowship at Harvard Medical School; the BHF and NIHR Senior Investigator support; and Fogarty International, grant number RC1TW008485.

The authors report grant funding or consulting fees from AstraZeneca, Aegerion Pharmaceuticals, Merck, Amarin, Alnylam Pharmaceuticals, Eli Lilly and Company, Pfizer, Sanofi, Novartis, Regeneron, Genentech, Bayer Healthcare, Leerink Partners, Noble Insights, Quest Diagnostics and Genomics PLC. One author, Rader, reports being an inventor on a patent related to lomitapide that is owned by the University of Pennsylvania and licensed to Aegerion Pharmaceuticals. He also reports co-founding Vascular Strategies and Staten Biotechnology. Another author, Kathiresan, reports holding equity in San Therapeutics and Catabasis Pharmaceuticals.

Stitziel NO, Khera AV, Wang X, Bierhals JB, Vourakis C, Sperry AE, Natarajan P, Klarin D, Emdin CA, Zekavat SM, Nomura A, Erdman J, Schunkert H, Samani NJ, Kraus WE, Shah SH, Yu B, Boerwinkle E, Rader DJ, Gupta N, Frossard PM, Rasheed A, Danesh J, Lander ES, Gabriel S, Saleheen D, Musunuru K, Kathiresan S, PROMIS and Myocardial Infarction Genetics Consortium Investigators. ANGPTL3 deficiency and protection against coronary artery disease. Journal of the American College of Cardiology. March 29, 2017.

Washington University School of Medicines 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked seventh in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Genetic errors associated with heart health may guide drug development - Washington University School of Medicine in St. Louis

By Doris T. Zallen | Zallen is professor emerita of science studies and humanities at Virginia Tech. She is the author of To Test or Not to Test: A Guide to Genetic Screening and Risk.

The Preserving Employee Wellness Programs Act (HR 1313), now being pushed by Republicans in the House of Representatives, is a threat to employees, will not improve wellness programs, and has the potential to unleash a corrosive force that could undermine the future of genomic medicine.

Genetic testing is becoming a central tool in the 21st century medical arsenal. Advances in genetics first made it possible to identify specific genes that bring on specific, relatively rare, health conditions such as cystic fibrosis, sickle-cell disease and muscular dystrophy.

Recent advances have yielded genetic tests that can identify people who, though healthy now, are at a higher-than-average risk for developing an illness in the future. Examples here include breast cancer, Parkinsons disease and Alzheimers disease all quite common.

However, these risk-raising genes are imperfect predictors. Environmental factors, including diet and exercise, also play key roles. The reality is that being found to have a risk-raising gene does not mean you will get the disease and, because of the involvement of environmental factors, you can get the disease without having the gene.

HR 1313 would allow employers to require genetic testing of employees in their wellness programs and assess harsh financial penalties on those who refuse. This is bad news. There are perfectly good reasons for people to decide to not have genetic testing for particular genes. Many people, learning of a higher risk for developing a future illness, suffer severe emotional distress, especially when there are no effective treatments or known cures to ward them off.

James Watson, Nobel laureate for the discovery of the structure of DNA, had his entire genome sequenced and made available online to aid in genetic research. But, he insisted that information about one of his own genes, the APOE gene, not be revealed. One form of the APOE gene is a known risk factor for late-onset Alzheimers. He did not want the burden of knowing.

Nancy Wexler, whose pioneering research led to the development of the genetic test for Huntington Disease a disease that runs in her own family decided against having that very test. For her, living with the uncertainty about her own genetic status is better than knowing for sure. Because genes are shared within families, a genetic test of one person is also a test of a whole family. Some relatives want to know; others do not.

Research has shown that genetic information spreading through families, often without any proper explanation, can bring on discord and deep divisions fueled by anger and guilt. And then, there is also the sad history of the misuse of genetic information, particularly the debacle of eugenics policies practiced widely in the U.S. during the first half of the last century. An abundance of prejudice, coupled with baseless beliefs about inheritance, led to Americans being forcibly sterilized for supposedly having sub-par genes.

More than 60,000 people, typically poor and uneducated, were victims of these policies. Sadly, eugenic policies were vigorously pursued in this part of Virginia. There are real concerns that HR 1313 can usher in a new era of eugenics an era in which employers, under the guise of improving health, are able to use genetic information to weed out those who may develop health conditions that could interfere with their productivity at some point in the future.

Existing legislation, the Genetic Non-Discrimination Act of 2008 (or GINA), has restricted the use of genetic information in the workplace. These protections will evaporate if HR 1313 becomes law. Genetic testing needs to remain an individual decision a decision determined by ones own values, life experience, family realities and attitudes about privacy. People should decide on their own what, if any, genetic tests they want and follow up with their own doctors to determine a course of action once the results are received.

Wellness programs can continue to help their clients achieve better health through smoking cessation, better diets, more exercise, and the like without any need for requiring genetic testing. If such testing is inflicted on people, then genetic information may well become viewed as a mode of punishment something to be feared instead of the valuable adjunct to the personalized medical care that is the promise of genomic medicine.

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Zallen: Genetic testing bill is modern eugenics - Roanoke Times

March 30, 2017 by Julia Evangelou Strait Credit: Washington University School of Medicine

Natural genetic changes can put some people at high risk of certain conditions, such as breast cancer, Alzheimer's disease or high blood pressure. But in rare cases, genetic errors also can have the opposite effect, protecting individuals with these helpful genetic mistakes from developing common diseases.

A new study of such "beneficial" genetic mutations, led by Washington University School of Medicine in St. Louis, may provide guidance on the design of new therapies intended to reduce the risk of heart attacks.

The study is published March 29 in the Journal of the American College of Cardiology.

The researchers studied members of a family with rare mutations in a gene called ANGPTL3. The gene is known to play important roles in processing lipoproteins, molecules that package and transport fat and cholesterol through the bloodstream. Partial or complete loss of this gene was known to cause low cholesterol and triglyceride levels in the bloodstream. But whether it affects risk of heart attack was unclear.

Three of these family membersthose with a complete loss of this geneshowed extremely low blood cholesterol and no evidence of plaque in their coronary arteries. According to the study authors, it was noteworthy that one of these patients showed no evidence of atherosclerosis despite having high risk factors for it, including high blood pressure and a history of type 2 diabetes and tobacco use.

"The family members with complete loss of ANGPTL3 have extraordinarily low cholesterol," said first author Nathan O. Stitziel, MD, PhD, an assistant professor of medicine and of genetics. "The interesting thing about this family is the individuals with total loss of this gene had siblings with normal copies of the same gene. So we could compare people with differences in the function of this gene who are otherwise closely related genetically and share similar environments. It's an anecdotal study of one family, but we felt it might provide some insight into the effects of blocking ANGPTL3."

While the individuals with nonfunctional copies of the gene showed no coronary plaque, their siblings with working copies of the gene showed evidence of plaque in the coronary arteries, though it was not yet causing symptomsa situation that is common in the general population, according to Stitziel.

To study the gene beyond the experience of a single family, the scientists also analyzed data available from large population studies. In data from one study of about 20,000 patients, the researchers found those with a partial loss of this gene had, on average, 11 percent lower total cholesterol, 12 percent lower LDL cholesterol, and 17 percent lower triglycerides, measured in the blood, than individuals with full gene function.

Analysis of data from other large population studies showed a link between partial loss of the gene and a lower risk of coronary artery disease and an association between lower circulating levels of ANGPTL3 protein and a lower risk of heart attack.

Taken together, these findings provide support for efforts to develop drugs that inhibit ANGPTL3 in order to reduce the risk of coronary artery disease and heart attack. The same reasoning led to the development of a class of drugs known as PCSK9 inhibitors, which have recently been shown to be effective at reducing the risk of heart attack in a large clinical trial of more than 27,000 men and women.

Several years ago, researchers found natural beneficial mutations in the PCSK9 gene that lowered people's cholesterol levels and protected them from coronary artery disease, much as mutations in ANGPTL3 seem to do. Both PCSK9 and ANGPTL3 are important in the body's processing of cholesterol from the diet. Any drugs that inhibit them, then, work differently than commonly prescribed statins, which reduce cholesterol levels in the blood by blocking the body's internal cholesterol manufacturing.

While reducing cholesterol levels in the blood typically is thought to be good for the heart, Stitziel pointed out that there may be dangers to inhibiting the normal function of a gene. Not all genetic mutations that result in low cholesterol in the bloodstream are healthy. For example, there is one genetic disorder in which cholesterol levels in the blood are low because cholesterol gets stuck in the liver, resulting in fatty liver disease.

"We need a better understanding of how cholesterol is processed in individuals with complete loss of ANGPTL3 function before we can fully say what effect inhibiting ANGPTL3 is going to have," Stitziel said. "Studies of people with mutations that completely knock out a gene's function are important because they can provide insight into the potential effectsboth good and badof drugs inhibiting that gene's function."

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Genetic errors associated with heart health may guide drug development - Medical Xpress