UK BioBank study finds 14 genes implicated in common blood disorder

Heritable genetic variants associated with a blood disorder that is a risk factor for leukaemia and heart disease have been identified.

Clonal haematopoiesis (CH) is a condition characterised by the development of blood cell clones in the body, driven by identical mutations in their DNA. It becomes more common with age, and about one in three people will be affected in their lifetime. The condition does not have any symptoms but can increase the risk of cardiovascular conditions such as heart attacks, and some types of blood cancer.

'Our findings implicate genes and the mechanisms involved in the expansion of aberrant blood cell clones and can help guide treatment advances to avert or delay the health consequences of clonal haematopoiesis such as progression to cancer and the development of other diseases of ageing.' said co-lead author Dr Siddhartha Kar from the University of Bristol.

Scientists from the Wellcome Sanger Institute, Cambridge, and the universities of Bristol and Cambridge used blood whole-exome sequencing data from 200,453 UK BioBank participants to identify inherited mutations associated with a predisposition to CH.

Publishing their findings in Nature Genetics, the authors detail 14 inherited genetic mutations associated with CH, ten of which had not been known to be associated with the condition before.

Most of these variants have previously been identified in relation to blood cancers and tumours elsewhere in the body, such as the lungs, prostate, and ovaries. These variants are found in genes implicated in DNA damage repair, haemopoietic stem cell migration, and oncogenesis. Several associations were specific to CH subtypes, suggesting a role in CH development.

The team also found that CH accelerates the process of biological ageing, and established smoking as one of the strongest modifiable risk factors for developing the condition, although the results of this study do not prove a causal relationship.

'We were particularly pleased to see that some of the genetic pathways driving clonal haematopoiesis appear to be susceptible to pharmacological manipulation and represent prioritised targets for the development of new treatments.' noted co-lead author Dr Pedro Quiros, formerly from the Wellcome Sanger Institute, now group leader at the Health Research Institute of Asturias, Oviedo, Spain.

The researchers claim to reveal inherited susceptibility to CH and its implications for human health and ageing, which could hold clinical implications and potential targets for new treatments.