Skip to main content
Premium Trial:

Request an Annual Quote

Genetic Loci Linked to Brain Aging Features

NEW YORK (GenomeWeb) – The genetic loci that influence age-related epigenetic marks in the human brain may overlap with parts of the genome uncovered in several past disease studies, according to a new study.

Researchers from the US and the UK took a genome-wide association study approach to finding genetic variants influencing DNA methylation marks implicated in brain aging or neuronal proportion, using almost 1,800 postmortem brain samples from 1,163 individuals of European ancestry. After narrowing in on suspicious loci, they used transcriptomic data and findings from prior age-related GWAS to refine the set of proposed epigenetic aging-related loci.

The team's results, appearing online this week in Nature Communications, revealed some genetic overlap between at least some of the newly identified loci with sites previously linked to age-related macular degeneration and a range of metabolic, cognitive, inflammatory, and psychiatric conditions.

"The biological relevance of these finding is supported by our findings that both biomarkers of brain aging relate to a host of age-related phenotypes according to GWAS results," corresponding author Steve Horvath, a human genetics researcher at the University of California, Los Angeles, and his colleagues wrote. The study "elucidates the genetic architecture of epigenetic and neuronal aging rates in human brain regions," they noted.

For their analyses, the investigators brought together SNP genotyping data for 1,163 individuals of European ancestry who died between the ages of one- and 108-years old and were profiled for seven prior studies. The genotyping data were considered alongside methylation patterns at more than 350 cytosine methylation marks implicated in brain aging in 1,796 postmortem samples, representing up the prefrontal cortex regions, cerebellum, frontal cortex, pons, and/or temporal cortex.

The team also tallied the proportion of neurons relative to other brain cell types in the samples, since past studies suggest the relative representation of neurons tends to climb with brain age as the proportion of glial support cells drops off.

Indeed, the authors noted that their results pointed to a "highly significant negative correlation between epigenetic age and the proportion of neurons in the [prefrontal cortex]." And in individuals with Alzheimer's disease, they wrote that advancing disease coincided with enhanced age-related methylation "but only after adjusting for the proportion of neurons."

On the GWAS side, the team's search for variants influencing epigenetic brain aging within and across the five brains regions led to loci on chromosome 17 and chromosome 1. Meanwhile, loci on chromosomes 10 and 12 showed ties to the proportion of neurons present in these brain regions.

To start digging into the biological pathways and processes behind these GWAS hits, the researchers added in transcriptomic data for more than 1,700 of the postmortem brain samples, along with expression and expression quantitative trait locus clues from consortium studies. At the brain age-related locus on chromosome 17, for example, they saw variants that appeared to influence expression of genes such as EFCAB5, a gene found at higher levels in samples showing apparent delays in brain aging.

When they focused on neuronal proportion patterns and variants linked to brain age-related features in the prefrontal cortex, the researchers uncovered overlap between these features and those already described in 21 traits or conditions. For example, the authors noted that "gene sets identified by our GWAS of epigenetic aging in the [prefrontal cortex] were significantly enriched with genes associated with cognitive decline, dementia, Alzheimer's disease, and age of [Huntington's disease] onset."

The Scan

Panel Recommends Pfizer-BioNTech Vaccine for Kids

CNN reports that the US Food and Drug Administration advisory panel has voted in favor of authorizing the Pfizer-BioNTech SARS-CoV-2 vaccine for children between 5 and 11 years old.

Sharing How to Make It

Merck had granted a royalty-free license for its COVID-19 treatment to the Medicines Patent Pool, according to the New York Times.

Bring it Back In

Bloomberg reports that a genetic analysis has tied a cluster of melioidosis cases in the US to a now-recalled aromatherapy spray.

Nucleic Acids Research Papers on SomaMutDB, VThunter, SCovid Databases

In Nucleic Acids Research this week: database of somatic mutations in normal tissue, viral receptor-related expression signatures, and more.