Nature 2017, Vol 547, pp 173-178

By Mark Daly of Massachusetts General Hospital, Harvard Medical School, and the Broad Institute of MIT and Harvard and 46 of his fellow scientists from Belgium, Denmark, Sweden, Spain, Germany, Australia, UK, Canada, and the Netherlands

The American scientists were supported primarily by NIH, and the Crohn’s & Colitis Foundation of America, 

Inflammatory bowel diseases are chronic gastrointestinal inflammatory disorders that affect millions of people worldwide.Genome-wide association studies have identified 200 inflammatory bowel disease-associated loci, but few have been conclusively resolved to specific functional variants. Here we report fine-mapping of 94 inflammatory bowel disease loci using high-density genotyping in 67,852 individuals. We pinpoint 18 associations to a single causal variant with greater than 95% certainty, and an additional 27 associations to a single variant with greater than 50% certainty. These45 variants are significantly enriched for protein-coding changes (n = 13), direct disruption of transcription-factor binding sites (n = 3), and tissue-specific epigenetic marks (n = 10), with the last category showing enrichment in specific immune cells among associations stronger in Crohn’s disease and in gut mucosa among associations stronger in ulcerative colitis. The results of this study suggest that high-resolution fine-mapping in large samples can convert many discoveries from genome-wide association studies into statistically convincing causal variants, providing a powerful substrate for experimental elucidation of disease mechanisms.

My takeaways:

1. The many authors show that by using this powerful method of genome wide associated studies, scientists can elucidate the underlying mechanism for disease development. Especially in complicated diseases such as inflammatory bowel disease. This has a huge impact for all the other diseases that are not well understood; which are most of the diseases that affect our lives because they have no cures or good treatments.