Genome-wide association study to find SNPs associated with circulating levels of the protein FGF-21

Sammanfattning: Colorectal cancer (CRC) is one of the most common types of cancer globally. In Sweden, every year over 6000 individuals are diagnosed with CRC making it the fourth most common form of cancer in the country. The symptoms of the disease occur late in its development, therefore diagnosis is often delayed, which has a negative effect on mortality. Once an individual starts to experience symptoms, a colonoscopy is performed to examine the colon and set a diagnosis. However, colonoscopy is straining for the individual and costly for the health care system. Therefore, a complementary risk screening method is needed to help identify high-risk individuals. Two separate studies have shown that individuals who develop CRC also have increased levels of the fibroblast protein (FGF-21). Thus, there is an interest in potentially using FGF-21 as a risk screening marker in a blood test for filtering out the high-risk individuals of colorectal cancer. However, it is not known whether FGF-21 is part of the causal pathway leading to CRC development or only a marker of increased risk. Therefore, more work is needed to better understand the role of FGF-21 in CRC disease. This study represents the first step in identifying if FGF-21 has any causal role in CRC. To do this I have tried to identify single genetic variants (so-called SNPs) in the human DNA that are associated with circulating levels of FGF-21 by conducting a genome-wide association study (GWAS). The genome and protein data used in the GWAS originated from 131 individuals participating in the Västerbotten Intervention Programme. Preliminary results showed no significant SNPs among the study subjects when correcting for multiple tests at a significance level of 5%. Although there were no significant findings I did find several indications of potential associations and the small size of the dataset might explain why they did not reach significance. The analytical pipeline I have created as part of this project will be used in a larger dataset where it will be possible to both verify potential associations from this study and hopefully identify other interesting SNPs. Any confirmed findings will in the future be used in a Mendelian Randomization study where the association between having SNPs that increase your levels of FGF-21 and the risk of CRC will be assessed. If such an association could be confirmed it would indicate that FGF-21 plays a causal role in CRC development.