Investigation of the regulatory hot-spots identified for type 2 diabetes (360G-Wellcome-209106_Z_17_Z)


<p>The complex causal chain between a gene and its effect on susceptibility cannot be unravelled until the casual changes have been localised in the DNA sequence. By exploiting high-resolution population-specific genetic maps, we have recently identified 111 additional disease-susceptibility locations, 93 of which are cosmopolitan (in Europeans and African-Americans) and 18 are European specific. We also refined previously identified T2D signals and showed that many of these are also risk loci in African-Americans. The novelty of our results is two-fold: 1) We obtain a precise location for the implicated functional variant(s) and 2) We were able to identify that the majority of the disease locations appear to confer risk of T2D by acting as expression quantitative trail loci (eQTL) that regulate adipose expression levels of a large number of cis-regulated genes.&nbsp;Our aim is&nbsp;to further characterise in detail all the 111 novel and previously found loci by effectively integrating all&nbsp;our causal location estimates together with cell-specific regulatory annotation and chromatin modifications. In addition, we will investigate all our disease and co-localised eQTL locations for tissue specificity (so far we have only used adipose) by performing gene expression analyses in other tissues relevant to T2D.</p>

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Grant Details

Amount Awarded 99945
Applicant Surname Maniatis
Approval Committee Science Seeds Advisory Panel
Award Date 2017-09-05T00:00:00+00:00
Financial Year 2016/17
Grant Programme: Title Seed Award in Science
Internal ID 209106/Z/17/Z
Lead Applicant Prof Nikolas Maniatis
Planned Dates: End Date 2019-10-31T00:00:00+00:00
Planned Dates: Start Date 2017-12-15T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London