TCF7L2 Strikes again, This time it's the Finns

The Latest edition of Mendel's Garden is up at Scienceroll. If you haven't seen it, the Gregorian Rap All-Stars video is a must see!

It's official. I can say without any doubt that the gene TCF7L2 is somehow implicated in diabetes. Another whole genome association study was performed and results were published in the American Journal of Human Genetics.

The study which performed because there only exist a handful of genes that have been implicated in the genetics of diabetes. These include PPAR gamma, TCF7L2, KCNJ11, CPN10, FTO. And because GWAS is hot now. They selected 4 populations, all Caucasian. 200 Finns with diabetes and 200 without, similar numbers of Ashkenazi Jews, 100 soccer hooligans from Manchester and 99 affected Brits, as well as 100 Germans with diabetes and another 100 without.

What they found was not surprising. TCF7L2 SNPs rs7903146, rs7901695 and rs122255372 were all replicated as linked again with ORs of 1.6-1.7. They also found several candidate loci. None which were that impressive when attempted to be replicated.

So, what does this all mean? Well it means that there is an increased risk for diabetes if you have any of the aforementioned changes in your TCF7L2 gene. But how does that help us? Now that it is shown to be linked, we need some data on how to prevent diabetes in the carriers of altered TCF7L2.

Does anyone have good data on this?

The Sherpa Says: Sometimes I do eat humble pie. That being said, I will not recommend TCF7L2 testing for anyone. Importantly because there are several SNPs associated, not just the SNP that deCode tests for. There is more to this diabetes story than meets the eye.

This week in NEJM

So I have been reading about how the new article in the New England Journal of Medicine shows that BRCA gene mutations are not worse than sporadic breast cancers due to non-BRCA mutations.

If you look at the article you will see that there are many reasons why this is flawed thinking. But more importnatly it flies in the face of another study which actually showed and increased risk in worse outcomes with BRCA1 mutations.

So on closer inspection what was the NEJM article about?

They took all breast cancer specimens available in Israel's National Healthcare repository and looked for 3 I repeat 3 FOUNDER MUTATIONS....... This immediately makes the study invalid to comparison on women who have non ashkenazi mutations, especially if they are not founder mutations.

Secondly they analyzed outcomes retrospectively. This is a notorious way to get confounding results as well.

Thirdly this study did not have interpretable data regarding estrogen or progesterone receptor status.......This is a big deal!!!

And Lastly,
"We had 16-year follow-up data on mortality and incident cancers, but information on the cause of death was available from the Central Bureau of Statistics only for deaths that occurred before 2000." None from after 2000........

The Gene Sherpa Says: Before bloggers and press go off half cocked in this interpretation we need to be careful in how we evaluate this study. This ONLY means if you are an ashkenazi jew from Israeli heritage and have one of 3 founder mutations, then you are not more likely to have adverse outcomes than ANYONE else who is Israeli and Ashkenazi with non founder mutation breast cancer....That's IT. Nothing else can be extrapolated here. To those who are.....tread carefully...Because you are misleading the public!