Should you do a home DNA test for Alzheimer's?

Alzheimer's is a complicated disease.

There are early-onset forms and late-onset forms that have different genes involved. The risk to develop Alzheimer's as a result of genetic predisposition varies from person to person and family to family, depending on which form is going on and which gene or genes are involved.

We don't know and understand all the factors that cause Alzheimer's yet, so while genetic testing can be helpful, it oftentimes won't be able to tell the whole story. 

If you have raw genomic data you've downloaded from a consumer DNA test (like Ancestry, Family Tree DNA, MyHeritage, or 23andMe), I want you to know some of the limitations that have come to our attention. 

There are known miscalls (testing errors) happening for some of the Alzheimer's-associated DNA markers. Ancestry's chip (v2) is miscalling the APOE e4 variant as normal in those who actually are positive, for example. 23andMe (v5) seems to be having the opposite issue with falsely miscalling a SNP as positive in one of the early-onset genes.

Also, the markers included on testing at consumer companies change over time, so if you try to run an analysis on your raw data (by using Promethease, as an example), your report can change from one file to the next and vary over time. You might see things pop on one report that don't appear on another, depending on the testing company or the version of testing that was used.

My advice when people ask about results on Alzheimer's genes and the results they get back from testing at home is this: talk with a genetic counselor (like myself or someone else you find in your area) to make sure you are understanding the results, and always follow up a home-based test with a clinical test before believing them as "real".

Interested in reading more? Here are two other posts you can read about Alzheimer's and whether to find out if you might have a genetic risk:

https://www.watersheddna.com/blog-and-news/alzheimers-disease-key-points-to-know-in-light-of-the-new-23andme-reports

https://www.watersheddna.com/blog-and-news/need-help-fighting-the-urge-to-open-your-alzheimers-disease-risk-report

This is VUS

Adoption affects access to information about a person's history, most significantly for the person who was adopted. As this post reveals, it can also affect the parents who have adopted a child with complex medical needs and no clear underlying cause. This guest post is written by Michelle Seitzer, a mother whose daughter was adopted from Bulgaria at age 2. Michelle shares of the journey her family has taken to discover the reasons behind their daughter's medical issues and the search for care and treatments. The journey has been long and has included genetic testing that resulted in more questions than answers.

Michelle writes about the dreaded "VUS" (also called VOUS or a variant of uncertain significance) and her resolve to keep searching for answers to help her daughter.

Because the medical genetics community is still trying to understand how individual genetic variations affect health, the more we test the more uncertainty that often arises. Not every difference in DNA is harmful. With more than 7 billion humans alive today -- and each of them with a unique sequence of 3 billion letters of DNA -- the capacity for variation from one person to the next is nearly limitless.

Over time, variants that are at first uncertain can be "reclassified" into the category of clearly disease-causing or clearly harmless.

In the meantime, families like the Seitzers wait while the medical genetics world tries to sort them all out.   

- Brianne


seitzerpic2.png

"This is VUS" by Michelle Seitzer

When we started the international adoption process in 2011, questions became our new normal. Nearly five years later, we still have many unanswered questions—maybe more.

We recently did two rounds of genetic testing on our daughter, who is 7. When we first met her, she was 2. When she joined our family, she was a few months shy of 3. We knew she had some special needs, the main ones being mild cerebral palsy (CP) and extreme prematurity (which can cause a number of delays and deficits). We anticipated developmental delays as a result of her time in the medical-social care home as well.

The medical report we received from our adoption agency was quite extensive, and after meeting and speaking with several medical staff members in her care home, the report seemed fairly reputable and accurate (this is not always the case with international adoptions). In fact, one of the most accurate lines in her medical record—even after being translated from Bulgarian—still holds true today (though it could apply to most children at any point in time): “Reacts to prohibition with displeasure.”

We quickly learned what’s on two-dimensional paper in black and white and what happens when that multidimensional child and all her history—knowns and unknowns—collides with a completely different culture and environment. When that child becomes part of a family. When that child is given opportunities to grow and thrive in ways her care home, as competent and compassionate as its staff seemed to be, could not offer.

Over the past five years, we’ve probably seen 20-30 different doctors, specialists, therapists, and more. Some have been expected. We had been advised by the medical director of her care home to follow up with a neurologist and an orthopedic specialist for her CP, and we’ve seen several orthopedists—including a surgeon who performed double hip surgery on her in 2016—and do yearly or as-needed visits with a neurologist. But some have been unexpected. When she was four, we were referred to a sports medicine doctor for a knee condition which showed up on an MRI.

Also since her arrival to the US in 2013, she’s had three sets of ear tubes surgically placed. These are quick and easy surgeries, but her consistently poor results on audiological tests even after having new, clear tubes led our ENT (ear, nose, and throat specialist) to refer us to the genetics department at Children’s Hospital of Philadelphia (CHOP). His hope was that we’d find an underlying cause or condition responsible for her hearing loss, and to determine if that condition is progressive (because she had a comprehensive brain MRI, we were able to look at those images and rule out any nerve damage or other physical “misconnections” responsible). Knowing her complex needs, he also hoped we might find a genetic “diagnosis” that would tie together all her many loose ends. I was hopeful for the same, but if I’ve learned anything as a special needs parent, it’s that things are rarely easily explained, able to be neatly packaged, or simple. There are acronyms for just about everything, and I’m now well-versed in the alphabet soup of the special needs & adoptive parenting parenting world.

When you’re dealing with the mysteries of adoption, in our family’s opinion, some information is better than none at all.

 

We did the first round of genetic testing, a wide genome array, and were then encouraged to take the next step, whole exome sequencing (WES). It involved a blood test, exam, and a consult. Since we don’t have any family medical history or access to it, we believed whatever results were returned, the testing might at least provide some information about her current and future health needs. When you’re dealing with the mysteries of adoption, in our family’s opinion, some information is better than none at all.

We waited eagerly for the results, which came about three months later.

But true to her form of always keeping us and her doctors and therapists guessing, the WES results showed 5 genetic variations, all of which fell under the category of VOUS—variants of unknown significance. In the genetics world, "VOUS" basically means the variant could lead to nothing—it's essentially benign—or it could develop into something pathologic. Good or bad. Something or nothing. At this point, there’s not enough information to know for sure.

In the genetics world, “VOUS” basically means the variant could lead to nothing—it’s essentially benign—or it could develop into something pathologic.

 

The test we hoped might bring one “easy” answer brought us more questions. We’re sort of getting used to that. But we press on. Is it because we want a diagnosis that could mean an even more difficult future for her than the one we already might imagine? Or something that would change the tremendously positive and even independent future we also imagine? No. We don’t want a diagnosis if there’s not one to have, but when you have a child with many unexplained health issues and challenges, you do long for a simple explanation—especially because it might lead to a simpler solution than all the therapies, treatments, and interventions we have and continue to try.

The test we hoped might bring one “easy” answer brought us more questions.

You long for some glimpse of the future: will she be able to have her own children, and if so, would they have similar health issues and challenges? Will any of her current “conditions” get worse? On the flip side, as genetic research improves and advances at light speed, could we also learn of a cure? A treatment that would help her and other kids like her?

Besides learning to “speak” alphabet soup, adoption and special needs parenting has certainly taught us to expect the unexpected. To live in the pain but also the joys of uncertainties. To know her story, and ours, and the stories of all the children and adults who have undergone or will undergo extensive genetic testing, is still unfolding.

If we can get a little more clarity on what we can and can’t change, great. If by doing so we can help others in similar situations, even better. If we don’t learn anything new at all, that’s fine too. We’re grateful for the opportunity to try, grateful for every moment with our daughter, and grateful for the people who have helped us try to understand her better so we can give her the best possible quality of life. And in the end, that’s the most significant and concrete finding of all: I can live with the unanswered questions so long as we’ve done our best to answer the important ones.


SeitzerHeadshot.png

Michelle Seitzer has been writing since she was old enough to hold a pencil, but she’s been a freelance writer since 2008. Before her daughter joined their family, she spent more than a decade volunteering and working in senior living communities, and advocacy for elders continues to be one of her greatest passions. She currently lives with her family in an old stone farmhouse north of Philadelphia and loves traveling, the arts, and following interior design blogs on Instagram. Follow her on Twitter @MichelleSeitzer.

Why do adoptees want DNA testing?

Anna Childers is a genetic counselor at Vanderbilt University in Nashville, Tennessee. Last year, she interviewed adult adoptees on their perspectives on DNA testing as part of her graduate degree from the University of South Carolina. Her study queried adults who had been adopted as children about the importance of DNA testing and their motivations for pursuing DNA testing in the at-home setting.

Anna presented her results at the 2017 National Society of Genetic Counselors annual conference, and the findings were consistent with other past reports of the use and motivations of DNA testing by adoptees.

As an active participant in the world of genetic genealogy and someone who has interacted with adoptees and adoptive parents through my professional work and personal life, this topic holds special importance to me (and many others!).

In this post, Anna shares a summary of her project's outcomes with readers. If you would like more details about the project or to be kept abreast of any updates related to the work Anna has done (when full results are published publicly, for example), you can check back here on my blog over time, or reach out to Anna yourself (anna.k.childers@vanderbilt.edu).   

Great work, Anna! These results are an important contribution to the body of knowledge that will help those affected by adoption gain better access to information that may impact their health, their families, and their rights. 

- Brianne

P.S. Readers, interested in this topic? I have additional links related to adoption and DNA listed in my newly-updated resources section and also provide private consultations about various DNA topics (including health/medical) for all those affected by adoption as well as their family members.


Anna Childers writes:

The public’s knowledge about the role of genetics in disease is constantly growing. At the same time, the market for direct-to-consumer genetic testing (at-home genetic testing) continues to expand. Companies such as 23andMe and AncestryDNA allow you to order a genetic test without speaking to a healthcare provider. These test results can - depending on the company - offer information on disease susceptibility, carrier status, ancestry, and many other areas of interest.

One group of customers taking advantage of the ever-growing at-home genetic testing market is adoptees. Previous research has shown that adoptees appear to be more motivated than non-adoptees to learn about their genetic disease risk but have similar responses to health-related information. In our study, we interviewed 14 adoptees that received some sort of health information as a result of their journey with at-home testing.  We asked these adoptees about their motivations for pursuing testing, their satisfaction with their results, their emotions throughout the process, and their interest in meeting with a genetic counselor.

Adoptees described three main motivations for pursuing at-home genetic testing:

1) identity-seeking

2) a desire for health information

3) general curiosity

This idea of seeking some form of an identity, for some adoptees, corresponded with the search for biological family. For others, it meant learning more about their ethnicity. Both provided adoptees with the opportunity to connect with something bigger than themselves. One adoptee described this search, saying “people are proud of their heritage, and all your whole life, you don’t have one…a nice diverse [ancestry] to me was being able to go ‘oh gee I can associate with that, associate with that, find out about all those different cultures.’”

 Adoptees also shared a variety of emotional reactions to the newfound information, but the strongest emotional responses were reported in reaction to ancestral information, or information regarding both ethnicity and biological family. For example, silence from one adoptee’s biological family led to the feeling of being a “dirty little secret.” Another, after learning that her heritage was different than what she had been told her entire life, described the time spent looking for her biological family as “30 years of absolutely wasted time.”

Since health-related genetic testing was a theme of the study, familiarity of the concept of genetic counseling was assessed. When we asked adoptees about their interest in speaking with a genetic counselor, the majority of the adoptees found some sort of value in talking to a genetic counselor. The adoptees said that this kind of information would be useful if they were found to carry certain genetic traits, if a new health concern arose, or would be beneficial for their family members.

Genetic counselors are professionals trained in dealing with both the emotional responses and the educational questions that come along with genetic testing. The insights from this study were shared with genetic counselors during the 2017 conference of the National Society of Genetic Counselors in Columbus, Ohio. The research is also being prepared for publication and upon publication, full study results will be available for a larger audience to read and to learn.

In the words of one of the adoptees interviewed, “[adoption] affects all the generations going forward because [adoptees] missed out on that giant piece [of information].” It is up to genetic counselors to help adoptees sort through what these results might mean for them, both in the emotional and informational sense.


AnnaChildersHeadshot.jpg

Bio: Anna Childers is a pediatric genetic counselor at the Monroe Carell, Jr. Children’s Hospital at Vanderbilt University in Nashville, Tennessee. The work summarized in this blog post was completed in 2017 as a part of her graduate work while a student of the University of South Carolina’s genetic counseling program.

 

A new year, a new resources section on WatershedDNA.com!

It's a new year, and it's a new resources section for the Watershed DNA website!

Here's what part of the new section looks like.

Here's what part of the new section looks like.

I've refreshed my resources list, fixed links, added a search box, and reorganized my list of free resources to help you find your way to more information on the DNA topics of interest to you.

Sections at this time include general, ancestry, health, adoption, and donor conception. 

Check back again in the future, as I'll be updating sections and resources over time.

Also feel free to send suggestions my way if you've found a particularly helpful online resource that you think more people should know about. 

Link to the Resources section here!

- Brianne

From mentor/mentee to business co-founders: Ellen and Danielle share their story of connection in my next Base Pairs post

In the world of DNA, a base pair is a set of genetic letters that join together from opposing strands of the double helix. The two letters go together like peas and carrots. T matches up with A, and G matches up with C, composing a rung of the DNA ladder. Without base pairs, we'd have no double helix and we'd have no DNA molecule.

In the world of people, it's much the same. We rely on strong and lasting relationships to weather the storms and appreciate the calm moments of life. People find a fit and link themselves together, whether it's because they are family, they've forged an intentional friendship, or they share a common experience that bonds them for life. 

My next Base Pair is a set of genetic counselors whose relationship started unsuspectingly...just one curious student shadowing a professional working in her area of academic interest. Over time, the relationship evolved into one of mentor/mentee, then to that of co-workers, and eventually, business co-founders.

One of the takeaways from the responses I received from Ellen Matloff and Danielle Bonadies is the message of the value of creating opportunities for other people, and of fostering and encouraging their innate abilities.

Some of the best gifts we can give another person with dreams and goals are opportunities and our belief in their potential. 

I am happy to share the story of Ellen and Danielle as the next post in my Base Pair series.    

-Brianne


HOW DID YOU GET INTERESTED IN GENETIC COUNSELING?

Ellen: I took a Genetics course as a sophomore in college and a genetic counselor came in to speak to the class.  That led me to observe with a few genetic counselors, and then to do a formal internship.  Sold!

Danielle: I first got interested in genetics after my high school biology teacher showed us a video about gene therapy for cystic fibrosis.  It was the first time that learning became exciting for me.  A spark was lit and I knew that I’d follow a path in the sciences.  

DID YOU LEARN ABOUT GENETIC COUNSELING FROM SOMEONE YOU KNEW? DID YOU INFLUENCE SOMEONE ELSE TO ATTEND SCHOOL FOR GENETIC COUNSELING?

Ellen: I did not learn about the field from someone I knew, but I have been told that I’ve influenced several students who, like me, were looking for a career path and heard me lecture to their classes about genetic counseling.

Danielle: During college, I worked in a lab studying cystic fibrosis where another member of the lab was a genetic counselor.  She spent some of her time in the lab and some of her time meeting with patients.  I shadowed her and found that working with patients was a critical missing link.  

WHAT IS YOUR SPECIAL CONNECTION TO YOUR BASE PAIR BUDDY? HOW DID YOU MEET?

Ellen: I first met Danielle when she contacted me to learn more about the field of genetic counseling!  (There is a theme building here …)  She spent a day with me at my job at Yale, and then came back as our Fellowship student while she was a graduate student at Sarah Lawrence.  We then hired her as a genetic counselor as soon as she graduated!

Danielle: As I started exploring the field of genetic counseling further I reached out to several genetic counselors to shadow them. Ellen got back to me right away and I spent a few days over my winter break shadowing her. I never would have guessed that a few days of shadowing would turn into my first job, years of mentorship and multiple joint career paths.   

WHAT’S THE UNIQUE ASPECT TO YOUR RELATIONSHIP BEYOND BEING COWORKERS?

Ellen: I’ve now known Danielle for more than a decade, across different jobs, and across many different transitions in our own personal and professional lives.  We’ve climbed many mountains together, and I’m always grateful to have her on my team — never more so than when she helped me form My Gene Counsel. She is one of mGC’s greatest assets. 

Danielle: Ellen began as role model when I entered the genetic counseling field and has added such incredible depth to my career.  She’s been my boss, a colleague, a co-author, a friend and now the CEO of My Gene Counsel.  She has always been my biggest advocate and my career path has blossomed because of it. Her unrelenting support and has made all the difference in my life, both professionally and personally.  


Danielle Bonadies is the Director of the Cancer Genetics Division of My Gene Counsel, a digital health company that links current, updating, evidence-based information to genetic test results.  Danielle was previously the Assistant Director of the Cancer Genetic Counseling Program at Yale where she designed and ran several interactive, on-line patient education and communication sites, and is a well-known speaker in Genetics.  Danielle has co-authored multiple book chapters and articles in genetic counseling and testing and was involved in the publication of several key articles about the high rate of result misinterpretation amongst clinicians ordering genetic testing.

          Danielle Bonadies

          Danielle Bonadies

Ellen Matloff is President and CEO of My Gene Counsel, LLC, a digital health company offering accurate, dynamic solutions digital genetic counseling solutions to consumers and clinicians. Ellen is a certified genetic counselor who has served in a number of leadership positions in the profession, including being Founder and Director of the Cancer Genetic Counseling program at Yale Cancer Center.

                Ellen Matloff

                Ellen Matloff

How do you check out an online DNA test for its reliability?

How do you know if a DNA company you found online is reputable? And whether its results are reliable? These are common questions. And they are difficult to answer.

If you're asking about tests that will give you ancestry or genealogy information, the International Society of Genetic Genealogy is a great place to turn. Their beginner's guide section has a list of articles to get you headed down the right track. I've also written about choosing between the options in this area of DTC testing before and linked to other articles with advice in this blog post.

Companies have a lot of freedom in marketing DNA tests online and through commercials and social media posts. But not all DNA tests that claim to give you information about how your body works or what health risks you carry are the same. 

To be a savvy consumer, a website review is a great place to start. Investigating details on a company website can tell you a lot about them and how reliable their testing might be.

Here’s a checklist to help you begin your detective work. The ideal DTC genetic testing company's website should have: 

  • A description of what their DNA test(s) tells you and the technology they use to do it
  • CLIA and CAP numbers clearly listed on the home page
    • This is proof they use a lab with qualified staff and lab techniques and are abiding by at least baseline standards and that their approval is up-to-date.
    • Note that CLIA and CAP alone aren't sufficient evidence of a company's legitimacy. Even some questionable companies claim CLIA certification and CAP accreditation (review Soccer Genomics's site as an example). 
  • A toll-free contact phone number
  • An online "chat box" or email address to send questions to
    • You should get a response back within 24-48 hours, especially if the company promises a customer service team.
  • A section listing the names and credentials of their employees
    • There should be a team of scientists and on that team should be ones with advanced degrees in genetics. Their science team members should be listed by name
    • If the marketing team is a lot larger than the science team, stop and think what that might mean about the company's motivations and goals.
    • Review the "We're hiring!" section of the site, if there is one -- this can give you an idea of the company's priorities and where they are investing their resources. 
    • A company that includes certified genetic counselors on their team gets automatic bonus points! Genetic counselors tend to be pretty tough on DTC companies and expect rigorous science and high-quality testing and reporting. We see people make life-changing decisions after DNA testing, and because of that, won't settle for low-quality tests.
  • A reference section citing the medical studies that support their testing
    • Studies should be recent -- roughly within the past three to five years.
    • If an article they list is behind a paywall, you should contact the company and request to read it. They should send a copy to you. Having your emails ignored is a big red flag!
    • Studies cited should have been published in reputable* medical/science journals (*This can be hard to determine unless you are an expert in the given field of the journal; everyone should be aware there are predatory science journals that will publish anything if someone pays for it, whether or not the science is solid.)
  • Information on the site that allows you to gauge how long the company has been in business
    • Links to news articles and press releases about them, written by others
  • Sample reports you can see before deciding whether to order their test or not
    • Reports showing what both "positive" and "negative" results look like should be available, whether or not you've put a DNA test in the online shopping cart. 
  • A “Terms of Service” document and privacy policy
    • Like sample reports, you should be able to review these before you get to the online shopping cart section. 
    • Read them carefully. They should explain what happens to your biological sample of DNA (does it get stored?), who will get your genetic data after testing's complete (will it be sold to pharma?), and whether you have choices about what is done with your data. 

Beware of companies whose websites are simplistic or do not state where they are based. Some DNA companies you'll run across online are based out of countries without oversight of business practices.

There are a number of online genomics companies using shaky science to back up big claims. Don't fall for one of these! If a claim sounds too good to be true, there is a chance it is. Make sure to do your due diligence before you place that test into your online checkout cart.

A special side note: Companies that talk about testing your telomeres or mitochondrial DNA for health, medical, or longevity purposes are ones of which to be especially wary. The analysis and medical interpretation of testing on these two things are much more difficult to decipher than standard DNA testing, and bold claims about at-home tests that analyze the telomeres or mitochondrial DNA are to be approached with caution, and suspicion.

Have you already picked out a test you want but are having some reservations about ordering it or sending back your sample? Reach out for a one-time session, and I'll be happy to go through the company and its sample reports with you before you decide.