Approved Research

The genetics of rare and common human diseases and traits: Focus on diseases with high impact on morbidity and premature sudden death and forensically relevant human traits

Lay summary

Aim: This project will identify novel genetic causes of rare and common human diseases and traits. The focus will be on sudden death, cardiac, metabolic, psychiatric diseases and externally visible characteristics (EVCs), including biogeographic ancestry and hair and skin colour.

Scientific rationale: Cardiac, metabolic and psychiatric diseases are diseases with high impact on morbidity and premature sudden death in the world. Sudden deaths are cardiac related and the majority are potentially caused by underlying inherited diseases when the patient is less than 50 years old. Many years of extensive research have revealed that both rare and common variants are important players in the disease development and prognosis, but there is a need to further understand the mechanisms underlying these diseases. Therefore, we will use the data in the UK Biobank and combine the genetic data with the impressive data on disease, medication, and lifestyle in the database. We will also focus on the genetics of common human traits, including the EVCs. These are some of the most striking features of an individual and is often used to describe an individual. Certain phenotypes as red hair and pale skin are major risk factors for certain diseases including skin cancers. In addition, the underlying genetics of the pigmentary traits are important for UV-induced vitamin D production and may be more important for vitamin D production than the actual skin pigmentation. Furthermore, vitamin D deficiency has been associated with cardiac diseases and it is also well-known that different ethnic groups with different skin colours have different risks of cardiovascular diseases. Skin colour is complex as many genes with minor effects are involved. To elucidate the complex etiology of skin colour, a large dataset with the relevant metadata is needed.

We plan to utilize the UK biobank data the next fifteen years. We will begin with a project on cardiac heart genes and mortality and continue with the other genotypes and traits mentioned above depending on what we and other research groups publish in the coming years.

Public health impact: The results will provide important and non-redundant knowledge into the understanding of the physiology and pathophysiology of the heart, and contribute to new diagnostic and prognostic principles, to reduce the burden of sudden death from these diseases. A better understanding of the underlying genetics of EVCs, including skin colour may be important to understand certain disease conditions, including cardiovascular diseases and skin cancers.