The Medical Genome Reference Bank (MGRB) is planned to contain the whole genome sequences (WGS) of over 4000 elderly individuals with no reported history of cancer, cardiovascular disease, or neurodegenerative diseases until at least age 70.
The study design, which was previously published, curates samples from two previous studies, the ASPirin in Reducing Events in the Elderly (ASPREE) and Sax Institute 45 and Up Study. The MGRB, with corresponding author David M. Thomas of the Garvan Institute of Medical Research, Sydney, Australia, has now published the first summary release of 2570 participant’s genomic and phenotypic data in the journal Nature Communications.
The MGRB aims to contribute to the field of healthy aging by quantifying any genetic associations with old age without noncommunicable disease and maintenance of well-being. One of the initial novel findings of the study is that mitochondrial copy number correlates with grip strength, but only in men.
As well as providing a wealth of information about healthy aging, the data bank could also serve as a useful for control for studies of disease in the elderly. For example, the use of the MGRB as a control cohort for prostate cancer risk reduced the sample size required for significance by approximately 25% in comparison with the UK biobank.
Genetic variants linked to childhood diseases were absent in the healthy elderly cohort. Overall, the population did not contain many cancer related variants compared to cancer patients. As expected, 7.2% of participants showed evidence of clonal haematopoiesis of indeterminate potential (CHIP). There was a lack of variants linked to cardiovascular disease, and neurodegenerative disease.
Interestingly, 1.1% of healthy individuals carried dominantly acting variants linked to disease, but no symptoms. Some individuals harbored pathogenic variants in BRCA2, MSH2, or PMS2, but had no personal histories of breast or colorectal cancer. Likewise, there were mutations in DSG2, DSP, KCNH2, KCNQ1, MYBPC3, MYL3, and SCN5A but no evidence of cardiac arrest or stroke. There were APOB carriers that did not have elevated blood lipid levels.
The authors conclude that “particularly with respect to cancer, the DNA-based measures of biological age we have demonstrated here may represent an individual’s underlying mutation rate, and therefore true cancer risk, due to combined genetic and environmental factors.”