Somatic Mosaicism and Alzheimer’s Disease Risk

Earlier this year, Dr. Chunyu Liu’s team shared data from the Somatic Mutations in Brains of Alzheimer’s Disease (SMIB-AD) study through the AD Knowledge Portal’s newly established Community Data Contribution Program (CDCP). Sharing the data was important to the team as a way to encourage data validation and novel re-use.

The SMIB-AD Study provides RNA sequencing, bulk and single-cell whole genome sequencing, and bulk whole exome sequencing across 33 individuals diagnosed with either Alzheimer’s disease (AD), or no cognitive impairment (NCI).

Chunyu Liu

“We wanted to know why some people are more vulnerable to Alzheimer’s disease than others,” said Liu, a professor of psychiatric and neuroscience at SUNY Upstate Medical University. Liu and his collaborators began to search for molecular changes that could be responsible for this vulnerability. The team included Drs. Elliot S. Gershon, of University of Chicago, Geoffrey Faulkner, of University of Queensland, and David Wesley Craig, of University of Southern California.

After securing funding from the National Institute on Aging (NIA), the group analyzed brain tissue to look for somatic mutations, which are DNA changes that take place after fertilization. Their analysis sought to identify differences in somatic variants in the brain between AD and NCI individuals. They performed whole genome sequencing, whole exome sequencing, captured sequencing, and single-cell whole genome sequencing on the brain and liver tissues of the same donors.

Based on this data, they discovered burdens of non-coding somatic mutations in AD brains and rejected the hypothesis that AD brains had excessive somatic mutations in APP or other early-onset AD genes. Understanding that such findings need to be replicated by independent samples and different methods, Liu decided to make the data available to the research community in hopes that sharing it as part of a larger AD resource might increase its utility.

An initial contributor to the NIMH-funded psychENCODE consortium, Liu already had experience in open data sharing. He was familiar with the AD Knowledge Portal, and knew the advantages of working in a collaborative scientific community. He discovered CDCP, and volunteered to share SMIB-AD study data.

“I don’t like to do ‘secret research.’ Secret research is a roadblock for science.”

CDCP was launched in the fall of 2020 and lets investigators outside of the AD Knowledge Portal funded programs share data and resources through the Portal. Researchers can then leverage these resources, working toward validation, replication, or data re-use. The program aims to complement datasets already available on the AD Knowledge Portal. These resources will fill an unmet need to accelerate the study of brain aging, Alzheimer’s disease, and related dementias.

The CDCP facilitates open science, which allows the scientific community to examine new hypotheses and explore different angles. 

“We have been open from the beginning,” Liu said, “because I don’t like to do ‘secret research.’ Secret research is a roadblock for science.”