Researchers from the Lieber Institute for Brain Development in Baltimore show that having African ancestry can influence the way genes are expressed in the brain and may explain differences in prevalence of conditions such as Alzheimer’s and Parkinson’s disease between people with African ancestry and other populations.
Writing in Nature Neuroscience, the authors explain that while they did find evidence linking genetic ancestry with differences in the prevalence of disorders such as Alzheimer’s, Parkinson’s and stroke, they did not find evidence linking genetics with psychiatric disorders and behavioral traits, such as schizophrenia and depression.
Research resources to study brain disorders include genome wide association studies (GWAS) or neurological disorders and biobanks containing brain tissue donated by people who have died. However, these resources are mostly based on people of White European origin and lack sufficient contributions or donations from African Americans and other non-White European populations.
The BrainSeq Consortium involves seven pharmaceutical companies and the Lieber Institute for Brain Development. It has tried to remedy the lack of Black American samples in brain research databases and includes 784 samples donated by 587 Black American individuals.
The African Ancestry Neuroscience Research Initiative was recently founded, also aiming to address this gap, and the current study is the first to come out of the initiative.
“This landmark work enriches our understanding of the role of genetic ancestry in the brain, opens new avenues for the development of ancestry-aware therapeutics and paves the way for more equitable personalized medicine,” said senior author Daniel Weinberger, Director and CEO of the Lieber Institute, in a press statement.
The study looked at samples from deceased individuals with some degree of African ancestry (from the Lieber Institute sample collection) who had healthy brains at the time of death. It looked at how genetic ancestry influences gene expression and DNA methylation, a sign of environmental influence, in the brain.
The team calculated that African ancestry could explain up to 26%, 27%, and 30% of heritability for ischemic stroke, Parkinson’s disease, and Alzheimer’s disease, respectively. Stroke and Alzheimer’s disease are seen at a high prevalence in African Americans compared with other populations, but Parkinson’s disease is less common in people with African ancestry.
The researchers also saw signs that many immune-related traits could differ depending on genetic ancestry, but not psychiatric traits. The researchers also assessed epigenetic contribution to disease differences, influenced by the environment and measured using methylation on the DNA, and estimated that around 15% of population differences in gene expression could be linked to epigenetics.
“We leveraged genetic diversity within an admixed population to limit environmental confounders, resulting in converging evidence of the immune response in genetic ancestry-associated transcriptional changes in the brain,” conclude the authors.
“The research we have provided substantively furthers our understanding of the contribution of genetic ancestry in the brain, opening new avenues to the development of ancestry-aware therapeutics and paving the way for equitable, personalized medicine.”
