Rare-variant and polygenic analyses of amyotrophic lateral sclerosis in the French-Canadian genome.
Genet Med
; 26(1): 100967, 2024 Jan.
Article
en En
| MEDLINE
| ID: mdl-37638500
ABSTRACT
PURPOSE:
The genetic etiology of amyotrophic lateral sclerosis (ALS) includes few rare, large-effect variants and potentially many common, small-effect variants per case. The genetic risk liability for ALS might require a threshold comprised of a certain amount of variants. Here, we tested the degree to which risk for ALS was affected by rare variants in ALS genes, polygenic risk score, or both.METHODS:
335 ALS cases and 356 controls from Québec, Canada were concurrently tested by microarray genotyping and targeted sequencing of ALS genes known at the time of study inception. ALS genome-wide association studies summary statistics were used to estimate an ALS polygenic risk score (PRS). Cases and controls were subdivided into rare-variant heterozygotes and non-heterozygotes.RESULTS:
Risk for ALS was significantly associated with PRS and rare variants independently in a logistic regression model. Although ALS PRS predicted a small amount of ALS risk overall, the effect was most pronounced between ALS cases and controls that were not heterozygous for a rare variant in the ALS genes surveyed.CONCLUSION:
Both PRS and rare variants in ALS genes impact risk for ALS. PRS for ALS is most informative when rare variants are not observed in ALS genes.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Esclerosis Amiotrófica Lateral
Tipo de estudio:
Prognostic_studies
Límite:
Humans
País/Región como asunto:
America do norte
Idioma:
En
Revista:
Genet Med
Asunto de la revista:
GENETICA MEDICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Canadá