As the director of Britain’s Wellcome Trust Center for Human Genetics, Peter Donnelly oversees research that provides vital raw material for the 23andMe Personal Genome Service™ — specifically, correlations between one-letter DNA variations, known as SNPs, and particular diseases.

Those correlations are made by research projects known as genome-wide association studies (GWAS), which scan the genomes of people with a disease and similar individuals who don’t, then look for statistically significant genetic differences between the two groups. The studies can be enormous — last year the Wellcome Trust published the results of a GWAS that analyzed data from 17,000 participants and found genetic associations with seven different diseases — coronary heart disease, type 1 diabetes, type 2 diabetes, rheumatoid arthritis, Crohn’s disease, bipolar disorder and hypertension.

In a commentary published this week by Nature, Donnelly assessed what GWAS have been able to achieve so far, and argued that in most cases, people should be able to gain valuable information from having access to their own genomes.

Here’s Donnelly’s reasoning in his own words:

For a particular disease, most individuals will have inherited some sequence variants that confer risk and some variants that provide protection, and they will therefore have an overall risk around average. A small proportion of people, however, will have inherited mainly variants that confer risk of developing the disease. Using Crohn’s disease as an example … the top 5% of the UK population … have a 5—8-fold higher risk than average of developing the disease, whereas the top 1% have a 9—15-fold higher risk.

Using statistics from the US, that amounts to a risk increase from the poplation average of less than 0.5% to somewhere in the neighborhood of 4-7%. Performing the same calculations for type 2 diabetes, Donnelly concludes that 1% of the population would end up having a 4-fold risk increase, which amounts to about a 50/50 chance of developing the disease.

“Across 50 diseases,” Donnelly continues (23andMe provides complete estimates of lifetime genetic risk due to known SNPs for 10 common diseases),

making the simplifying assumption that susceptibility to each disease is independent of susceptibility to every other disease, almost everyone will be in the top 5% of risk for at least one disease, and nearly half of all people will be in the top 1% for at least one disease. … Given that it is possible to reduce the risk of developing certain diseases, I can see the value of knowing about the genetic risks now.

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A large international collaboration of researchers has tripled the number of SNPs associated with Crohn’s disease, an inflammatory bowel disease that affects about 500,000 Americans. Their results were published online Sunday in Nature Genetics.

Data from more than 16,000 people with European ancestry – 8,059 from a combination of three previously published reports, a new set of 2,325 patients and 1,809 control subjects, and a group of 1,339 families – identified 21 new SNPs associated with Crohn’s disease and confirmed 11 previously implicated SNPs.

(See the table at the end of this post for SNP details).

Although many of the SNPs described in the report only slightly impact the risk of developing Crohn’s, the findings could be important in helping researchers understand the basic biology of the disease.

“Studies such as this are not about developing diagnostic tests, but about identifying targets for new drug therapies. Crohn’s disease can be a very serious condition, often requiring surgery, and the sooner we can understand the underlying causes, the sooner we will be able to devise new treatments to help our patients,” said study author Dr. Miles Parkes.

Some of the newly identified SNPs are in (or near) genes linked to diseases other than Crohn’s, including type 1 diabetes, arthritis, psoriasis, and asthma. This highlights “the important relationships between different diseases and, as such, may offer valuable insights into the pathways that lead to common symptoms such as inflammation,” said Dr. Mark Walport, director of the Wellcome Trust, one of the funding agencies that supported the study.

The researchers suspect there are many more genetic associations left to find for Crohn’s disease.

“These [SNPs] explain only about a fifth of the genetic risk, which implies that there may be hundreds of genes implicated in the disease, each increasing susceptibility by a small amount,” said the study’s lead author, Jeffrey Barrett.

23andMe customers can check their data for many of the SNPs found by Barrett et al. using Browse Raw Data. Here we list 23 out of the 32 SNPs detailed in the report –six SNPs that are already used in the My Gene Journal (now called Health and Traits) Crohn’s disease article have been omitted, as have three SNPS that are not currently available from 23andMe’s service.

Out of a possible total of 46, 80% of people will have between 17 and 25 copies of the riskier versions of these SNPs. Because there are so many of these SNPs – and because the riskier versions are often more common than their less risky counterparts – even people at the high end of the distribution are not much more likely than average to develop Crohn’s disease.

“Effect” is the increase in odds of developing Crohn’s disease conferred by each copy of the riskier version of a SNP. SNPs where we are providing a proxy for the SNP originally reported in the paper are marked with an asterisk.

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