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I like to know what percentage of genetic disease are preventable before birth?
Also, when we can detect all of them? I heard in a TV show a doctor said about 5 years later we can prevent all genetic disease! Is this estimation true?
There is no simple answer to either of your questions.
There are many monogenic diseases where mutations in single genes result in disease phenotype.
There are far more diseases that have a genetic component where mutations in one or more gene increase the baseline risk of disease and this risk is then modified by the environment the individual encounters throughout their life-time (see Multiple Genes).
To get an overview of the functions of genes that have been so far identified, mutations within them and the diseases they have been linked to see Online Mendelian Inheritance in Man (OMIM).
If you want to get a feel for just how complex genetics is then a recently published paper on the genetics of hair colour would be worth reading…
Genome-wide study of hair colour in UK Biobank explains most of the SNP heritability
I like to know what percentage of genetic disease are preventable before birth?
Essentially 0%. There have been a few experimental applications of gene thereapy, but we're talking about a few thousand of people in the entire world. None are available in the context of ordinary medical care. Some genetic diseases can treated after birth with drugs that moderate the worst effects: haemophilia, PKU, and cystic fibrosis for example, but the underlying genetic problem remains.
Race and health
Race and health refers to how being identified with a specific race influences health. Race is a complex concept that has changed across chronological eras and depends on both self-identification and social recognition.  In the study of race and health, scientists organize people in racial categories depending on different factors such as: phenotype, ancestry, social identity, genetic makeup and lived experience. “Race” and ethnicity often remain undifferentiated in health research.  
Differences in health status, health outcomes, life expectancy, and many other indicators of health in different racial and ethnic groups are well documented.  Epidemiological data indicate that racial groups are unequally affected by diseases, in terms or morbidity and mortality.  Some individuals in certain racial groups receive less care, have less access to resources, and live shorter lives in general.  Overall, racial health disparities appear to be rooted in social disadvantages associated with race such as implicit stereotyping and average differences in socioeconomic status.   
Health disparities are defined as “preventable differences in the burden of disease, injury, violence, or opportunities to achieve optimal health that are experienced by socially disadvantaged populations”.  According to the U.S. Centers for Disease Control and Prevention, they are intrinsically related to the “historical and current unequal distribution of social, political, economic and environmental resources".  
The relationship between race and health has been studied from multidisciplinary perspectives, with increasing focus on how racism influences health disparities, and how environmental and physiological factors respond to one another and to genetics.  
Eye Disease: Inherited & Genetic
Genetic factors play a role in many kinds of eye disease, including those diseases that are the leading cause of blindness among infants, children and adults.
More than 60 percent of cases of blindness among infants are caused by inherited eye diseases such as congenital (present at birth) cataracts, congenital glaucoma, retinal degeneration, optic atrophy and eye malformations. Up to 40% of patients with certain types of strabismus (ocular misalignment) have a family history of the disease and efforts are currently under way to identify the responsible genes.
In adults, glaucoma and age-related macular degeneration are two of the leading causes of blindness, and both appear to be inherited in a large portion of cases. Researchers have mapped several genes for glaucoma and are starting to identify genes involved in macular degeneration. They also are making very significant progress in identifying the genes that cause retinitis pigmentosa, a degenerative disease of the retina that causes night blindness and gradual vision loss.
Can common vision problems be inherited?
Genetics also play a role in vision problems that occur in otherwise healthy eyes. Genetic ophthalmologic researchers now have evidence that the most common vision problems among children and adults are genetically determined. The list includes strabismus (cross-eyes), amblyopia (lazy eye) and refraction errors such as myopia (nearsightedness), hyperopia (farsightedness) and astigmatism.
Can eye abnormalities be caused by other diseases?
Eye abnormalities are present in one-third of inherited, systemic diseases. The presence of a particular ocular sign known to be associated with a systemic disease often is the deciding factor in confirming the diagnosis of that disease. For example, a dislocated lens in the eye can confirm a diagnosis of Marfan syndrome, a connective tissue disease associated with heart problems a characteristic cherry red spot in the eye usually indicates Tay-Sachs disease.
Can inherited eye diseases be corrected if an early diagnosis is made?
Physicians in the Center for Genetic Eye Diseases at the Cole Eye Institute work closely with specialists in the Medical Genetics Program and other services at the Cleveland Clinic to provide early diagnosis and effective treatment for complications of inherited eye disorders. They also provide evaluation and treatment for patients referred to the Center from community physicians.
Your ophthalmologist, pediatrician, geneticist or family doctor may refer you or your child to the Center for specialized evaluation, testing and diagnosis if a genetic eye disease is suspected. The Cole Eye Institute and the Center for Genetic Eye Diseases are part of the world-class Cleveland Clinic, which includes more than 750 physicians practicing in more than 100 specialties. For patients with systemic genetic diseases, Cole Eye Institute specialists work closely with experts in other areas to integrate ophthalmologic treatment into the patient's total care plan.
What can I expect during an evaluation?
When you or your child is referred to the Center, a genetic eye disease specialist will work with you to diagnose the problem and plan follow-up and possible therapy.
The first step is a complete review of any medical records or test results available, whether performed at the Cleveland Clinic or at another institution. Next, you will be asked about your personal and family medical history, with particular attention given to signs and symptoms of genetic disorders. After this is complete, you will be asked to assist in drawing your family tree and identifying other family members who may be affected with similar problems. Patients undergo a comprehensive assessment of vision and eye movement, a slit-lamp examination for microscopic study of the eye, and an eye-pressure check. By using eye drops to dilate the pupils, the ophthalmologist can examine the lens, optic nerve and retina for abnormalities.
Using information from the eye examination and the general medical history and examination, the ophthalmologist and the referring physician together determine a diagnosis and treatment plan.
Center ophthalmologists have the expertise to diagnose and offer advice on the treatment of genetic eye diseases. When additional expertise in specific eye problems is required, they call on other Cleveland Clinic Cole Eye Institute specialists for a second opinion or consultation.
CLINICAL ASPECTS OF NICOTINE ADDICTION
PSYCHOACTIVE EFFECTS OF NICOTINE
Nicotine induces pleasure and reduces stress and anxiety. Smokers use it to modulate levels of arousal and to control mood. Smoking improves concentration, reaction time, and performance of certain tasks. Relief from withdrawal symptoms is probably the primary reason for this enhanced performance and heightened mood. 31 Cessation of smoking causes the emergence of withdrawal symptoms: irritability, depressed mood, restlessness, and anxiety. 32 The intensity of these mood disturbances is similar to that found in psychiatric outpatients. 33 Anhedonia — the feeling that there is little pleasure in life — can also occur with withdrawal from nicotine, and from other drugs of abuse. 34
The basis of nicotine addiction is a combination of positive reinforcements, including enhancement of mood and avoidance of withdrawal symptoms ( Fig. 3 ). 35 In addition, conditioning has an important role in the development of tobacco addiction.
Craving — induced by smoking cues, stressors, or a desire to relieve withdrawal symptoms — triggers the act of smoking a cigarette, which delivers a spike of nicotine to the brain. Nicotinic cholinergic receptors (nAChRs) are activated, resulting in the release of dopamine and other neurotransmitters, which in turn cause pleasure, stimulation, and mood modulation. Receptor activation also results in the development of new neural circuits (neural plasticity) and, in association with environmental cues, behavioral conditioning. After being activated by nicotine, nAChRs ultimately become desensitized to it, which results in short-term tolerance of nicotine and reduced satisfaction from smoking. In the time between smoking cigarettes, or after quitting tobacco use, brain nicotine levels decline, which leads to reduced levels of dopamine and other neurotransmitters and to withdrawal symptoms, including craving. In the absence of nicotine, nAChRs regain their sensitivity to nicotine and become reactivated in response to a new dose. Adapted from Dani and Heinemann. 35
When a person who is addicted to nicotine stops smoking, the urge to resume is recurrent and persists long after withdrawal symptoms dissipate. With regular smoking, the smoker comes to associate specific moods, situations, or environmental factors — smoking-related cues — with the rewarding effects of nicotine. Typically, these cues trigger relapse.
The association between such cues and the anticipated effects of nicotine, and the resulting urge to use nicotine, constitute a form of conditioning. Studies in animals show that nicotine exposure causes changes in the protein expression of brain cells and in their synaptic connections — a process termed neural plasticity — which underlie conditioning. 36 , 37 Nicotine also enhances behavioral responses to conditioned stimuli, which may contribute to compulsive smoking. 38 Furthermore, studies in nicotine-dependent rats show that conditioned stimuli associated with nicotine withdrawal increase the magnitude of withdrawal through an elevation of the brain’s reward threshold. 39 Thus, cues associated with nicotine withdrawal can decrease the function of the brain’s reward systems.
The desire to smoke is maintained, in part, by such conditioning. Smokers usually take a cigarette after a meal, with a cup of coffee or an alcoholic drink, or with friends who smoke. When repeated many times, such situations become a powerful cue for the urge to smoke. Aspects of smoking itself — the manipulation of smoking materials, or the taste, smell, or feel of smoke in the throat — also become associated with the pleasurable effects of smoking. 40 , 41 Even unpleasant moods can become conditioned cues for smoking: a smoker may learn that not having a cigarette provokes irritability and that smoking one provides relief. After repeated experiences like this, a smoker can sense irritability from any source as a cue for smoking. Functional imaging studies have shown that exposure to drug-associated cues activates cortical regions of the brain, including the insula (a structure in the cortex associated with certain basic emotions). Smokers who sustain damage to the insula (e.g., brain trauma) are more likely to quit smoking soon after the injury, and to remain abstinent, and are less likely to have conscious urges to smoke than smokers with brain injury that does not affect the insula. 42
THE TOBACCO ADDICTION CYCLE
Smoking is a highly efficient form of drug administration. Inhaled nicotine enters the circulation rapidly through the lungs and moves into the brain within seconds. Rapid rates of absorption and entry into the brain cause a strongly felt “rush” and reinforce the effects of the drug. In animals, rapid administration of nicotine potentiates locomotor sensitization, which is linked to reward, and neuroplastic changes in the brain. 43 The smoking process also provides rapid reinforcement and allows for precise dosing, making it possible for a smoker to obtain desired effects without toxicity. Unlike cigarettes, nicotine medications marketed to promote smoking cessation deliver nicotine slowly, and the risk of abuse is low. 44 In addition to delivering nicotine to the brain quickly, cigarettes have been designed with additives and engineering features to enhance its addictiveness. 45
There is considerable peak-to-trough oscillation in blood levels of nicotine from cigarette to cigarette. Nevertheless, it accumulates in the body over the course of 6 to 9 hours of regular smoking and results in 24 hours of exposure. Arteriovenous differences in nicotine concentrations during cigarette smoking are substantial, with arterial levels up to 10 times as high as venous levels. 46 The persistence of nicotine in the brain throughout the day and night changes the structure and function of nicotinic receptors, stimulating intracellular processes of neuroadaptation.
The pharmacologic basis of nicotine addiction is thus a combination of positive reinforcements, such as enhancement of mood and mental or physical functioning, and avoidance of withdrawal symptoms when nicotine is not available. Figure 4 shows a typical daily smoking cycle. 47
The first cigarette of the day has a substantial pharmacologic effect, primarily arousal, but at the same time, tolerance to nicotine begins to develop. A second cigarette is smoked later, at a time when the smoker has learned that there is some regression of tolerance. With subsequent smoking, there is an accumulation of nicotine in the body, resulting in a greater level of tolerance, and withdrawal symptoms become more pronounced between successive cigarettes. The shaded area of the graph represents the affective neutral zone that exists between the threshold level of nicotine needed to produce pleasure and arousal and the threshold level below which withdrawal symptoms will occur. Transiently high levels of nicotine in the brain after individual cigarettes are smoked may partially overcome tolerance, but the primary (euphoric) effects of nicotine tend to lessen throughout the day. Abstinence overnight allows considerable resensitization to the actions of nicotine. Adapted from Benowitz. 47
Smokers tend to take in the same amount of nicotine from day to day to achieve the desired effects. They adjust their smoking behavior to compensate for changes in the availability of nicotine (e.g., when switching from regular to low-yield cigarettes) to regulate the body’s level of nicotine. 48 Light smokers (those who smoke 𢙅 cigarettes per day) and occasional smokers smoke primarily for the positive reinforcing effects of nicotine and have minimal or no withdrawal symptoms. 49 They smoke primarily in association with particular activities (after eating a meal or while drinking alcohol), and are less likely to smoke in response to negative affect. Although withdrawal symptoms may not be prominent, many light and occasional smokers have difficulty quitting. Some of them have a high level of dependence, but with pharmacodynamics that differ from those in heavier smokers.
CDC Prevention Programs
An estimated 80% of cardiovascular disease, including heart disease and stroke, are preventable. However, cardiovascular disease remains the No. 1 killer and the most expensive disease, costly nearly $1 billion a day. While cardiovascular disease is largely preventable, it tops the disease burden list and this situation is expected to worsen according to recent projections showing that by 2035, 45% of the U.S. adult population will live with cardiovascular disease at an annual cost of more than $1 trillion. Yet effective Centers for Disease and Control and Prevention (CDC) evidence-based programs are not fully implemented due to limited congressional resources. Congress can help stem the effect of cardiovascular disease and make the U.S. a healthier place to live by ensuring that each state has sufficient resources to implement tailored programs to help prevent and control this costly, disabling and deadly disease.
The American Heart Association advocates for robust funding for CDC&rsquos Heart Disease and Stroke Prevention Programs, including heart disease and stroke prevention, Million Hearts 2022, and WISEWOMAN.
CDC supports heart disease and stroke prevention in all 50 states, and the District of Columbia. These programs work to prevent, manage and reduce heart disease and stroke, with an emphasis on cutting risk factors and reducing health disparities within State, local, and Tribal public health departments and boost surveillance and implementation research.
A public-private initiative, Million Hearts 2022 works to prevent 1 million heart attacks strokes over five years through the continued implementation of the ABCS (aspirin as appropriate, blood pressure control, cholesterol management, and smoking cessation), development of innovative, scalable ways to communities and the healthcare sector to execute evidence-based prevention in the highest burden areas and to expand focus on physical activity, cardiac rehabilitation, and people age 35-64 whose event rates are on the rise.
The Well-Integrated Screening and Evaluation for Women Across the Nation (WISEWOMAN) program helps uninsured and under-insured low-income women ages 40 to 64 understand and reduce their risk for heart disease and stroke by providing risk factor screenings and connecting them with lifestyle programs, health counseling and other community resources that promote lasting, healthy behavior change.
Written by American Heart Association editorial staff and reviewed by science and medicine advisers. See our editorial policies and staff.
Medical Definition of Genetic disease
Genetic disease: A disease caused by an abnormality in an individual's genome.
There are a number of different types of genetic inheritance:
- Single gene inheritance -- Also called Mendelian or monogenic inheritance. This type of inheritance is caused by changes or mutations that occur in the DNA sequence of a single gene. There are more than 6,000 known single-gene disorders, which occur in about 1 out of every 200 births. Some examples are cystic fibrosis, sickle cell anemia, Marfan syndrome, Huntington's disease, and hemochromatosis. Single-gene disorders are inherited in recognizable patterns: autosomal dominant, autosomal recessive, and X-linked.
- Multifactorial inheritance -- Also called complex or polygenic inheritance. This type of inheritance is caused by a combination of environmental factors and mutations in multiple genes. For example, different genes that influence breast cancer susceptibility have been found on chromosomes 6, 11, 13, 14, 15, 17, and 22. Some common chronic diseases are multifactorial disorders. Examples include heart disease, high blood pressure, Alzheimer disease, arthritis, diabetes, cancer, and obesity. Multifactorial inheritance also is associated with heritable traits such as fingerprint patterns, height, eye color, and skin color.
- Chromosome abnormalities -- Chromosomes, distinct structures made up of DNA and protein, are located in the nucleus of each cell. Because chromosomes are the carriers of the genetic material, abnormalities in chromosome number or structure can result in disease. For example, Down syndrome or trisomy 21 is a common disorder that occurs when a person has three copies of chromosome 21. There are many other chromosome abnormalities including Turner syndrome (45,X), Klinefelter syndrome (47, XXY), the cat cry syndrome (46, XX or XY, 5p-), and so on.
- Mitochondrial inheritance -- This type of genetic disorder is caused by mutations in the nonchromosomal DNA of mitochondria. Mitochondria are small round or rod-like organelles that are involved in cellular respiration and found in the cytoplasm of plant and animal cells. Each mitochondrion may contain 5 to 10 circular pieces of DNA. Examples of mitochondrial disease include an eye disease called Leber's hereditary optic atrophy a type of epilepsy called MERRF which stands for Myoclonus Epilepsy with Ragged Red Fibers and a form of dementia called MELAS for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes.
The sequence of the human genome provides the first holistic view of our genetic heritage. While not yet complete, continued refinement of the data bring us ever closer to a complete human genome reference sequence. The 46 human chromosomes (22 pairs of autosomal chromosomes and 2 sex chromosomes) between them house almost 3 billion base pairs of DNA that contains about 30 to 40,000 protein-coding genes. The coding regions make up less than 5% of the genome (the function of the remaining DNA is not clear) and some chromosomes have a higher density of genes than others.
Most genetic diseases are the direct result of a mutation in one gene. However, one of the most difficult problems ahead is to find out how genes contribute to diseases that have a complex pattern of inheritance, such as in the cases of diabetes, asthma, cancer and mental illness. In all these cases, no one gene has the yes/no power to say whether a person has a disease or not. It is likely that more than one mutation is required before the disease is manifest, and a number of genes may each make a subtle contribution to a person's susceptibility to a disease genes may also affect how a person reacts to environmental factors.
What percent of genetic disease are preventable? - Biology
There are over 6,000 genetic disorders that can be passed down through the generations, many of which are fatal or severely debilitating. Since 1997, the GDF has worked with Mount Sinai to help provide funding for research to improve early detection and treatment options for many of these disorders.
See some of the most notable ways in which GDF and its supporters have made an impact over the past year in advancing our mission to help prevent, manage and treat inherited genetic diseases. View our latest News Brief here. You can sign up to receive regular news and updates from GDF at the top of this page.
The GDF has partnered with the Department of Genetics and Genomic Sciences at Mount Sinai in New York City, one of the largest medical genetics centers in the world. Recognized as a leader in its field, it has more than 50 internationally recognized physician and scientist faculty members and has made numerous contributions to the diagnosis, prevention and treatment of genetic diseases. Learn how advances at Mount Sinai have impacted the lives of thousands of people and provide hope for the future.
Being diagnosed with a genetic disease can be extremely difficult and confusing for you and your family. If you or a loved one has been diagnosed recently, the GDF may be able to help you navigate through this complicated time. Through our affiliation with Mount Sinai’s Department of Genetics and Genomic Sciences, we can help connect you with world-class physicians and genetic counselors in specific disease groups. Learn more on our newly diagnosed patient resource page.
Your support can lead to remarkable gene discoveries and treatments that fight against genetic diseases.
Learn how the GDF has used its fundraising efforts to help further research programs at Mount Sinai.
Gaucher Disease is the most common of the lipid storage diseases. Learn about its symptoms, how it is inherited and available treatments.
The National Organization for Rare Disorders (NORD) is an invaluable resource for people with rare "orphan" diseases. View NORD news and events.
From Michigan Medicine at the University of Michigan
The gift will go to support the breast health fellowships in obstetrics and gynecology.
This year’s Miles for Mia Memorial 5K Walk/Run was another big success in support of genetic disease research and education.
What consumer DNA data can and can’t tell you about your risk for certain diseases
RISKS AND RIDDLES Now that Lara Diamond has been through a cancer diagnosis, she advises others on how to deal with the personal health information uncovered in genetic testing.
Results from Family Tree DNA, a genetic testing company, helped Lara Diamond find a branch of her family she thought had been lost in the Holocaust. Those 2012 results brought dozens of new people into her life.
Eager to find more relatives, Diamond, now 42, a professional genealogist in Baltimore, decided to try out all the companies that offer geneaological DNA testing to see what else she could learn. Results from one of them, 23andMe, hit her with an entirely different kind of life-changing knowledge: a high risk for breast cancer.
Browsing through the health and trait reports the company provides, Diamond reached the locked reports, which contain information about genetic variants that increase risk for developing breast cancer, Alzheimer’s disease or Parkinson’s. Customers have to choose to “unlock” that information since it can bring upsetting news.
Diamond considered her family history. “Because we have Alzheimer’s and Parkinson’s in my family, I said, ‘OK, I’ll think about those. But we don’t have breast cancer, so I’ll open this BRCA thing,’ ” she says, referring to the family of genes linked to breast cancer.
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To her shock, Diamond learned she has a variant in her DNA that alters one amino acid in the BRCA2 protein, putting her at high risk for the disease. “One little stupid mutation. One amino acid. And it changes your whole life.”
The next morning she called her doctor, who sent her to a genetic counselor. The counselor ordered a confirming DNA test from a lab certified to do medical diagnostic testing. Diamond also got a mammogram, an MRI, an ultrasound and blood work to screen for breast, ovarian and pancreatic cancers, because her variant boosts risk for all three. The MRI revealed a tiny spot of cancer deep in her breast, too small for the mammogram to detect. She decided to have a double mastectomy.
Genetic testing goes mainstream
This feature is part of a multipart series on consumer genetic testing. See the whole series.
Her doctors are urging her to have her ovaries and fallopian tubes removed as well, to head off ovarian cancer. “I’m not ready to do that yet,” Diamond says.
Diamond had been mostly interested in what her genes could reveal about her family history, not the health information they hold. But millions of genetic testing customers want to know their medical future. Even though most consumer genetic testing companies collect data on thousands of gene variants that may have an impact on health, companies such as 23andMe are allowed to give only limited information about genetic health risks. The companies’ reports focus mainly on ancestry or basic physical traits (SN: 5/26/18, p. 20).
So the marketplace has devised a work-around: Consumers who want to know about their risks for diabetes or several other diseases can turn to third-party services to analyze the raw DNA results generated by testing companies. New research suggests, however, that some of the answers people find through these third-party services are wrong and could prevent people from listening to their doctors or genetic counselors. That is, if the person bothers to go see one.
The market responds
Diamond got her health-related results in 2013, just before the U.S. Food and Drug Administration told 23andMe to stop giving consumers health information. The company had to demonstrate to the FDA that the information it provides is accurate and communicated in an easy-to-understand way. In 2017, 23andMe won approval to slowly add back reports for certain health conditions.
Most recently, in March, the FDA granted approval for the company to tell customers if they have one of three genetic variants in the BRCA1 and BRCA2 genes. Those three variants are responsible for about 74 percent of inherited breast cancers among people of Ashkenazi Jewish heritage. Less than 0.1 percent of people of other ethnicities carry these variants.
Offering information on only three variants, when there are thousands in the two genes that increase risk for breast and ovarian cancers — as well as melanoma, prostate and pancreatic cancers — is troublesome, say health care providers, breast cancer advocacy groups and others.
One little stupid mutation. One amino acid. And it changes your whole life.
With only a partial list of variants called out, test takers who don’t carry one of those variants may misinterpret the results, worries Lisa Schlager, vice president of community affairs and public policy for FORCE, a hereditary breast cancer information and support group.
People who don’t carry one of the variants may say, “I don’t have a genetic risk that predisposes me to cancer. I’m safe,” Schlager says. “But that is absolutely not correct you are only negative for three out of thousands of possible mutations. So our concern is that the public is not going to understand the limitations.”
Yet Schlager and others admit that allowing companies like 23andMe to provide FDA-approved information and explain the results — however incomplete — may be the lesser of two evils.
“There’s a sort of underworld that’s been going on since the FDA stopped 23andMe from interpreting these results and giving them out to people,” Schlager says. For a small fee, third-party analysis services stand eager to offer the interpretation that testing companies choose not to provide, or aren’t allowed to provide under FDA rules. These services include Promethease, an early player in the consumer raw data analysis market, along with Genetic Genie, LiveWello and many, many others.
That’s possible because customers of direct-to-consumer DNA testing services such as 23andMe, AncestryDNA and Family Tree DNA can download their raw DNA data to send to third-party analysis sites or apps. Those raw data consist of a list of spots, known as SNPs (pronounced “snips”), where customers’ DNA varies. Some third-party analysis services will also look at a wider swath of information, data on protein-coding regions, called the exome. Genos is one testing company that provides raw data on the exome.
Helix, a testing company that provides “exome plus” data, has partner apps that customers can buy to analyze limited sets of their data. (Or, for $499, you can download all of your raw data). So far, very few of the third-party analysis services are set up to process data from the entire genetic instruction book, or genome.
To write their reports, Promethease and the others find scientific studies that mention the genetic variants a customer carries and make inferences about the health risks of carrying those variants. “That has been an absolute nightmare,” Schlager says. Consumers don’t understand the information and often overreact.
Devil in the data
In Facebook groups for people with BRCA mutations, Diamond, who volunteers with FORCE, often encounters people who got a scary result from a third-party analysis site. “I have to talk a lot of people off the ledge,” she says. “They will upload their data and these services tell them, ‘You’re BRCA2 positive.’ They understandably freak out.” Many of those people would get an entirely different answer from medical diagnostic testing, she says.
Diamond makes a good point, says Stephany Tandy-Connor, a genetic counselor at Ambry Genetics in Aliso Viejo, Calif., the kind of clinical diagnostic company that doctors use for testing. She and colleagues examined test results of 49 people who received worrisome reports based on raw data generated by direct-to-consumer genetic testing companies between January 2014 and December 2016.
The people had gotten a doctor’s order to get retested by Ambry. The company did comprehensive testing of the supposedly faulty genes. More than half of the harmful variants (60 percent) flagged by consumer tests were verified by Ambry’s clinical test. The problem was, 40 percent of the harmful variants were false positives, the researchers reported March 22 in Genetics in Medicine. The results misstated that the people carried the variant when they actually didn’t.
The fault doesn’t lie with the third-party analysis service, Tandy-Connor says. Those companies simply analyze the raw data received from consumer testing companies. The errors were in the raw data. Often the testing companies are aware of the mistakes, but when they don’t use that information themselves, they don’t always bother clearing errors from the raw data, Tandy-Connor says.
Plus, the raw data don’t contain a full draft of a patient’s genome, as some consumers mistakenly think, Tandy-Connor says. Those data report only a few genetic spelling variations. Clinical testing labs, such as Ambry, use several methods to examine and reexamine disease-related genes to uncover all possible harmful variants. If each gene is a chapter in the body’s instruction manual, clinical tests read every letter in that chapter hundreds to thousands of times, Tandy-Connor says.
Clinical labs also check to see if paragraphs or even pages have been ripped out or glued into the chapter. Such missing or added information, known as structural or copy number variants, might affect more than one gene (SN: 4/25/09, p. 16).
Contrast that approach with the genotyping, or SNP testing, provided by 23andMe, AncestryDNA and many other direct-to-consumer companies. “Basically they don’t read the whole chapter,” Tandy-Connor says. “They just spot-check three or four letters and don’t even look at the rest of it.”
A clinical lab checked worrisome results that people received from consumer DNA testing companies. Of the variants flagged as harmful, 40 percent were false positives. All but one of the bad calls were in cancer risk genes: BRCA1, BRCA2, TP53, CHEK2, MLH1 and ATM.
Source: S. Tandy-Connor et al/Genetics in Medicine 2018
Filling a gap
In 2006, even before 23andMe started offering consumer DNA tests, geneticist Greg Lennon and bioinformatician Mike Cariaso wanted to learn more about their own DNA. The two compiled SNPedia, a Wiki-style database of SNPs that are linked to diseases and traits in the scientific literature. Lennon and Cariaso’s app, Promethease, uses SNPedia to compile reports about the genetic variants in a user’s raw data.
The reports consist of long lists of variants with a description of what the scientific literature says about each variant. So even though 23andMe and other companies may not be allowed to give customers that information, Promethease can. Lennon says the difference is that his service doesn’t generate any DNA data. He simply serves up scientific literature pertaining to the data.
“If the science is credible, we’ll tell you about it,” Lennon says. “We are not going to suppress information.” It’s then up to the customers, their doctors and genetic counselors to decide how to proceed. “The flip side is that it’s easy for someone to misinterpret what they see in a Promethease report and panic over it,” he admits.
Consumers shouldn’t just assume that the information contained in their raw data is correct, or that third-party services have interpreted it correctly, Tandy-Connor says. In fact, genetic testing companies say buyers should beware of using raw data as medical information.
“Uninterpreted raw genotype data, including data that are not used in 23andMe reports, has undergone a general quality review. However only a subset of markers have been individually validated for accuracy,” Dave Hinds, a statistical geneticist at 23andMe wrote on April 23 in an “Ask Me Anything” forum on the website Reddit. <
Don’t schedule any surgeries or screenings until you can talk it over with a professional.
Genetic results should be confirmed in a clinical lab, Tandy-Connor adds. And, importantly, the information needs to be evaluated in the context of a person’s overall health and family history. “Take it to your doctor. Take it to a genetic counselor or some other genetic professional,” she says. “Certainly don’t act on it. Don’t schedule any surgeries or screenings until you can talk it over with a professional.”
Lennon doesn’t quibble with that advice. “We are 100 percent in agreement that anything seen in a consumer test should be confirmed,” he says.
But the message consumers take away from the Ambry study could have the opposite effect, he says: encouraging people to ignore the results of a consumer test.
“To say there are 40 percent false positives may dissuade people — people who are really carrying mutations — from having these things clinically checked out,” Lennon says. These people might think their result is also a false positive. “That kind of blanket message is a huge disservice to people who might otherwise have actually gone in and gotten confirmatory screening.”
Tandy-Connor disagrees. “I can see the angle he’s coming from, but I don’t share the same sentiment. I’m fairly confident most people would follow up. I mean, why else are they even doing this in the first place? If you’re not going to do anything about it, what was the point? Just freak yourself out and walk away?” Not likely.
Customers of 23andMe who want to unlock information on their breast cancer risk must click through several screens of information before learning the result. This screen explains that risk goes beyond the three variants reported.
Matters in their hands
Consumers are using these third-party apps, but, according to a recent study, at least some people are taking their results to doctors and genetic counselors, says Catharine Wang, a behavioral scientist at Boston University School of Public Health. In an online survey on several social media sites, Wang and colleagues found that of 478 people who did a direct-to-consumer genetic test, 321, or more than two-thirds, used third-party analysis services to investigate ancestry or health information or both.
About 30 percent of those 321 people shared their results with a medical provider and 21 percent shared results with more than one provider, the researchers reported last year in Molecular Genetics & Genomic Medicine. Wang wasn’t surprised that not everyone brought their results to their doctors. “If you don’t find anything in your results, you’re not going to show it to your doctor,” she says. The study did not determine what percentage of people got a worrying result.
Those people who did tell their doctors about their results weren’t always happy with the responses. Doctors were dismissive, weren’t interested in the results or didn’t know what to do with them, 23 percent of respondents reported. Other times, patients had to educate their physicians about DNA testing. Some consumers went straight to genetic counselors.
used third-party analysis services in a survey of 478 individuals who took consumer genetic tests
of those 321 people shared their results with a medical provider
In a separate online survey of 85 genetic counselors, about half said that they had been contacted by people who had used a third-party interpretation service, Wang and colleagues reported January 29 in Translational Behavioral Medicine. Counselors reported that patients turned to raw data analysis for several reasons: to get answers about mysterious symptoms, out of curiosity or to find out more about their health risks, including disease risks that the patients might pass on to their children.
According to the counselors, sessions didn’t always go well. “They were encountering resistance from the patient,” Wang says, as the counselors tried to correct misconceptions. Some consumers were overconfident about their knowledge, even when they were wrong. When counselors attempted to explain how DNA testing works and that raw data may contain errors, some people didn’t want to hear it. “Consumers just don’t know these nuances,” Wang says. “Sometimes they’re just not receptive to the information.”
Some third-party interpretation services get into shady territory. LiveWello and Genetic Genie sometimes suggest clients take various vitamin supplements based on variants in certain genes. Some of the supplements are supposed to control DNA methylation, an important part of gene regulation, and reduce levels of a chemical called homocysteine in the blood. DNA methylation is a complex and delicately balanced system. Messing with it could cause problems.
Plus, methylation can’t be gauged by looking at someone’s DNA variants, says Preston Estep III, cofounder and chief scientific officer of Veritas Genetics. “SNPs cannot tell you — no amount of genetic information, actually, can tell you — what the state of your DNA methylation is,” Estep says.
To be fair, the LiveWello website says it is not giving advice and people should talk to their doctors before taking supplements. But the disclaimer is easy to overlook.
A peek into the womb
Genetic tests are a whole other ball game in the womb. They offer unprecedented detail about fetal genomes. But whole-genome tests aren’t ready for widespread use yet, doctors caution. See the companion story by Laura Sanders.
The tendency is to think that any change to DNA automatically means disease. But that’s not the case, says Gail Jarvik, a clinical medical geneticist at the University of Washington in Seattle. Some genetic diseases affect a small subset of people who carry the variants. For instance, just 24.4 percent of men and 14 percent of women who have two copies of a variant in the HFE gene will develop hemochromatosis, an organ-damaging iron buildup, Jarvik and colleagues reported in 2015.
Even for DNA changes that are strongly linked to disease, like those in the breast cancer genes, disease is not definite, Jarvik says. About 72 percent of women who carry a cancer-associated variant in the BRCA1 gene and 69 percent of women with a harmful BRCA2 variant will develop breast cancer by age 80, researchers reported last year in JAMA. “But a bunch of these women will never get breast cancer, even if they live a long life,” Jarvik says.
Because of the 23andMe test, Diamond knew her odds of getting breast cancer were high. But until her doctors found the cancer, she didn’t know if she might escape genetic fate.
“During the time between getting the 23andMe results and the cancer results I did a lot of, ‘Do I even want to know this?’ ” Diamond says. Ultimately, she is glad she knew. “They talk about early detection, but this was super early. Nothing on the mammogram. Nothing that you could feel. It’s the best-case scenario for having cancer, I guess.”
Diamond told her extended family that she carries a cancer-causing BRCA2 variant and suggested they get tested, too. Many more people in Diamond’s family turned out to carry the variant than expected for a genetic change that has a 50/50 chance of being passed on to the next generation. “We just lose the coin flip a lot,” she laments.
Diamond says she never would have known she was at risk for breast cancer if not for the consumer test. She’s now grateful she and her family have the information, but says she’s wary of getting similar information from a third party.
“There’s goodness in being able to get your raw data,” Diamond says. Uploading raw data from one ancestry site to another allows people to find more long-lost relatives. “But when you upload it to these other services to get medical information, that’s what’s more dangerous … because people may interpret it for themselves incorrectly.”
Questions or comments on this article? E-mail us at [email protected]
A version of this article appears in the June 9, 2018 issue of Science News.
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