Discovery of genetic variants linked to Alzheimer’s offers hope for cure

By James Gamble via SWNS

Genetic variants linked with Alzheimer's have been identified by scientists - offering new hope of a cure for the disease.

Researchers identified 17 genetic variants that may influence the risk of people developing Alzheimer’s, which is the most common form of dementia and affects more than 55 million people across the globe.

The breakthrough, discovered using whole genome sequencing, identified 17 significant variants associated with Alzheimer’s disease in five genomic regions.

Scientists say the discovery could lead to treatment and prevention methods for the neurodegenerative disease.

Alzheimer’s is the fifth leading cause of death among people aged 65 and older in the US and currently affects more than six million Americans - a number expected to rise sharply to nearly 13 million by 2050.

Alzheimer's and other forms of dementia affect over 920,000 Britons, a figure that will reach two million by 2050. Worldwide, cases will triple beyond 150 million.

The study, published in the Alzheimer's Association's journal Alzheimer’s & Dementia,
has enabled researchers to pinpoint rare and important genes and variants, building upon genome-wide association studies that focus solely on common variants and regions.

Dr. Anita DeStefano, a professor of biostatistics at Boston University School of Public Health (BUSPH) and a co-senior author of the study, explained: "Prior genome-wide association studies using common variants have identified regions of the genome, and sometimes genes, that are associated with Alzheimer’s disease.

“Whole genome sequence data interrogates every base pair in the human genome and can provide more information about which specific genetic change in a region may be contributing to Alzheimer’s disease risk or protection.”

The BUSPH team conducted single variant association analyses and rare variant aggregation association tests using whole genome sequencing data from the Alzheimer’s Disease Sequencing Project (ADSP), a genetics initiative that the National Institutes of Health developed in 2012 as part of the National Alzheimer’s Project Act’s goal to treat and prevent the disease.

The ADSP data included more than 95 million variants among 4,567 participants with or without the disease.

Among the 17 significant variants linked with Alzheimer’s disease, a variant called KAT8 was one of the most notable, as it was associated with the disease in both the single and rare variant analyses.

The researchers also found associations with several rare variants called TREM2 variants.

Dr. Chloé Sarnowski, assistant professor in the Department of Epidemiology at UTHealth Houston School of Public Health and a co-lead author of the study, said their methods allowed the researchers to decipher whether associations were shared across different ethnographic populations.

“By using whole genome sequencing in a diverse sample, we were able to not only identify novel genetic variants associated with Alzheimer’s disease risk in known genetic regions, but also characterize whether the known and novel associations are shared across populations,” she said.

The ADSP includes ethnically diverse participants, with the population-specific assessments focusing on White/European-ancestry, Black/African-American, and Hispanic/Latino subgroups, as well as a multi-population meta-analysis.

Historically, Black and Latino populations have been underrepresented in genetic studies of Alzheimer’s disease, despite having a higher prevalence of the disease than other ethnic groups.

“Including participants that represent diverse genetic ancestry and diverse environments in terms of social determinants of health is important to understanding the full spectrum of Alzheimer’s disease risk, as both the prevalence of the disease and the frequencies of genetic variants can differ among populations,” Dr. DeStefano added.

She added that the sample sizes in the population-specific analyses were small, meaning the team had limited ability to detect associations: “We replicated known population differences for the APOE gene, which is one of the best-known and strongest risk genes for Alzheimer’s disease.”

In future studies, the researchers hope to examine the population-specific variants they identified in much larger sample sizes, as well as explore how these variants affect biological functioning.

“We are currently working on expanding this research to be able to use whole genome sequencing with larger sample sizes in the ADSP to be able to look at the full array of genetic variants, not only within known Alzheimer’s disease genetic regions but across the whole genome,” added co-senior author Dr. Gina Peloso, an associate professor of biostatistics at BUSPH.