Browsing by Subject "GWAS"

Seasonal variation has affected human societies throughout history, shaping various aspects of life including agriculture, migration patterns and culture. This influence is observed, among others, in the occurrences of diseases such as viral and bacterial infections, cardiovascular disease and mental disorders. While there are a multitude of factors influencing the timing of disease diagnoses, environmental and behavioral, the genetic role has not been explored to the best of our knowledge. The aim of this thesis was to relate genetic variation to seasonal disease risk. To achieve this, the seasonality of 1,759 disease endpoints was assessed in the Finnish population. A subset of 14 diseases were selected and used as input into a statistical modeling framework that was developed to search for genetic variants associated with seasonal disease risk in the FinnGen study population. A total of 9 genome-wide significant loci affecting seasonality were identified, including a top-sQTL, rs41273830[T], in ITGB8 for major depression and a stop-gain variant, rs601338[A], in FUT2 for intestinal infections, the latter also being protective against disease risk. This introduces a new aspect to genetic research, which can both contribute to better understanding how known disease variants affect disease but also finding new disease variants whose effects are currently obscured by seasonal variation.

Triglycerides are a type of lipid that enters our body with fatty food. High triglyceride levels are often caused by an unhealthy diet, poor lifestyle, poorly treated diseases such as diabetes and too little exercise. Other risk factors found in various studies are HIV, menopause, inherited lipid metabolism disorder and South Asian ancestry. Complications of high triglycerides include pancreatitis, carotid artery disease, coronary artery disease, metabolic syndrome, peripheral artery disease, and strokes. Migration has made Singapore diverse, and it contains several subpopulations. One third of the population has genetic ancestry in China. The second largest group has genetic ancestry in Malaysia, and the third largest has genetic ancestry in India. Even though Singapore has one of the highest life expectancies in the world, unhealthy lifestyles such as poor diet, lack of exercise and smoking are still visible in everyday life. The purpose of this thesis was to introduce GWAS-analysis for quantitative traits and apply it to real data, and also to see if there are associations between some variants and triglycerides in three main subpopulations in Singapore and compare the results to previous studies. The research questions that this thesis answered are: what is GWAS analysis and what is it used for, how can GWAS be applied to data containing quantitative traits, and is there associations between some SNPs and triglycerides in three main populations in Singapore. GWAS stands for genome-wide association studies designed to identify statistical association between genetic variants and phenotypes or traits. One reason for developing GWAS was to learn to identify different genetic factors which have an impact on significant phenotypes, for instance susceptibility to certain diseases Such information can eventually be used to predict the phenotypes of individuals. GWAS have been globally used in, for example, anthropology, biomedicine, biotechnology, and forensics. The studies enhance the understanding of human evolution and natural selection and helps forward many areas of biology. The study used several quality control methods, linear models, and Bayesian inference to study associations. The research results were examined, among other things, with the help of various visual methods. The dataset used in this thesis was an open data used by Saw, W., Tantoso, E., Begum, H. et al. in their previous study. This study showed that there are associations between 6 different variants and triglycerides in the three main subpopulations in Singapore. The study results were compared with the results of two previous studies, which differed from the results of this study, suggesting that the results are significant. In addition, the thesis reviewed the ethics of GWAS and the limitations and benefits of GWAS. Most of the studies like this have been done in Europe, so more research is needed in different parts of the world. This research can also be continued with different methods and variables.