Founder population-specific weights yield improvements in performance of polygenic risk scores for Alzheimer disease in the Midwestern Amish.
HGG Adv
; 4(4): 100241, 2023 Oct 12.
Article
en En
| MEDLINE
| ID: mdl-37742071
ABSTRACT
Alzheimer disease (AD) is the most common type of dementia and is estimated to affect 6 million Americans. Risk for AD is multifactorial, including both genetic and environmental risk factors. AD genomic research has generally focused on identification of risk variants. Using this information, polygenic risk scores (PRSs) can be calculated to quantify an individual's relative disease risk due to genetic factors. The Amish are a founder population descended from German and Swiss Anabaptist immigrants. They experienced a genetic bottleneck after arrival in the United States, making their genetic architecture different from the broader European ancestry population. Prior work has demonstrated the lack of transferability of PRSs across populations. Here, we compared the performance of PRSs derived from genome-wide association studies (GWASs) of Amish individuals to those derived from a large European ancestry GWAS. Participants were screened for cognitive impairment with further evaluation for AD. Genotype data were imputed after collection via Illumina genotyping arrays. The Amish individuals were split into two groups based on the primary site of recruitment. For each group, GWAS was conducted with account for relatedness and adjustment for covariates. PRSs were then calculated using weights from the other Amish group. PRS models were evaluated with and without covariates. The Amish-derived PRSs distinguished between dementia status better than the European-derived PRS in our Amish populations and demonstrated performance improvements despite a smaller training sample size. This work highlighted considerations for AD PRS usage in populations that cannot be adequately described by basic race/ethnicity or ancestry classifications.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Alzheimer
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Aspecto:
Patient_preference
Límite:
Humans
País/Región como asunto:
America do norte
Idioma:
En
Revista:
HGG Adv
Año:
2023
Tipo del documento:
Article