Science and Reason: Disease genes

This is old news (over a month), and it was widely reported in the general media, so I'm sure most readers are aware of it. But it seems important enough to note here, just for the record. It might be considered one of the most important science stories of the year.

Largest Ever Study Of Genetics Of Common Diseases Published

The Wellcome Trust Case Control Consortium, the largest ever study of the genetics behind common diseases such as diabetes, rheumatoid arthritis and coronary heart disease, published its results in the journals Nature and Nature Genetics.

The £9 million study is one of the UK's largest and most successful academic collaborations to date. It has examined DNA samples from 17,000 people across the UK, bringing together 50 leading research groups and 200 scientists in the field of human genetics from dozens of UK institutions. Over two years, they have analysed almost 10 billion pieces of genetic information.

Information about a couple of autoimmune diseases figured prominently in the results.

Amongst the most significant new findings are four chromosome regions containing genes that can predispose to type 1 diabetes and three new genes for Crohn's disease (a type of inflammatory bowel disease). For the first time, the researchers have found a gene linking these two autoimmune diseases, known as PTPN2.

The study has also confirmed the importance of a process known as autophagy in the development of Crohn's disease. Autophagy, or "self eating", is responsible for clearing unwanted material, such as bacteria, from within cells. The may be key to the interaction of gut bacteria in health and in inflammatory bowel disease and could have clinical significance in the future.

"The link between type 1 diabetes and Crohn's disease is one of the most exciting findings to come out of the Consortium," says Professor John Todd from the University of Cambridge, who led the study into type 1 diabetes. "It is a promising avenue for us to understand how the two diseases occur. The pathways that lead to Crohn's disease are increasingly well understood and we hope that progress in treating Crohn's disease may give us clues on how to treat type 1 diabetes in the future."

There were also findings about genetic factors in obesity, type 2 diabetes, and heart disease. In fact, seven major disease in all:

These are bipolar disorder, Crohn's disease, coronary heart disease, hypertension, rheumatoid arthritis and type 1 and type 2 diabetes.

Interestingly, rheumatoid arthritis is also an autoimmune disease. And the immune system (especially in regard to inflammation) probably plays some role in other ailments on this list.

Most readers here probably understand that very seldom is a single gene ever the sole "cause" of a particular disease. Instead, what has been found, in this study and in others, is a number of variants (called alleles) of a variety of genes, where one of more of the variants, if present in an individual, increases the person's risk of eventually developing the disease – conditioned on the presence of other genetic variations, environmental conditions, and so forth. As another account explains:

Sick Genes

[G]enes, although potent predictors, are not always the sole cause of particular diseases. For instance, environmental factors, lifestyle (diet, exercise, etcetera) and exposure to infections can all play roles in determining whether an individual will develop heart disease, for example. "It's about hundreds of genes in your genome contributing a threshold of genetic susceptibility," Todd says. "It's not about one gene."

Nevertheless, on average, having one copy of some of the newly identified genes raises a person's chances of developing one of the seven studied diseases by 20 to 40 percent, and those with two copies face nearly double that risk, researchers say. "What hasn't been clear is exactly which bits of the genome have an effect and which variants make people more [or less] likely to get a disease," Donnelly notes.