The Genetic Genealogist

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:

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

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

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.

(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):

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.

Just took the @23andMe Longevity Survey – http://bit.ly/8DYAKC about 14 hours ago  

@tgoetz: http://bit.ly/4rkgsW – looking forward to get a fitbit; finally a scientific way to tell whether it really was a bad night’s sleep about 14 hours ago  

I would have guessed more – “Americans Consume 34GB of Content a Day” at Lifehacker – http://tinyurl.com/yl8y6hc 1:47 PM Dec 9th  

I guess I should drive safer – RT @ABAJournal: Lawyers Second Most Likely Professional to Be in a Car Crash http://bit.ly/4pzRlZ 11:54 AM Dec 9th  

I use @HootSuite to filter: #mhco @Rex7 – you must filter the firehose of social media. 11:29 AM Dec 9th  

Listening to Martindale Connected social media webinar for lawyers – @nikiblack speaking re: social media stats http://bit.ly/7Jyyxq #mhco 11:18 AM Dec 9th  

RT @genomicslawyer: Genes vs. environment and the role of genomic “dark matter” http://bit.ly/5TcsTl (HT @drjonboyg) 7:55 AM Dec 9th  

(*consultant) RT @genomicslawyer: Kevin Davies of @bioitworld has a nice review of the @PathwayGenomics DTC offering http://bit.ly/83J1vD 3:33 PM Dec 8th  

Thank you very much for the Genea-Speak Award @megansmolenyak! Your award was well-deserved! http://post.ly/EPBZ 8:47 AM Dec 8th  

RT @genomicslawyer: George Church shares his thoughts “In Support of Open Access for Genomic Research” http://bit.ly/7KDkuY 8:42 AM Dec 8th  

Posted via web from Blaine Bettinger’s Lifestream

I’ve been playing with 23andMe’s Relative Finder this week, since it’s now in open beta.  It’s been interesting hearing from 6th to 10th cousins from around the world, and we’re working to find ancestors in common.  I’m looking forward to identifying – for the first time – a piece of autosomal DNA that came from a specific ancestor.

While in the beta period, the number of relatives is limited to 1000 (I currently have 173 with only 5 in the 3rd to 7th cousin range), and you can only contact other people who have opted in for the beta test. So if you have a 23andMe account, please opt in to the beta test via the following instructions (kind provided by Ann Turner):

1. Open the page https://www.23andme.com/user/profile/  and check the checkbox near “Name:” and click on the blue “Save Changes” button.

2. Open the page https://www.23andme.com/user/edit/privacy/  and UNcheck the checkbox near “I do not want to receive sharing invitations from anyone.”

3. Open the page https://www.23andme.com/you/relfinder/  and check the checkbox near “Highlight my profile in Relative Finder to show that I’m interested in making connections with potential relatives.”

Extended Profiles

Ann also wisely suggested expanding your profile to include information that will help other users find a genealogical connection.  Since the profiles are searchable by keyword, and she recommends including any special interests (regional/ethnic/etc) in the profile.  Like Ann, I included information about my genealogy back to 6 generations in my profile.  Hopefully it will help my genetic relatives find a match.

Success Stories

Lastly, if you have any success stories using Relative Finder, please leave a comment below or email me.  I’m always looking to highlight success stories or learn more about how an autosomal matching service can help people in their research.

Posted via web from Blaine Bettinger’s Lifestream

Posted via web from Blaine Bettinger’s Lifestream

In the May 2010 issue of Family Tree Magazine, the editors will name the 40 Best Genealogy Blogs.  Last month many of my readers nominated this blog for the list, which I appreciate greatly!

As of today you can vote to narrow down the top 130 nominated blogs to about 80 blogs, which the editors will then reduce to 40.  The blogs have been placed into 10 different categories.  There is more information about the categories and blogs here.

If you have a moment, please feel free to vote for The Genetic Genealogist in the genetic genealogy category!  Voting takes place from October 5th through November 5th, and you can vote as often as you like.  Thank you!

23andMe has been beta testing a new tool for comparing autosomal DNA results called “Relative Finder.” Although I was not one of the beta testers, it seems that this new tool will be of great use to genealogists. Roberta Estes has posted a nice summary of the Relative Finder tool at the “Searching for the Lost Colony DNA Blog.”

90% of Customers Likely to Find a Match!

Relative Finder compares your autosomal SNP results to the results of others in the 23andMe database to determine matches. While developing the tool, 23andMe discovered that in their dataset of “more than 5000 individuals with European ancestry,” 90% of individuals had at least one distant relative between 2nd and 8th degree cousins!

Other Uses

Beyond identifying distant relatives, the tool will potentially have many other uses. For example, one individual has already used SNP testing and comparison of 6 cousins to determine the approximate chromosomal location of an autosomal dominant hereditary condition!

The ASHG Abstract

Below is 23andMe’s abstract for the upcoming 2009 ASHG (American Society of Human Genetics) meeting regarding the Relative Finder tool:

Discovering Distant Relatives within a Diverse Set of Populations Using DNA Segments Identical by Descent.

L. Hon, B.M. Henn, J.M. Macpherson, N. Eriksson, A. Wojcicki, L. Avey, S. Saxonov, J.L. Mountain. 23andMe, Inc, Mountain View, CA.

“Close familial relationships, such a parent-offspring relationships, are inferred readily from genotype and allele frequency data for a limited number of single nucleotide polymorphisms (SNPs) or short tandem repeat (STR) polymorphisms. However, researchers have not focused on accurately inferring the degree of relationship between individuals who share a common ancestor 3-10 generations ago; such inference requires high density genome-wide information not available until recently. In order to characterize relatively distant relationships for a sample, we analyzed the sharing of DNA identical by descent (IBD) in a large database of self-selected individuals of European ancestry, including a subset identified as Ashkenazim. Individuals from more endogamous ethnic populations, such as the Ashkenazim, share on average more DNA identically by descent than do individuals of Asian ancestry or of European ancestry broadly defined. Extensive population level sharing of identical genomic segments complicates the prediction of relationship level for a pair of individuals since identical segments may reflect common ancestry older than the most recent ancestor for a pair of individuals in a pedigree. In order to understand the pattern of the observed population-level sharing, we simulated extended pedigrees using different populations to calculate the expected amounts of sharing for 1st through 10th cousins. Specifically we assessed the relationship between the length of the longest segment and the most recent common ancestor. From the simulations, we also determined bounds for predicted cousinships given a specific amount of segmental sharing. Using these bounds as a guide, we detected at least one distant relative, between 2nd-8th degree cousin, for 90% of individuals in our dataset of more than 5000 individuals with European ancestry. An even higher fraction of our Ashkenazi sample, 99%, had at least one distant relative between 2nd-7th degree cousinship in our dataset.”

Last week my Google alert for “genetic genealogy” went crazy, and it took me a few days to realize that Ancestry Magazine recently made all their archives available for free online.  Although I’m not sure how far back their archives go, there appears to be hundreds of genealogy articles on the site.

A quick search of “DNA” at the site, for instance, reveals MANY articles relating to genetic ancestry testing. This is a great resource for anyone interested in genetic genealogy.

I see that Schelly at Tracing the Tribe had the same Google alerts frenzy last week. As she notes, some of the articles are rather old, so be sure to check the dates before you read them; the information might require some updating!

From a story in today’s Mormon Times:

The first rumblings about DNA and the Book of Mormon came about 10 years ago, according to Perego, a senior researcher at Sorenson Molecular Genealogy Foundation.Critics cobbled together data from a variety of early DNA studies and came to the unsurprising conclusion that the studies indicated an Asian origin for Native Americans.

This, the critics argued, proved that the Book of Mormon was false. They claimed that the book says the continent was empty and if it was empty, then all Native Americans should have Lehi’s Israelite DNA, not Asian DNA.

Ugo Perego, well-known in genetic genealogy circles, talks with the journalist about the compatibility of our current understanding of Native American origins and the Book of Mormon.  According to Perego, there are possibilities solutions to this apparent conundrum:

“Try to ask this question to a population geneticist: ‘Is it possible that a small family from Israel could have arrived in America, to a largely populated continent, and that no genetic evidence would survive after 2,600 years?’” Perego says. “Why don’t they ask that question? That is exactly the question they need to ask.”

Read the article to learn more.

The article is part 1 of a 4-part series.

Posted via web from Blaine Bettinger’s Lifestream

Trends in Genetics has an article by Turi E. King and Mark A. Jobling from the University of Leicester highlighting Y-DNA genetic genealogy.  Specifically, the article – “What’s in a name? Y chromosomes, surnames and the genetic genealogy revolution” – looks at the relationship between surnames and Y-DNA genetics.  Dr. King and Dr. Jobling have previously conducted a great deal of research in this area (see here and here, for example).

The article is a review of this area and contains some interesting information, including a section regarding “Genetic genealogy and the rise of recreational genetics.”

Genetic genealogists recognized as making genuine contributions to the field:

In the article, the authors note that genetic genealogists are making discoveries in this field:

“Genetic genealogy enthusiasts often display an impressive level of knowledge about aspects of molecular evolution, population genetics and statistics; some of this is evinced in the quarterly online Journal of Genetic Genealogy (www.jogg.info). Although it lacks the standard scientific peer-review system of traditional journals, it is nonetheless attracting academic geneticists among its authors and is an interesting model for public involvement in scientific publication. Other resources for genetic genealogy are listed in Box 3. Thanks to the advances in DNA technology and the power of the internet, genetics is now joining astronomy as a science in which amateurs can make useful discoveries.”

From the abstract:

Heritable surnames are highly diverse cultural markers of coancestry in human populations. A patrilineal surname is inherited in the same way as the non-recombining region of the Y chromosome and there should, therefore, be a correlation between the two. Studies of Y haplotypes within surnames, mostly of the British Isles, reveal high levels of coancestry among surname cohorts and the influence of confounding factors, including multiple founders for names, non-paternities and genetic drift. Combining molecular genetics and surname analysis illuminates population structure and history, has potential applications in forensic studies and, in the form of ‘genetic genealogy’, is an area of rapidly growing interest for the public.

HT: Ugo Perego

“I must admit that I have always been a bit embarrassed to admit that I cannot prove the origins of my own surname. I have been researching my family tree for more than thirty years and have found most of my ancestors back into the 1700s with quite a few families traced even further back. Yet there has always been one glaring exception: the origins of my EASTMAN ancestors.”

So begins this interesting article by Dick Eastman (of Eastman’s Online Genealogy Newsletter fame). Dick had researched the brick wall in his paternal line for years without much luck, but recently peered through the brick wall with the help of genetic genealogy.  The answer to his mystery was hiding in every cell of his body.

After learning of Dick’s brick wall, Katherine Hope Borges of ISOGG volunteered to start the Eastman DNA Project to help him and others learn more about the surname. Through that project, Dick learned that he is related to “the others who are known descendants of Roger Eastman, the 1638 immigrant.” Although the exact line of descent is unclear, he is now able to focus his research to save both time and money.

In addition to Dick’s article, Katherine has a write-up of the story at the Southern California Genealogical Society.

Posted via web from Blaine Bettinger’s Lifestream