A local ancestry-based assessment of common variants to finetune risk profiles of Parkinson’s disease (PD)
Session Number
Project ID: MEDH 25
Advisor(s)
Dr. Steven Lubbe; Northwestern University, Feinberg School of Medicine
Dr. Bernabe Bustos; Northwestern University, Feinberg School of Medicine
Discipline
Medical and Health Sciences
Start Date
19-4-2023 11:55 AM
End Date
19-4-2023 12:20 PM
Abstract
Parkinson’s disease (PD) is a severe neurodegenerative disease resulting from complex interactions between genetic and environmental factors. Past studies have estimated the genetic heritability of PD at around 24-60%, but they have examined samples of European ancestry as genetically homogenous.
Historical trends, however, find that Northern and Southern European tribes interbred between 440 and 1,080 CE, leading to 2-100 different genetic ancestors in Europe today. We examined such local variation, specifically at the chromosomal level, which PCAs overlook. With a merged, pruned, and harmonized dataset from the 1000 Genomes Project and the POPRES: Population Reference Sample, this study conducted ADMIXTURE, which found most significant individual ancestries at K=14 (with p < 0.05 and Fsp > 0.15 as significant thresholds). Logistic regression was then performed for the first 10 PCs with LAMP-LD, building a hidden-Markov model with a window of 100 variants.
We found that each individual obtains 34% of ancestry from North Europe and 66% from the South. A Manhattan plot found that variants were significant on chromosomes 4, 6, 15, and 17 for North Europe and 15 and 16 for South Europe.
A local ancestry-based assessment of common variants to finetune risk profiles of Parkinson’s disease (PD)
Parkinson’s disease (PD) is a severe neurodegenerative disease resulting from complex interactions between genetic and environmental factors. Past studies have estimated the genetic heritability of PD at around 24-60%, but they have examined samples of European ancestry as genetically homogenous.
Historical trends, however, find that Northern and Southern European tribes interbred between 440 and 1,080 CE, leading to 2-100 different genetic ancestors in Europe today. We examined such local variation, specifically at the chromosomal level, which PCAs overlook. With a merged, pruned, and harmonized dataset from the 1000 Genomes Project and the POPRES: Population Reference Sample, this study conducted ADMIXTURE, which found most significant individual ancestries at K=14 (with p < 0.05 and Fsp > 0.15 as significant thresholds). Logistic regression was then performed for the first 10 PCs with LAMP-LD, building a hidden-Markov model with a window of 100 variants.
We found that each individual obtains 34% of ancestry from North Europe and 66% from the South. A Manhattan plot found that variants were significant on chromosomes 4, 6, 15, and 17 for North Europe and 15 and 16 for South Europe.