Functional Genomics of Cardiometabolic Disease in the Kilpeläinen Group

The research involves four main aims:

1. Identifying shared pathways for cardiometabolic risk variants: the group uses large genome-wide association datasets to identify distinct phenotypic association patterns represented by multiple genetic risk variants and derives hypotheses on the cellular and physiological processes that these patterns represent. These hypotheses are then subjected to further computational and experimental investigation.
2. Mapping the causal variants, genes, cell types, and cellular pathways through which the cardiometabolic disease variants act. The group utilizes molecular data repositories to functionally interpret the genetic associations, with colocalization between cardiometabolic disease associations and molecular trait associations (epigenomic, transcriptomic, proteomic) serving as an anchor for integrating layers of biological information.
3. Relating the computationally derived functional interpretations to key functional readouts in human mesenchymal stem cell and adipocyte cell lines, using both traditional and high-throughput perturbation assays.
4. Identifying new ways to treat cardiometabolic disease, by inhibiting the genetically defined mechanisms of action of disease risk variants in adipose tissue.

"Genetic studies of leptin concentrations implicate leptin in the regulation of early adiposity"
Published in Diabetes in 2020, this study finds that both coding and non-coding variants of the leptin gene are linked to childhood adiposity.

"Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity"
Published in Nature Communications in 2019, this study uses data from >250,000 adults to identify genetic variants for which the effects on lipid levels are modified by physical activity.

"Obesity, unfavorable lifestyle and genetic risk of type 2 diabetes"
Published in Diabetologia in 2020, this study finds that having normal body weight is crucial in the prevention of type 2 diabetes, regardless of genetic predisposition.

List of publications by Tuomas Kilpeläinen