RESUMO
We collected and analyzed genomic sequencing data from individuals with clinician-diagnosed early-onset or atypical dementia. Thirty-two patients were previously described, with 68 newly described in this report. Of those 68, 62 patients self-reported white, non-Hispanic ethnicity and 6 reported as African-American, non-Hispanic. Fifty-three percent of patients had a returnable variant. Five patients harbored a pathogenic variant as defined by the American College of Medical Genetics criteria for pathogenicity. A polygenic risk score (PRS) was calculated for Alzheimer's patients in the total cohort and compared to the scores of a late-onset Alzheimer's cohort and a control set. Patients with early-onset Alzheimer's had higher non-APOE PRSs than patients with late-onset Alzheimer's, supporting the conclusion that both rare and common genetic variation associate with early-onset neurodegenerative disease risk.
Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Humanos , Doença de Alzheimer/genética , Apolipoproteínas E/genética , Fatores de RiscoRESUMO
We collected and analyzed genomic sequencing data from individuals with clinician- diagnosed early-onset or atypical dementia. Thirty-two patients were previously described, with sixty-eight newly described in this report. Of those sixty-eight, sixty-two patients reported Caucasian, non-Hispanic ethnicity and six reported as African American, non-Hispanic. Fifty-three percent of patients had a returnable variant. Five patients harbored a pathogenic variant as defined by the American College of Medical Genetics criteria for pathogenicity. A polygenic risk score was calculated for Alzheimer's patients in the total cohort and compared to the scores of a late-onset Alzheimer's cohort and a control set. Patients with early-onset Alzheimer's had higher non- APOE polygenic risk scores than patients with late onset Alzheimer's, supporting the conclusion that both rare and common genetic variation associate with early-onset neurodegenerative disease risk.