Assessment of pleiotropic disease associations of haplotypes that possess special features

The aim of this research is to assess whether a specific region of human genome that has certain unusual features is associated with risks of multiple diseases that are seemingly unrelated. In a group of adult survivors of childhood cancer, we have observed such associations. Specifically, we have identified a specific region of human genome with the unusual features and detected that people with different genomic patterns of this region have different levels of risk for many human diseases including cancer, cardiovascular diseases, neurological diseases, and musculoskeletal diseases. Such an association of a single genomic region with multiple (disease) conditions is called “pleiotrophy” in genetics and, if confirmed, it has many important implications on both a) biological/genetic understanding of human genome and its evolution and b) clinical etiology and potential treatment strategies of the associated diseases: both of these are potentially of very high public health impact. However, the size of the childhood cancer survivor cohort was small (~2500) and the associations we could detect were limited by the small sample size. Also, it was a cancer survivor population and whether the observed associations in that special clinical population apply to the general population is unknown and requires further investigation. We, therefore, would like to utilize the much larger UK Biobank population data and examine the associations we previously observed as well as other potential associations that we could not examine with adequate statistical power (Aim 1). We will also extend the analysis to other regions of the human genome that have the similar special features (Aim 2). The expected duration of the proposed study is 24 months.