18654
2016
eng
3163-3169
139
article
1
2019-08-28
--
--
Genome-wide association study in essential tremor identifies three new loci
We conducted a genome-wide association study of essential tremor, a common movement disorder characterized mainly by a postural and kinetic tremor of the upper extremities. Twin and family history studies show a high heritability for essential tremor. The molecular genetic determinants of essential tremor are unknown. We included 2807 patients and 6441 controls of European descent in our two-stage genome-wide association study. The 59 most significantly disease-associated markers of the discovery stage were genotyped in the replication stage. After Bonferroni correction two markers, one (rs10937625) located in the serine/threonine kinase STK32B and one (rs17590046) in the transcriptional coactivator PPARGC1A were associated with essential tremor. Three markers (rs12764057, rs10822974, rs7903491) in the cell-adhesion molecule CTNNA3 were significant in the combined analysis of both stages. The expression of STK32B was increased in the cerebellar cortex of patients and expression quantitative trait loci database mining showed association between the protective minor allele of rs10937625 and reduced expression in cerebellar cortex. We found no expression differences related to disease status or marker genotype for the other two genes. Replication of two lead single nucleotide polymorphisms of previous small genome-wide association studies (rs3794087 in SLC1A2, rs9652490 in LINGO1) did not confirm the association with essential tremor.
Brain
10.1093/brain/aww242
urn:nbn:de:bvb:20-opus-186541
Brain (2016) 139:3163-3169. https://doi.org/10.1093/brain/aww242
false
true
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Stefanie H. Müller
Simon L. Girard
Franziska Hopfner
Nancy D. Merner
Cynthia V. Bourassa
Delia Lorenz
Lorraine N. Clark
Lukas Tittmann
Alexandra I. Soto-Ortolaza
Stephan Klebe
Mark Hallett
Susanne A. Schneider
Colin A. Hodgkinson
Wolfgang Lieb
Zbigniew K. Wszolek
Manuela Pendziwiat
Oswaldo Lorenzo-Betancor
Werner Poewe
Sara Ortega-Cubero
Klaus Seppi
Alex Rajput
Anna Hussl
Ali H. Rajput
Daniela Berg
Patrick A. Dion
Isabel Wurster
Joshua M. Shulman
Karin Srulijes
Dietrich Haubenberger
Pau Pastor
Carles Vilariño-Güell
Ronald B. Postuma
Geneviève Bernard
Karl-Heinz Ladwig
Nicolas Dupré
Joseph Jankovic
Konstantin Strauch
Michel Panisset
Juliane Winkelmann
Claudia M. Testa
Eva Reischl
Kirsten E. Zeuner
Owen A. Ross
Thomas Arzberger
Sylvain Chouinard
Günther Deuschl
Elan D. Louis
Gregor Kuhlenbäumer
Guy A. Rouleau
eng
uncontrolled
quality-control
eng
uncontrolled
disease
eng
uncontrolled
tool
eng
uncontrolled
movement disorders
eng
uncontrolled
genome-wide association study
eng
uncontrolled
tremor
eng
uncontrolled
genetics
eng
uncontrolled
essential tremor
Medizin und Gesundheit
open_access
Kinderklinik und Poliklinik
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/18654/Mueller_BRAIN_2016.pdf
13093
2013
eng
e65636
6
8
article
1
2016-03-31
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--
Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report
Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study.
Materials and Methods: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (\(\kappa\))] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling.
Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (\(\kappa\) = 0.66 and \(\kappa\) = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (\(ICC_1 = 0.71\) and \(ICC_2 = 0.75\), respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders).
Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.
PLoS ONE
10.1371/journal.pone.0065636
urn:nbn:de:bvb:20-opus-130938
PLoS ONE 8(6): e65636. doi:10.1371/journal.pone.0065636
Mirko Manchia
Mazda Adli
Nirmala Akula
Raffaella Arda
Jean-Michel Aubry
Lena Backlund
Claudio E. M. Banzato
Bernhard T. Baune
Frank Bellivier
Susanne Bengesser
Joanna M. Biernacka
Clara Brichant-Petitjean
Elise Bui
Cynthia V. Calkin
Andrew Tai Ann Cheng
Caterina Chillotti
Sven Cichon
Scott Clark
Piotr M. Czerski
Clarissa Dantas
Maria Del Zompo
J. Raymond DePaulo
Sevilla D. Detera-Wadleigh
Bruno Etain
Peter Falkai
Louise Frisén
Mark A. Frye
Jan Fullerton
Sébastien Gard
Julie Garnham
Fernando S. Goes
Paul Grof
Oliver Gruber
Ryota Hashimoto
Joanna Hauser
Urs Heilbronner
Rebecca Hoban
Liping Hou
Stéphane Jamain
Jean-Pierre Kahn
Layla Kassem
Tadafumi Kato
John R. Kelsoe
Sarah Kittel-Schneider
Sebastian Kliwicki
Po-Hsiu Kuo
Ichiro Kusumi
Gonzalo Laje
Catharina Lavebratt
Marion Leboyer
Susan G. Leckband
Carlos A. López Jaramillo
Mario Maj
Alain Malafosse
Lina Martinsson
Takuya Masui
Philip B. Mitchell
Frank Mondimore
Palmiero Monteleone
Audrey Nallet
Maria Neuner
Tomás Novák
Claire O'Donovan
Urban Ösby
Norio Ozaki
Roy H. Perlis
Andrea Pfennig
James B. Potash
Daniela Reich-Erkelenz
Andreas Reif
Eva Reininghaus
Sara Richardson
Guy A. Rouleau
Janusz K. Rybakowski
Martin Schalling
Peter R. Schofield
Oliver K. Schubert
Barbara Schweizer
Florian Seemüller
Maria Grigoroiu-Serbanescu
Giovanni Severino
Lisa R. Seymour
Claire Slaney
Jordan W. Smoller
Alessio Squassina
Thomas Stamm
Jo Steele
Pavla Stopkova
Sarah K. Tighe
Alfonso Tortorella
Gustavo Turecki
Naomi R. Wray
Adam Wright
Peter P. Zandi
David Zilles
Michael Bauer
Marcella Rietschel
Francis J. McMahon
Thomas G. Schulze
Martin Alda
eng
uncontrolled
age
eng
uncontrolled
observer agreement
eng
uncontrolled
prophylactic lithium
eng
uncontrolled
mapping susceptibility genes
eng
uncontrolled
mood disorders
eng
uncontrolled
onset
eng
uncontrolled
association
eng
uncontrolled
reliability
eng
uncontrolled
morality
eng
uncontrolled
illness
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13093/079_Manchia_Plos_One.pdf
12737
2013
eng
e1003864
10
9
article
1
2016-02-18
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Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture
The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
PLoS Genetics
10.1371/journal.pgen.1003864
1553-7390
urn:nbn:de:bvb:20-opus-127377
PLoS Genetics 9(10): e1003864. doi:10.1371/journal.pgen.1003864
Lea K. Davis
Dongmei Yu
Clare L. Keenan
Eric R. Gamazon
Anuar I. Konkashbaev
Eske M. Derks
Benjamin M. Neale
Jian Yang
S. Hong Lee
Patrick Evans
Cathy L. Barr
Laura Bellodi
Fortu Benarroch
Gabriel Bedoya Berrio
Oscar J. Bienvenu
Michael H. Bloch
Rianne M. Blom
Ruth D. Bruun
Cathy L. Budman
Beatriz Camarena
Desmond Campbell
Carolina Cappi
Julio C. Cardona Silgado
Danielle C. Cath
Maria C. Cavallini
Denise A. Chavira
Sylvian Chouinard
David V. Conti
Edwin H. Cook
Vladimir Coric
Bernadette A. Cullen
Dieter Deforce
Richard Delorme
Yves Dion
Christopher K. Edlund
Karin Egberts
Peter Falkai
Thomas V. Fernandez
Patience J. Gallagher
Helena Garrido
Daniel Geller
Simon L. Girard
Hans J. Grabe
Marco A. Grados
Benjamin D. Greenberg
Varda Gross-Tsur
Stephen Haddad
Gary A. Heiman
Sian M. J. Hemmings
Ana G. Hounie
Cornelia Illmann
Joseph Jankovic
Micheal A. Jenike
James L. Kennedy
Robert A. King
Barbara Kremeyer
Roger Kurlan
Nuria Lanzagorta
Marion Leboyer
James F. Leckman
Leonhard Lennertz
Chunyu Liu
Christine Lochner
Thomas L. Lowe
Fabio Macciardi
James T. McCracken
Lauren M. McGrath
Sandra C. Mesa Restrepo
Rainald Moessner
Jubel Morgan
Heike Muller
Dennis L. Murphy
Allan L. Naarden
William Cornejo Ochoa
Roel A. Ophoff
Lisa Osiecki
Andrew J. Pakstis
Michele T. Pato
Carlos N. Pato
John Piacentini
Christopher Pittenger
Yehunda Pollak
Scott L. Rauch
Tobias J. Renner
Victor I. Reus
Margaret A. Richter
Mark A. Riddle
Mary M. Robertson
Roxana Romero
Maria C. Rosàrio
David Rosenberg
Guy A. Rouleau
Stephan Ruhrmann
Andreas Ruiz-Linares
Aline S. Sampaio
Jack Samuels
Paul Sandor
Broke Sheppard
Harvey S. Singer
Jan H. Smit
Dan J. Stein
E. Strengman
Jay A. Tischfield
Ana V. Valencia Duarte
Homero Vallada
Flip Van Nieuwerburgh
Jeremy Veenstra-VanderWeele
Susanne Walitza
Ying Wang
Jens R. Wendland
Herman G. M. Westenberg
Yin Yao Shugart
Euripedes C. Miguel
William McMahon
Michael Wagner
Humberto Nicolini
Danielle Posthuma
Gregory L. Hanna
Peter Heutink
Damiaan Denys
Paul D. Arnold
Ben A. Oostra
Gerald Nestadt
Nelson B. Freimer
David L. Pauls
Naomi R. Wray
S. Evelyn Stewart
Carol A. Mathews
James A. Knowles
Nancy J. Cox
Jeremiah M. Scharf
eng
uncontrolled
TIC disorders
eng
uncontrolled
missing heritability
eng
uncontrolled
complex diseases
eng
uncontrolled
neuropsychiatric disorders
eng
uncontrolled
common SNPS
eng
uncontrolled
gilles
eng
uncontrolled
family
eng
uncontrolled
brain
eng
uncontrolled
expression
eng
uncontrolled
autism
Krankheiten
open_access
Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12737/058_Davis_Plos_Genetics.pdf