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@ARTICLE{Billingsley:255487,
author = {Billingsley, Kimberley J and Ding, Jinhui and Jerez, Pilar
Alvarez and Illarionova, Anastasia and Levine, Kristin and
Grenn, Francis P and Makarious, Mary B and Moore, Anni and
Vitale, Daniel and Reed, Xylena and Hernandez, Dena and
Torkamani, Ali and Ryten, Mina and Hardy, John and Chia,
Ruth and Scholz, Sonja W and Traynor, Bryan J and Dalgard,
Clifton L and Ehrlich, Debra J and Tanaka, Toshiko and
Ferrucci, Luigi and Beach, Thomas G and Serrano, Geidy E and
Quinn, John P and Bubb, Vivien J and Collins, Ryan L and
Zhao, Xuefang and Walker, Mark and Pierce-Hoffman, Emma and
Brand, Harrison and Talkowski, Michael E and Casey, Bradford
and Cookson, Mark R and Markham, Androo and Nalls, Mike A
and Mahmoud, Medhat and Sedlazeck, Fritz J and Blauwendraat,
Cornelis and Gibbs, J Raphael and Singleton, Andrew B},
collaboration = {Consortium, UK Brain Expression},
title = {{G}enome-{W}ide {A}nalysis of {S}tructural {V}ariants in
{P}arkinson {D}isease.},
journal = {Annals of neurology},
volume = {93},
number = {5},
issn = {0364-5134},
address = {Hoboken, NJ},
publisher = {Wiley-Blackwell},
reportid = {DZNE-2023-00288},
pages = {1012-1022},
year = {2023},
note = {CC BY-NC},
abstract = {Identification of genetic risk factors for Parkinson
disease (PD) has to date been primarily limited to the study
of single nucleotide variants, which only represent a small
fraction of the genetic variation in the human genome.
Consequently, causal variants for most PD risk are not
known. Here we focused on structural variants (SVs), which
represent a major source of genetic variation in the human
genome. We aimed to discover SVs associated with PD risk by
performing the first large-scale characterization of SVs in
PD.We leveraged a recently developed computational pipeline
to detect and genotype SVs from 7,772 Illumina short-read
whole genome sequencing samples. Using this set of SV
variants, we performed a genome-wide association study using
2,585 cases and 2,779 controls and identified SVs associated
with PD risk. Furthermore, to validate the presence of these
variants, we generated a subset of matched whole-genome
long-read sequencing data.We genotyped and tested 3,154
common SVs, representing over 412 million nucleotides of
previously uncatalogued genetic variation. Using long-read
sequencing data, we validated the presence of three novel
deletion SVs that are associated with risk of PD from our
initial association analysis, including a 2 kb intronic
deletion within the gene LRRN4.We identified three SVs
associated with genetic risk of PD. This study represents
the most comprehensive assessment of the contribution of SVs
to the genetic risk of PD to date. ANN NEUROL
2023;93:1012-1022.},
keywords = {Humans / Genome-Wide Association Study / Parkinson Disease:
genetics / Genome, Human / Whole Genome Sequencing /
Genotype},
cin = {Core ICRU},
ddc = {610},
cid = {I:(DE-2719)1240005},
pnm = {899 - ohne Topic (POF4-899) / 353 - Clinical and Health
Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-899 / G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC10192042},
pubmed = {pmid:36695634},
doi = {10.1002/ana.26608},
url = {https://pub.dzne.de/record/255487},
}