What if you could get an idea about the genes you carry, along with predictions about what your health might be in the future — the heart attack you are at risk of suffering by age 60 or the memories you’re at greater than average risk of losing to dementia by 75 — followed by a tailored plan to help improve those odds or at least help you to prepare? That sounds like information that might be worth having, doesn’t it?
For most of us, it probably also sounds like a reality largely reserved for some time off in the future. Genetic information is getting easier to come by, but it still isn’t something everyone yet has on hand. Or is it? What if there were a simple, cheap, low-tech way to get started toward those answers today?
As it turns out, there is, and it isn’t even anything new. It’s as fundamental as answering a question you’ve probably been asked before and scrawled at least a partial response to on a piece of paper in a doctor’s waiting room somewhere: What diseases run in your family?
National Institutes of Health Director Francis Collins has referred to family history as “a window into the heritable factors that every individual has in their DNA.” Many, if not most, diseases have some genetic influence, some of them more clearly and significantly than others. Charting a family’s health history is a step toward uncovering any unusual patterns of disease that might be lurking there, whether anyone has bothered to take notice of them or not.
While clear patterns of inheritance are expected for diseases with strong genetic influences, family history can be especially telling because relatives typically share behavior patterns in addition to their DNA, and when it comes to health risks, those features can be worth noting as well. As the nonprofit health advocacy organization Genetic Alliance explains, “Family health history tells more than just what diseases run in a family. It includes information about where the family has lived and what kind of work and activities they do.”
“Family history is a major tool for gauging genetic risk of disease,” says Charis Eng, director of the Cleveland Clinic’s Genomic Medicine Institute. “It’s a wonderful, inexpensive, quick snapshot of genes and environment. Family history is the sum total of what you inherit and what you are exposed to. Once you identify someone at high risk, you can proceed to the next stage of evaluation by genetics professionals, and testing can begin if a gene is known.”
Let’s step back and recall some basic biology. For every gene, individuals inherit one copy from their mother and one from their father. Some diseases are relatively simple, meaning that they can be attributed to a single disease gene — Huntington’s disease or cystic fibrosis, for example. In the case of Huntington’s disease, it takes only one copy of the disease gene, passed down from either parent, for a person to get sick. For cystic fibrosis, it takes two.
Other common diseases, such as asthma and heart disease, are often considerably more complex. They are under the influence of many genes, working independently and together in ways that scientists are still trying hard to understand in many cases. For simple, single-gene diseases and more complex ones, too, family history can be an indispensable tool.
When it comes to those more complex and less clear-cut conditions, experts may refer to a measure known as heritability: the variation within a population that can be explained by genetics as opposed to environmental factors or random chance. At one extreme, traits such as curly hair and eye color depend almost completely on the genes an individual carries and have heritability approaching 100 percent. For a selection of common traits and conditions, the human genetics wiki SNPedia has assembled a table of heritability estimates based on some of the latest scientific evidence. Alcoholism comes in at 50 to 60 percent, Alzheimer’s disease 58 to 79 percent, anorexia 57 to 79 percent, asthma 30 percent, attention deficit disorder 70 percent, and autism 30 to 90 percent. And those are just the conditions that start with the letter A.
Sometimes genes and environmental influences can interact in surprising ways. A study of more than 1,800 pairs of twins by researchers at the University of Washington’s Medicine Sleep Center found that the heritability of body weight decreased as people slept longer. The discovery led the principal investigator to suggest that getting too little sleep somehow creates a “permissive environment” for the genes that predispose people to obesity.
In other words, context matters. Heritability is a measure of the genetic contribution of traits within a population — a particular group of people — not within any one individual. The fact that a condition often runs in families and is highly heritable doesn’t mean that it’s a done deal or that there’s nothing that can be done about it either. That’s the whole reason that collecting an accurate and complete family health history and putting it to work has the potential to be so useful.
Think of it this way: If 30 percent of the variation in blood pressure depends on genetics, then the other 70 percent depends on other factors, at least some of which might be modified through diet, exercise, and lifestyle. While healthy living is a safe bet for anyone, family history can help to uncover those people who really need to take extra precautions of one kind or another or undergo more careful monitoring.
Time to Get Personal
Collecting family history might sound simple enough, but oftentimes our knowledge of relatives and the past may be spotty or completely missing in places. You might know that someone had breast cancer, for example, but not at what age she was diagnosed, which can make a big difference, too. Even if you have a complete family health history, doctors often find it challenging in the limited time of an appointment to evaluate that history adequately. They might not have the tools to translate family history into a reliable assessment of health risks. In many cases, use of family history for keeping people well is still superficial at best.
At the Cleveland Clinic, Eng is part of a team that is trying to change that, by integrating family history into the evaluation of as many patients as possible, starting in the primary care clinics, where the focus is on prevention. To streamline the process, they’ve developed a tool called MyFamily that allows patients to enter family health history data and submit it to their doctors before they arrive at the clinic. In its beginning phase, the tool offered clinical-decision support based on that family history information for a short list of conditions, with a heavy focus on cancer: familial breast cancer, colorectal cancer, hereditary breast and ovarian cancer syndrome, abdominal aortic aneurysm, diabetes, and more.
“We are trying to focus on diseases for which there are clinical next steps to guide preventive-care planning or more treatment-based intervention,” says Megan Doerr, a genetic counselor at the Cleveland Clinic. She says that MyFamily now includes more than a dozen disease-risk algorithms and the goal is to add more each year. There are now about 60 conditions for which information about personal risk can be clinically useful.
While patient-outcomes data will take time to gather, early indications are encouraging. In a recently published report by the Cleveland Clinic team on early experiences with the tool, patients noted universally positive effects on their care, including better quality, personalization, and engagement.
“Clinicians in general have embraced the concept,” says Kathryn Teng, director of the Center for Personalized Healthcare at the Cleveland Clinic. “It has helped them do a better job of using family health history and spend time not collecting that history, but having impactful conversations [with their patients]. ‘You are at risk. Let’s talk about what we can do — diet, exercise, tests, who do you need to see — to stay healthy.’ ”
While collecting family histories doesn’t necessarily require any particularly high-tech solution, electronic tools like MyFamily and others aim to make it useful by integrating the information into electronic health records and providing physicians with feedback about how best to use it.
“Family history collection is standard of care,” says Lori Orlando, a primary care doctor at Duke University Medical Center. “Everyone knows you should do it, but that doesn’t mean they know how or what to do with the information. We hadn’t gone a step further to say, yes, electronic tools can do better.”
Orlando is part of another effort to change that by integrating electronic family histories into patient health records and clinical care using a tool called MeTree. The tool collects information on about 55 conditions, offering decision support for a few, blood clots and various cancers among them.
MeTree was put to work and evaluated first in two North Carolina primary care clinics, identifying 44 percent of patients as needing additional screening or treatment measures, including early colonoscopy, breast MRI, or genetic counseling. They are now enrolling patients at several other sites across the country.
In Orlando’s experience in her small primary care practice alone, use of family history has led on more than one occasion to the diagnosis of Lynch syndrome, a disorder characterized by increased risk of several cancers, including colon cancer. People with Lynch syndrome often undergo aggressive preventive measures, including removal of ovaries. Those Lynch syndrome diagnoses had been missed before, despite the fact that those patients had truly devastating family histories of cancer. In another instance, a strong history of breast cancer among the women in a father’s family led Orlando to recommend him for genetic counseling and testing for the BRCA genes.
“When patients get to a cancer clinic, the focus is on the cancer,” Orlando says. “They are not thinking about the bigger picture — the possibility of a syndrome and multiple cancers. Primary care doctors have so many other responsibilities, and it can be complicated. That’s why tools are nice. They offer support that’s needed, especially when doctors don’t have but seven minutes with a patient. It has definitely changed the way I practice.”
For the Cleveland Clinic’s Doerr, there is reason for considerable optimism. “There are a number of health systems really visioning the way family history can be used to judiciously apply preventive care and other types of care to patients,” she says. “It’s an exciting thing to see this all pushed on by healthcare reform and the mandate that we keep patients healthy as long as we can.”
Questions of Inheritance
Family history surely won’t become any less valuable, even as more doctors and health systems gear up to consider genomic information directly in the diagnosis and treatment of more and more patients. Julianne O’Daniel is a genetic counselor at the University of North Carolina, Chapel Hill, where she is involved in a project called NCGENES (North Carolina Clinical Genomic Evaluation by Next-Generation Exome Sequencing). NCGENES aims to use next-generation sequencing of exomes — the most studied 2 percent of the genome that consists of protein-coding genes — for the diagnosis of patients, especially those with childhood cancer, a strong family history of cancer, or developmental disorders.
The project will attempt to sort out ways to handle another category of information that genomic information unavoidably delivers: incidental findings not related to the primary condition or symptoms of concern but with the potential to be medically actionable or informative nonetheless.
One thing is for sure. When you look at something as big as the genome, you are bound to find potentially bad news that you weren’t looking for at all. Some of that information might have health implications, either now or in the future. The question is: Under what circumstances is it appropriate to turn that information over to a patient? Imagine this scenario: A patient is under evaluation based on a history of early cancer and a variant associated with a cardiac arrhythmia turns up. Is that information certain enough for a doctor to share?
A recent paper in Genetics in Medicine led by Robert Green of Brigham and Women’s Hospital and Harvard Medical School recently sought the opinions of experts on the return of selected variants in 99 common conditions. For 21 of those conditions, the clinical genetic or molecular medicine specialists agreed that the variants, if found, should be given to patients. For 64 other conditions, 80 percent of experts thought the information was sure and valuable enough to return. For the rest, feelings were much more mixed.
But, O’Daniel says, if the molecular-level findings can be put into context — with information about patient preferences, personal health history, and family history — suddenly those decisions can become much more clear. Before raising any alarm bells for a patient, family history, together with other information, can help doctors and genetic specialists answer the question: Is this variant likely to cause a health problem?
“Family history could potentially impact whether we think something is ‘real’ or not,” O’Daniel explains. “Depending on the evidence we have about a variant, that’s how we might determine what to return or not. If it’s an incidental finding, in our mind, we need to be pretty sure that it’s pathogenic.
“The difficulty is no one may have ever asked the question,” she says. In the example of a cardiac arrhythmia variant, “the history may be there — a sudden death or SIDS death perhaps. The person sitting in front of you with a neuromuscular disorder may not think to disclose that information because it seems unrelated.”
Back to Our Roots
The excitement about what might happen when family history and genomics meet in a clinical setting explains the big interest in a tiny series of islands halfway between Iceland and Norway. With a population of 50,000 and a long and isolated history, the Faroe Islands is on track to become the first nation to offer genome sequencing to all of its citizens. The health records in the Faroes have been completely digitized, along with detailed pedigrees of family relationships. The project, known as FarGen, is now in the pilot phase of adding genomic information into that mix.
Bogi Eliasen, FarGen’s program director, says the Faroes are a rather unusual place, in that those who choose to remain there keep close ties to family in a way many in more urban environments don’t anymore. A political scientist by training (not a biologist or clinician), Eliasen has a grand vision for what this kind of comprehensive and proactive information about health risks could mean for society.
“The beauty of genomics is not to make everybody the same,” Eliasen says. “I think that family history is a good reminder that we are different — not just on genetic letters, but we can actually see the difference. … What we used to do is treat different people the same. What we can begin to do is set individuals free to be whatever they are.”
History for the Future
The Faroes have other simplifying features beyond the small size of their population and record-intensive health system. It is a very equitable society by any measure. For all practical purposes, the people living there are not divided into haves and have-nots, and they generally remain in close contact with their immediate and extended families.
In the United States, by comparison, people often don’t know a whole section of their family history, O’Daniel says, perhaps because of adoption, a relationship that ended, or other circumstances. “It’s not unusual that people might have no information about one side of the family. From a genetic standpoint, that can be very limiting. It might change our diagnostic testing approach. We might want to cast a wider net because of lack of knowledge or make it more targeted for the same reason.”
Even without complications in the immediate family, information often grows poor when it comes to grandparents. As people and clinics begin to adopt the newly available tools, there’s considerable hope for improvement.
“There has been so little information [about family history]. If we start collecting it and passing it down, it will be there for future generations,” Duke’s Orlando says. It’s worth doing even for those who don’t have a particular history of illness. “If something changes, we can pinpoint where the problem is; it’s still important for sharing.”
Orlando urges individuals to find out the age of relatives at the time a disease was first diagnosed. Those details can often be fuzzy, and sometimes age cutoffs really matter. In the case of cancer, it’s important to differentiate between where a cancer started and where it spreads, too.
Generally speaking, there might be cause for concern if more than three relatives on one side of the family had cancer or another condition or if the disease was diagnosed relatively early. Other qualitative details can be important to note, too. In the case of melanoma, for example, one first-degree relative with the disease increases your risk by a factor of two to three. If there are multiple affected relatives and a history of pancreatic cancer, too, or a family member has more than one skin cancer lesion, the risk can be much more significant. In general, any three individuals with the same condition can suggest a pattern worth talking to your doctor or a genetic counselor about.
If you don’t have the opportunity this summer, make a plan to recognize Family History Day at Thanksgiving this year. “I always chuckle,” O’Daniel says. “You get around the table and all talk about your illnesses anyway. It’s a good time for someone to start writing it down.” The details can later be entered into the surgeon general’s My Family Health Portrait online, which can be shared and accessed by multiple family members and your doctor.
Whatever the starting point, don’t be afraid to ask questions. “I thought I knew my family history fairly well, but I had to ask my mom a couple of questions to verify things,” Orlando says. “And I should know; I’m a doctor.”