% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Lai:162738,
author = {Lai, Dongbing and Alipanahi, Babak and Fontanillas, Pierre
and Schwantes-An, Tae-Hwi and Aasly, Jan and Alcalay, Roy N
and Beecham, Gary W and Berg, Daniela and Bressman, Susan
and Brice, Alexis and Brockmann, Kathrin and Clark, Lorraine
and Cookson, Mark and Das, Sayantan and Van Deerlin,
Vivianna and Follett, Jordan and Farrer, Matthew J and
Trinh, Joanne and Gasser, Thomas and Goldwurm, Stefano and
Gustavsson, Emil and Klein, Christine and Lang, Anthony E
and Langston, J William and Latourelle, Jeanne and Lynch,
Timothy and Marder, Karen and Marras, Connie and Martin,
Eden R and McLean, Cory Y and Mejia-Santana, Helen and
Molho, Eric and Myers, Richard H and Nuytemans, Karen and
Ozelius, Laurie and Payami, Haydeh and Raymond, Deborah and
Rogaeva, Ekaterina and Rogers, Michael P and Ross, Owen A
and Samii, Ali and Saunders-Pullman, Rachel and Schüle,
Birgitt and Schulte, Claudia and Scott, William K and
Tanner, Caroline and Tolosa, Eduardo and Tomkins, James E
and Vilas, Dolores and Trojanowski, John Q and Uitti, Ryan
and Vance, Jeffery M and Visanji, Naomi P and Wszolek,
Zbigniew K and Zabetian, Cyrus P and Mirelman, Anat and
Giladi, Nir and Orr Urtreger, Avi and Cannon, Paul and
Fiske, Brian and Foroud, Tatiana},
collaboration = {Team, 23andMe Research},
title = {{G}enomewide {A}ssociation {S}tudies of {LRRK}2 {M}odifiers
of {P}arkinson's {D}isease.},
journal = {Annals of neurology},
volume = {90},
number = {1},
issn = {1531-8249},
address = {Hoboken, NJ},
publisher = {Wiley-Blackwell},
reportid = {DZNE-2021-01395},
pages = {76 - 88},
year = {2021},
abstract = {The aim of this study was to search for genes/variants that
modify the effect of LRRK2 mutations in terms of penetrance
and age-at-onset of Parkinson's disease.We performed the
first genomewide association study of penetrance and
age-at-onset of Parkinson's disease in LRRK2 mutation
carriers (776 cases and 1,103 non-cases at their last
evaluation). Cox proportional hazard models and linear mixed
models were used to identify modifiers of penetrance and
age-at-onset of LRRK2 mutations, respectively. We also
investigated whether a polygenic risk score derived from a
published genomewide association study of Parkinson's
disease was able to explain variability in penetrance and
age-at-onset in LRRK2 mutation carriers.A variant located in
the intronic region of CORO1C on chromosome 12 (rs77395454;
p value = 2.5E-08, beta = 1.27, SE = 0.23, risk
allele: C) met genomewide significance for the penetrance
model. Co-immunoprecipitation analyses of LRRK2 and CORO1C
supported an interaction between these 2 proteins. A region
on chromosome 3, within a previously reported linkage peak
for Parkinson's disease susceptibility, showed suggestive
associations in both models (penetrance top variant: p
value = 1.1E-07; age-at-onset top variant: p
value = 9.3E-07). A polygenic risk score derived from
publicly available Parkinson's disease summary statistics
was a significant predictor of penetrance, but not of
age-at-onset.This study suggests that variants within or
near CORO1C may modify the penetrance of LRRK2 mutations. In
addition, common Parkinson's disease associated variants
collectively increase the penetrance of LRRK2 mutations. ANN
NEUROL 2021;90:82-94.},
keywords = {Aged / Female / Genetic Predisposition to Disease /
Genome-Wide Association Study / Genotype / Humans /
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2:
genetics / Male / Middle Aged / Mutation / Parkinson
Disease: genetics / Penetrance / Leucine-Rich Repeat
Serine-Threonine Protein Kinase-2 (NLM Chemicals)},
cin = {AG Gasser / AG Berg},
ddc = {610},
cid = {I:(DE-2719)1210000 / I:(DE-2719)5000055},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33938021},
pmc = {pmc:PMC8252519},
doi = {10.1002/ana.26094},
url = {https://pub.dzne.de/record/162738},
}