A large study including genetic sequence data from participants of four different study cohorts, two of which include a high proportion of people with non-European ancestry, has uncovered 16 new points of variation in the genome linked to Alzheimer’s disease.
Alzheimer’s disease affects 315 million people around the world, which corresponds to approximately 22% of people over the age of 50 years. The disease is more prevalent among individuals who identify as non-Hispanic Black versus non-Hispanic White and is estimated to be 70% heritable based on past research. “Yet, results obtained in these populations are limited,” say researchers from Massachusetts General Hospital who led the study.
Overall, 49,149 cases (12,074 clinically diagnosed patients and 37,075 who had Alzheimer’s disease-by-proxy) and 383,225 controls were included in the current study. The participants were sourced from the National Institute on Aging Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS), the National Institute of Mental Health, UK Biobank, and All of Us cohorts.
“While larger datasets from biobanks, such as UK Biobank, contain a limited number of confirmed… disease cases, recent studies have increased sample size by using an Alzheimer’s disease-by-proxy phenotype… based on family history, such as those with a first-degree affected family member, or in some cases, even affected grandparents with Alzheimer’s disease, as cases,” explained the authors of the article published in Alzheimer’s & Dementia.
Dmitry Prokopenko, PhD, and Rudolph Tanzi, PhD, both based at the Genetics and Aging Research Unit and the McCance Center for Brain Health at Massachusetts General Hospital, led the current study, which used existing genetic data from the different cohorts to search for genetic variation linked to Alzheimer’s disease.
Of the four cohorts, diversity data was available for the three largest, namely, the UK Biobank (159,629 cases and controls), NIAGADS (25,660 cases and controls), and the All of Us cohort (244,838 cases and controls). The UK Biobank is 93.3% comprised of people of European ancestry, whereas NIAGADS includes 49.3% and All of Us 46.5% individuals with a non-European ancestry.
By-proxy disease cases were only included from the UK Biobank (25,785 individuals) and All of Us (11,290 individuals) cohorts.
Overall, considering clinically diagnosed Alzheimer’s alone, 14 new sites of Alzheimer’s linked genetic variation were found, five common and nine rare. When by-proxy cases of the disease from the UK biobank and All of Us were also included, two additional rare points of variation were observed, which were also of nominal significance in the NIAGADS cohort of real Alzheimer’s cases (10,565 cases).
“We were pleasantly surprised to have made this discovery by expanding genetic analyses beyond populations of European ancestry to more diverse populations,” said co-senior author Tanzi, in a press statement. “We hope this will lead to more accurate predictions of Alzheimer’s disease risk and to new pharmacological and biological targets for treatment and prevention in populations with various ancestries.”
