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Personalized Genomics: A Very Personal Post

Both 23andMe and deCODEme (using my 23andMe data) have interpreted my SNP results to indicate that I have a greatly increased genetic risk for Type 2 Diabetes.  This post interprets the information from both companies and applies some of the primary research that the companies relied upon to predict my risk.  Hopefully, this information will be useful to me as I strive to more completely understand my own risk factors, and will be useful to others as an example of using SNP data to potentially understand more about your health.

I. The Genetics

My 23andMe analysis makes it clear that I have an elevated risk for type 2 diabetes:

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And, upon clicking upon the link, I receive the following additional information:

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deCODEme, which used my 23andMe data, provides a similar interpretation:

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Three of the major risk alleles analyzed by both 23andMe and deCODEme are the following (with my genotype for each allele).  There are others, but interestingly these three have been examined together in several studies.

Gene

SNP

My Genotype

Relative Risk

(23andMe/deCODEme)

Genotype

Frequency

KCNJ11

rs5219

TT (aka E23K)

1.17/1.19

12.2%

PPARG

rs1801282

CC (aka Pro12)

1.02/1.03

81.0%

TCF7L2

rs7903146

TT

1.59/1.54

7.8%

(note that the rs5219 SNP – which is the risk allele from numerous research studies -  is 90% correlated with rs5215, which is the SNP tested by deCODEme, so keep this in mind if you tested with that company).  You can learn more about the other two SNPs at SNPedia (rs7903146 and rs1801282).  EDIT - a previous version stated that 23andMe tested the correlated rs5215 SNP; that was incorrect.  23andMe does test the rs5219 SNP.

As you can see, from the six possible risk alleles for the above three SNPs, I happen to have all six!

Apparently this is very rare, as is shown in this Figure 2 from an October 2006 article in PLoS Medicine (Weedon et al. (2006) Combining Information From Common Type 2 Diabetes Risk Polymorphisms Improves Disease Prediction. PLoS Med 3(10): e374. DOI: 10.1371/journal.pmed.0030374):

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Only about 1-2% of the >6,000 people in that study had all six risk alleles. The researchers found that each additional risk allele increased the odds of type 2 diabetes by 1.28 times, and participants with all six risk alleles had an odds ratio of 5.71 compared to those with no risk alleles.  From the paper:

“An alternative way to assess the impact of susceptibility alleles on disease risk is to use positive predictive values. Assuming a background risk of 5% in the general population, the probability of people with zero risk alleles developing type 2 diabetes is 2% compared to 10% for people with all six risk alleles.”

The presence of all six alleles, therefore, doubles the risk of developing type 2 diabetes. Indeed, both companies interpreted my genotype to suggest a vastly increased lifetime risk for diabetes. 23andMe showed a 35.9% lifetime risk compared to 23.7% for the general public (an increase of 51%), while deCODEme showed a 40.2% lifetime risk compared to 25% for the general public (an increase of 61%).

II. The Family History

Not surprisingly, I have a strong family history of type 2 diabetes. I won’t give any further specifics to preserve anonymity (as much as this has already revealed half the genotype of each of my parents), but I can say that type 2 diabetes has had – and continues to have – an impact on close relatives.

III. Conclusions

So what does this all mean? And why post about such a personal issue?

In some ways this post is to further prove the point that I, personally, am not afraid of my genetic information. I’m not afraid of any potential psychological effects it might have, nor am I afraid of any repercussions of sharing my genetic information with others. It is certainly clear that I lost the genetic lottery when it comes to diabetes risk, but there is no genome so perfect that it lacks at least one serious risk. Accordingly, when discriminating against others based on their genetic information, we are discriminating against our own imperfect genome.  By discovering or sharing our genetic information we not only learn about ourselves as a singular person, but we learn about the larger ‘ourselves’ as a species.

Further, this post is my attempt to rebut the notion of genetic exceptionalism, the idea that genetic information is somehow different from other types of personal information and thus requires an increased level of scrutiny and/or protection. For me personally, interpreting my genotype is no more dangerous than the receiving the results of a home glucose test. Indeed, the results of the glucose test represent a current reality while the genotype merely suggests a future possibility.

Although I won’t go so far as to say that there is never any danger to anyone upon receiving genetic information, I will go so far as to say that it should be the individual, not the government, that decides whether the danger exists.

IV. The Future

The fact that I’m not afraid of my genetic information, or that I don’t believe in genetic exceptionalism, doesn’t mean, however, that I should ignore my genotype.  In my case, my genotype has reinforced and added to my understanding of my diabetes risk, and it would be foolish to waste this opportunity to shape my future.

Time to hit the gym.

Blaine Bettinger

Intellectual property attorney, genealogist, and author of The Genetic Genealogist since 2007

27 Comments

  1. I applaud your decision to share this information, Dr. DNA. It has certainly reinforced my decision to have mine done as soon as possible.

  2. I know someone who tested through 23andMe and has a diabetes result very close to yours. He told me that diabetes runs on his father’s side of the family so the result didn’t surprise him any. He’ll be 90 this year and has never developed diabetes. But then again, he’s never been one to woof down a plate of sugar cookies either.

    Its like receiving knowledge that there may be a “tipping point” within you. Whether its avoiding sweets or going to the gym, the knowledge of your genome can keep good health tipped in your favor. I wouldn’t be surprised at all if you also made it to 90 with no diabetes!

    Thanks for sharing, Blaine!

  3. Thank you all for the kind words! Digging into and writing about my genetic information for this post was both interesting and rewarding. I feel very lucky to live in an era in which I can peer into my genome and find this type of useful information.

  4. See http://varigenome.blogspot.com/. My colleagues have reported that the same TCF7L2 variant associates with postprandial lipemia (after-meal levels of blood lipids) but that relationship is modulated by PUFA (polyunsaturated fatty acid) intake. See http://www.ncbi.nlm.nih.gov/pubmed/19141698, where “high (n-6) PUFA intakes (> or = 6.62% of energy intake) were associated with atherogenic dyslipidemia in carriers of the minor T allele at the TCF7L2 rs7903146 SNP and may predispose them to MetS, diabetes, and cardiovascular disease.” Links between dyslipidemia and T2DM are well established.

    In other words, the interplay between environment and genome is an important consideration that is often overlooked.

  5. Thanks for posting this. I was impressed by the efforts used by these companies to convey risk – particularly in showing that a small increase in risk for a common disease is probably more important to you than a big increase in risk for a rare disease.

    For more on risk portrayal, there are some nice animations at:

    http://understandinguncertainty.org/

  6. Blaine,

    Like you I have a family history of type II and my father died of complications from it. It has been known from way before genetic testing became available, that first degree relatives of type II patients have an enhanced risk. For over 35 years I have done the exercise and diet stuff…I love exercise and my diet restrictions are not intense nor onerous so it has been no real sacrifice. Even though I am a geneticist, I have never felt that being tested for a genetic predisposition for type II was a priority although of course I have an interest in my genotype. My life style would not change regardless of the outcome of the test. If it revealed that I was not at an increased risk I wouldn’t believe it knowing that these tests are of limited accuracy. There are surely more variants that affect susceptibility that have yet to be discovered.

    Nonetheless I enjoyed your posting and learned something.

  7. Very interesting post on many levels. No, not everyone should be “afraid” of their genetic information, but each person of course has the right to make his/her decision. If you have a family history of Huntington’s disease, it would be a very difficult decision to be tested or not to determine which genetic lottery ticket you have drawn. And there are good reasons for not revealing your genetic information in regards to employment, insurance coverage, etc. (refer to GINA legislation). It’s not always simple, but it is always personal.

  8. I don’t think anyone should be scared of their genetic information – we may not like it but at least if we aware of any genetic issues we can try to modify our lifestyles accordingly and try to minimize any risks.

  9. “By discovering or sharing our genetic information we not only learn about ourselves as a singular person, but we learn about the larger ‘ourselves’ as a species.”

    I totally agree. In addition, I would like to wish you a fruitful tenure as the new editor of the Journal of Genetic Genealogy.

  10. I have tested with 23andMe, and posted my raw dna data over to deCODEme. I have a similar deCODEme risk for Diabetes type 2 as you. Not sure about 23andMe’s except it is higher than the average risk. Unlike you, I have no family members with diabetes and my doctor recently sent me for a 2 hour glucose stress test the result of which was in the normal range. Doctor’s seem more proactive in picking up disorders before they cause serious effects than they used to be in the past. That goes for hypertension, prostate problems and the possibility of cancers in men and women.

    I for one don’t see anything particularly personal about my genetic data. Just variations on a theme all humans have. I would post my results, particularly from the Promethease Report but don’t think it would particularly interest anyone.

  11. Wow that was unusual. I just wrote aan really long comment but after I clicked submit my comment didn’t appear.
    Grrrr… well I’m not writing all that oer again. Anyway,
    just wanted to say superb blog!

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