Since most diseases have a genetic component, scientists led by the Garvan Institute of Medical Research are analyzing genetic information to determine what keeps us healthy. The team reported that it has compiled a genome reference database of thousands of healthy older Australians, which has the potential, they say, to predict disease-linked gene variants more accurately than has been previously possible.
The scientists released the first genomes of the Medical Genome Reference Bank (MGRB) and published their analysis (“The Medical Genome Reference Bank contains whole genome and phenotype data of 2570 healthy elderly”) in Nature Communications. The MGRB is a collaboration led by Garvan, Monash University’s ASPREE study, and the Sax Institute’s 45 and Up Study.
“Population health research is increasingly focused on the genetic determinants of healthy aging, but there is no public resource of whole genome sequences and phenotype data from healthy elderly individuals. Here we describe the first release of the MGRB, comprising whole genome sequence and phenotype of 2,570 elderly Australians depleted for cancer, cardiovascular disease, and dementia. We analyse the MGRB for single-nucleotide, indel and structural variation in the nuclear and mitochondrial genomes,” the investigators wrote.
“MGRB individuals have fewer disease-associated common and rare germline variants, relative to both cancer cases and the gnomAD and UK Biobank cohorts, consistent with risk depletion. Age-related somatic changes are correlated with grip strength in men, suggesting blood-derived whole genomes may also provide a biologic measure of age-related functional deterioration. The MGRB provides a broadly applicable reference cohort for clinical genetics and genomic association studies, and for understanding the genetics of healthy aging.”
“By doing a comprehensive analysis of healthy individuals, we can get a much clearer understanding of which genes are and which are not linked to disease. The Medical Genome Reference Bank will provide an ideal background for the future of genomic research in Australia,” said David Thomas, PhD, Garvan cancer research theme leader and director of the Kinghorn Cancer Centre.
The authors of the current paper published the genomic data of 2,570 healthy older Australians (64–95 years old) that were free from cancer, cardiovascular disease, or neurodegenerative disease until the age of at least 70. These individuals were participants of the ASPREE study and the 45 and Up Study.
“This first release of data from the Medical Genome Reference Bank gives researchers a much more statistically powerful framework to identify new disease-causing gene variants,” noted Thomas. “For instance, when we analyzed genomes of prostate cancer patients, we found that using the MGRB as a ‘control’ gave us a 25% higher predictive power of disease-linked gene variants than another genome database that is commonly used by researchers to find such variants.”
Using whole genome sequencing, the researchers were able to detect genetic changes associated with aging, including shorter telomeres and less mitochondrial DNA. The scientists also found that the amount of mitochondrial DNA was associated with a higher grip strength in men.
“We were able to detect changes in the genomes that could distinguish between healthy older individuals that share the same age but have different physical function. This indicates that the DNA in an individual’s blood sample may provide a better indicator of their ‘biological age’ than their chronological age,” continued Thomas. “The ability to derive a measure of biological age may better predict health outcomes for individuals. As our population ages, understanding the genetic basis for healthy aging will become more and more important.”
The first release of the data is available to researchers via the Vectis platform. Once completed, the Medical Genome Reference Bank will contain genomic data from over 4,000 older Australians.
