Largest genetic sequencing study of human disease completed

Researchers have completed the largest sequencing study of human disease to date, investigating the genetic basis of six autoimmune diseases, including diabetes.
The exact cause of these diseases - autoimmune thyroid disease, celiac disease, Crohn's disease, psoriasis, multiple sclerosis and type 1 diabetes - is unknown, but is believed to be a complex combination of genetic and environmental factors.
In each disease only a proportion of the heritability is explained by the identified genetic variants. The techniques used to date, have generally identified common variants of weak effect.
In this study, using high-throughput sequencing techniques, scientists sought to identify new variants, including rare and potentially high risk ones, in 25 previously identified risk genes in a sample of nearly 42,000 individuals.

It has been suggested - in the 'rare-variant synthetic genome-wide association hypothesis' - that a small number of rare variants in risk genes are likely to be a major cause of the heritability of these conditions.
However, the study published in the journal Nature, suggests that the genetic risk of these diseases more likely involves a complex combination of hundreds of weak-effect variants which are each common in the population.

Researchers estimate that rare variants in these risk genes account for only around three per cent of the heritability of these conditions that can be explained by common variants.
"These results suggests that risk for these autoimmune diseases is not due to a few high-risk genetic variations but seems rather due to a random selection from many common genetic variants which each have a weak effect," David van Heel, lead author of the study, said.

"For each disease there are probably hundreds such variants and the genetic risk is likely to come from inheriting a large number of these variants from both parents. If this is the case then it may never be possible to accurately predict an individual's genetic risk of these common autoimmune diseases.
"However, the results do provide important information about the biological basis of these conditions and the pathways involved, which could lead to the identification new drug targets," said van Heel.