The human genome is a complete set of a person’s DNA. Serving as a blueprint for all cells in the body, the genome contains about 20,000 genes. The first human genome was “sequenced” in 2003, meaning researchers mapped out the order of over 3 billion of the building blocks (nucleotides) that make up human DNA.
Sequencing allows researchers to know which parts of DNA contain genes and to find changes in individual genes that cause a disease. For example, a rare, familial form of early-onset Alzheimer’s disease is caused by a genetic mutation that is passed on from parent to child. Other genetic variations which are more common only increase a person’s risk of a disease, not actually cause the disease.
The first large-scale genome-wide association study was recently completed in people with dementia with Lewy bodies. Led by Drs. Rita Guerreiro and Jose Bras of the UK Dementia Research Institute at UCL, this study was done in two phases to discover and then validate genetic changes associated with DLB. With the help of 22 centers in 10 countries, researchers analyzed samples from 1,743 people with DLB and 4,454 healthy controls, all white and of European descent. One of the strengths of this study was that 76% of the DLB cohort had autopsy confirmation of their clinical diagnosis.
The findings confirmed previously reported associations of variations in three genes that increase the risk of a person developing DLB. Those genes are APOE, SNCA and GBA. One of the interesting findings was that although the SNCA gene had also been associated with Parkinson’s disease, the association with DLB seemed to be on a different part of the gene. This suggests that the way in which the gene is involved in each disease might be different. A new gene, CNTN1, was also identified as one that may increase risk of DLB; further study is needed to replicate this finding.
The study also looked at other two genetic variations flagged in earlier studies as possible genetic risk factors for DLB, which are also highly associated with Alzheimer’s disease (TREM2) or Parkinson’s disease (MAPT). Neither reached genome-wide significance however in this study.
In total these findings resulted in an estimate heritability of 36% for DLB in this cohort. This means the proportion of risk for developing DLB based on these individuals’ unique genetic makeup was an estimated 36%. The other 64% could be due to environmental factors or other genetic variations yet to be identified. This study adds weight to the meaningful role genetics play in DLB. Further research is needed in cohorts with greater racial and ethnic diversity to more fully understand the role of genetics in DLB.
This study was first published online in December, 2017 in Lancet Neurology. Funding was provided by the Alzheimer’s Society and the Lewy Body Society in the UK.