Genetic Studies of Melatonin and Its Contribution to Metabolic Traits

Since melatonin is a pineal hormone with a broad variety of functions including mediation of inflammation, immunity, circadian rhythms, and antioxidative defense, it is considered to possibly be involved in the pathogenesis of various conditions. Compelling evidence demonstrate that melatonin levels are associated with sleep and metabolic disorders. Drugs targeting melatonin metabolism have been clinically used for sleep disorders and potentially in metabolic disorders. Therefore, melatonin is among the most important but least understood hormones. Melatonin level is under substantial genetic influence. However, the evidence for loci associated with melatonin level remains unclear. Here, we propose to conduct 1. association studies of circulating melatonin levels with demographic and lifestyle factors (such as sex, age, smoking, drinking,…etc.) and metabolic phenotype including body mass index, waist circumference, fasting glucose, cholesterols, triglycerides, liver enzymes, blood pressures, estimated glomerular filtration rate, uric acid, and the presence of metabolic syndrome, 2. a genome-wide association analysis using SNP genotyping array in 5,000 subjects recruited from general population (Taiwan Biobank), 3. a targeted-region sequencing study to follow up candidate genes from our GWA study, 4. expression studies that assess the association of lead SNPs with corresponding melatonin expression in human adipose tissue, 5. functional analysis of rare melatonin mutations identified by sequencing

Project ID:PC10508-0523
External Project ID:MOST105-2314-B182-062