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50bp deletion in the promoter for superoxide dismutase 1 (SOD1) reduces SOD1 expression in vitro and may correlate with increased age of onset of sporadic amyotrophic lateral sclerosis.

https://arctichealth.org/en/permalink/ahliterature156293
Source
Amyotroph Lateral Scler. 2008 Aug;9(4):229-37
Publication Type
Article
Date
Aug-2008
Author
Wendy J Broom
Matthew Greenway
Ghazaleh Sadri-Vakili
Carsten Russ
Kristen E Auwarter
Kelly E Glajch
Nicolas Dupre
Robert J Swingler
Shaun Purcell
Caroline Hayward
Peter C Sapp
Diane McKenna-Yasek
Paul N Valdmanis
Jean-Pierre Bouchard
Vincent Meininger
Betsy A Hosler
Jonathan D Glass
Meraida Polack
Guy A Rouleau
Jang-Ho J Cha
Orla Hardiman
Robert H Brown
Author Affiliation
Day Neuromuscular Research Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA. wendy.broom@gmail.com
Source
Amyotroph Lateral Scler. 2008 Aug;9(4):229-37
Date
Aug-2008
Language
English
Publication Type
Article
Keywords
Age of Onset
Amyotrophic Lateral Sclerosis - enzymology - epidemiology - genetics
Base Sequence
DNA Mutational Analysis
Female
Gene Expression
Genetic Predisposition to Disease
Genotype
Homozygote
Humans
Ireland - epidemiology
Male
Middle Aged
Phenotype
Polymorphism, Genetic
Promoter Regions, Genetic
Quebec - epidemiology
Risk factors
Scotland - epidemiology
Sequence Deletion
Sp1 Transcription Factor - metabolism
Superoxide Dismutase - genetics - metabolism
United States - epidemiology
Abstract
The objective was to test the hypothesis that a described association between homozygosity for a 50bp deletion in the SOD1 promoter 1684bp upstream of the SOD1 ATG and an increased age of onset in SALS can be replicated in additional SALS and control sample sets from other populations. Our second objective was to examine whether this deletion attenuates expression of the SOD1 gene. Genomic DNA from more than 1200 SALS cases from Ireland, Scotland, Quebec and the USA was genotyped for the 50bp SOD1 promoter deletion. Reporter gene expression analysis, electrophoretic mobility shift assays and chromatin immunoprecipitation studies were utilized to examine the functional effects of the deletion. The genetic association for homozygosity for the promoter deletion with an increased age of symptom onset was confirmed overall in this further study (p=0.032), although it was only statistically significant in the Irish subset, and remained highly significant in the combined set of all cohorts (p=0.001). Functional studies demonstrated that this polymorphism reduces the activity of the SOD1 promoter by approximately 50%. In addition we revealed that the transcription factor SP1 binds within the 50bp deletion region in vitro and in vivo. Our findings suggest the hypothesis that this deletion reduces expression of the SOD1 gene and that levels of the SOD1 protein may modify the phenotype of SALS within selected populations.
PubMed ID
18608091 View in PubMed
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Changing environmental influences on substance use across development.

https://arctichealth.org/en/permalink/ahliterature163053
Source
Twin Res Hum Genet. 2007 Apr;10(2):315-26
Publication Type
Article
Date
Apr-2007
Author
Danielle M Dick
Jason L Pagan
Richard Viken
Shaun Purcell
Jaakko Kaprio
Lea Pulkkinen
Richard J Rose
Author Affiliation
Washington University, Department of Psychiatry, St Louis, MO 63110, USA. dickd@wustl.edu
Source
Twin Res Hum Genet. 2007 Apr;10(2):315-26
Date
Apr-2007
Language
English
Publication Type
Article
Keywords
Adolescent
Adolescent Behavior
Adolescent Psychology
Alcohol Drinking - genetics - psychology
Child
Cohort Studies
Environment
Female
Finland
Genetic Predisposition to Disease
Humans
Male
Parenting
Peer Group
Phenotype
Questionnaires
Smoking - genetics - psychology
Twins, Dizygotic - genetics - psychology
Twins, Monozygotic - genetics - psychology
Abstract
In contrast to many phenotypes that have been studied using twin designs, substance use shows considerable evidence of environmental influence. Accordingly, specifying the relevant environments and understanding the nature of their effects is an important research priority. Twin studies also have demonstrated that the importance of genetic and environmental influences varies across development for a variety of behavioral outcomes, including substance use. Here, we report analyses exploring moderating effects associated with parenting and peer characteristics on adolescent smoking and drinking, measured at ages 14 and 17. We find significant evidence of moderating effects associated with two dimensions of parenting (parental monitoring and time spent in activities with parents) on adolescent smoking, measured at two time points across development, but no moderating effects on adolescent drinking. Genetic influences on smoking increased, and common environmental effects decreased, as adolescents reported less parental monitoring and spending more time with their parents. Conversely, we find evidence that adolescent drinking is more strongly influenced by peer characteristics. The importance of genetic predispositions was increased among adolescents who reported more friends who used alcohol. These analyses illustrate the importance of incorporating measured aspects of the environment into genetically informative twin models to begin to understand how specific environments are related to various outcomes. Furthermore, they illustrate the importance of using a developmental perspective to understand how specific influences may vary across different ages, and across different phenotypes.
Notes
Cites: Pediatrics. 1994 Jun;93(6 Pt 2):1060-48197008
Cites: J Abnorm Psychol. 1993 Feb;102(1):3-198436697
Cites: Hum Biol. 1995 Oct;67(5):739-538543288
Cites: J Stud Alcohol Suppl. 1999 Mar;13:63-7410225489
Cites: Behav Genet. 2005 Jul;35(4):491-815971029
Cites: Genes Brain Behav. 2005 Nov;4(8):466-8116268991
Cites: Child Dev. 2005 Nov-Dec;76(6):1217-3316274436
Cites: Hum Genet. 2006 Apr;119(3):312-2116463022
Cites: Twin Res. 1999 Dec;2(4):274-8510723806
Cites: Dev Psychol. 2000 May;36(3):366-8010830980
Cites: Child Dev. 2000 Jul-Aug;71(4):1072-8511016567
Cites: Alcohol Clin Exp Res. 2001 May;25(5):637-4311371711
Cites: Alcohol Clin Exp Res. 2001 Nov;25(11):1594-60411707634
Cites: J Abnorm Psychol. 2001 Nov;110(4):625-3211727951
Cites: J Neurobiol. 2003 Jan;54(1):4-4512486697
Cites: Twin Res. 2002 Dec;5(6):554-7112573187
Cites: Twin Res. 2002 Oct;5(5):366-7112537860
Cites: Child Dev. 2003 Jan-Feb;74(1):109-2612625439
Cites: Drug Alcohol Depend. 2003 Apr 1;69(3):253-6212633911
Cites: Int J Eat Disord. 2003 Apr;33(3):287-9212655625
Cites: Psychol Sci. 2003 May;14(3):273-712741753
Cites: J Adolesc Health. 2003 Aug;33(2):60-7012890596
Cites: J Adolesc Health. 2003 Aug;33(2):108-1812890602
Cites: J Child Psychol Psychiatry. 2003 Nov;44(8):1130-4414626455
Cites: Psychol Sci. 2003 Nov;14(6):623-814629696
Cites: Am J Drug Alcohol Abuse. 1988;14(4):487-983232681
Cites: Behav Genet. 1991 May;21(3):257-691863259
Cites: Behav Genet. 1994 May;24(3):239-587945154
PubMed ID
17564520 View in PubMed
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Genome-wide association analysis identifies 13 new risk loci for schizophrenia.

https://arctichealth.org/en/permalink/ahliterature107798
Source
Nat Genet. 2013 Oct;45(10):1150-9
Publication Type
Article
Date
Oct-2013
Author
Stephan Ripke
Colm O'Dushlaine
Kimberly Chambert
Jennifer L Moran
Anna K Kähler
Susanne Akterin
Sarah E Bergen
Ann L Collins
James J Crowley
Menachem Fromer
Yunjung Kim
Sang Hong Lee
Patrik K E Magnusson
Nick Sanchez
Eli A Stahl
Stephanie Williams
Naomi R Wray
Kai Xia
Francesco Bettella
Anders D Borglum
Brendan K Bulik-Sullivan
Paul Cormican
Nick Craddock
Christiaan de Leeuw
Naser Durmishi
Michael Gill
Vera Golimbet
Marian L Hamshere
Peter Holmans
David M Hougaard
Kenneth S Kendler
Kuang Lin
Derek W Morris
Ole Mors
Preben B Mortensen
Benjamin M Neale
Francis A O'Neill
Michael J Owen
Milica Pejovic Milovancevic
Danielle Posthuma
John Powell
Alexander L Richards
Brien P Riley
Douglas Ruderfer
Dan Rujescu
Engilbert Sigurdsson
Teimuraz Silagadze
August B Smit
Hreinn Stefansson
Stacy Steinberg
Jaana Suvisaari
Sarah Tosato
Matthijs Verhage
James T Walters
Douglas F Levinson
Pablo V Gejman
Claudine Laurent
Bryan J Mowry
Michael C O'Donovan
Ann E Pulver
Sibylle G Schwab
Dieter B Wildenauer
Frank Dudbridge
Jianxin Shi
Margot Albus
Madeline Alexander
Dominique Campion
David Cohen
Dimitris Dikeos
Jubao Duan
Peter Eichhammer
Stephanie Godard
Mark Hansen
F Bernard Lerer
Kung-Yee Liang
Wolfgang Maier
Jacques Mallet
Deborah A Nertney
Gerald Nestadt
Nadine Norton
George N Papadimitriou
Robert Ribble
Alan R Sanders
Jeremy M Silverman
Dermot Walsh
Nigel M Williams
Brandon Wormley
Maria J Arranz
Steven Bakker
Stephan Bender
Elvira Bramon
David Collier
Benedicto Crespo-Facorro
Jeremy Hall
Conrad Iyegbe
Assen Jablensky
Rene S Kahn
Luba Kalaydjieva
Stephen Lawrie
Cathryn M Lewis
Don H Linszen
Ignacio Mata
Andrew McIntosh
Robin M Murray
Roel A Ophoff
Jim Van Os
Muriel Walshe
Matthias Weisbrod
Durk Wiersma
Peter Donnelly
Ines Barroso
Jenefer M Blackwell
Matthew A Brown
Juan P Casas
Aiden P Corvin
Panos Deloukas
Audrey Duncanson
Janusz Jankowski
Hugh S Markus
Christopher G Mathew
Colin N A Palmer
Robert Plomin
Anna Rautanen
Stephen J Sawcer
Richard C Trembath
Ananth C Viswanathan
Nicholas W Wood
Chris C A Spencer
Gavin Band
Céline Bellenguez
Colin Freeman
Garrett Hellenthal
Eleni Giannoulatou
Matti Pirinen
Richard D Pearson
Amy Strange
Zhan Su
Damjan Vukcevic
Cordelia Langford
Sarah E Hunt
Sarah Edkins
Rhian Gwilliam
Hannah Blackburn
Suzannah J Bumpstead
Serge Dronov
Matthew Gillman
Emma Gray
Naomi Hammond
Alagurevathi Jayakumar
Owen T McCann
Jennifer Liddle
Simon C Potter
Radhi Ravindrarajah
Michelle Ricketts
Avazeh Tashakkori-Ghanbaria
Matthew J Waller
Paul Weston
Sara Widaa
Pamela Whittaker
Mark I McCarthy
Kari Stefansson
Edward Scolnick
Shaun Purcell
Steven A McCarroll
Pamela Sklar
Christina M Hultman
Patrick F Sullivan
Author Affiliation
1] Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA. [2] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [3].
Source
Nat Genet. 2013 Oct;45(10):1150-9
Date
Oct-2013
Language
English
Publication Type
Article
Keywords
Case-Control Studies
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Male
Polymorphism, Single Nucleotide
Schizophrenia - genetics
Sweden
Abstract
Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.
Notes
Cites: Schizophr Bull. 2006 Jan;32(1):195-716135560
Cites: Am J Epidemiol. 2006 Feb 1;163(3):197-20316339049
Cites: Epidemiology. 2006 May;17(3):252-416617271
Cites: Psychol Med. 2006 Oct;36(10):1417-2516863597
Cites: Biochim Biophys Acta. 2006 Nov;1763(11):1169-7417034879
Cites: Psychol Med. 2007 Aug;37(8):1109-1817493296
Cites: Am J Hum Genet. 2007 Sep;81(3):559-7517701901
Cites: Arch Gen Psychiatry. 2007 Oct;64(10):1123-3117909124
Cites: Learn Mem. 2008 Jan;15(1):1-518174367
Cites: Eur J Hum Genet. 2008 Apr;16(4):422-3418197188
Cites: Nature. 2008 Mar 27;452(7186):423-818344981
Cites: Genet Epidemiol. 2008 May;32(4):381-518348202
Cites: Nord J Psychiatry. 2008;62(5):342-518752109
Cites: Hum Mol Genet. 2008 Oct 15;17(R2):R122-818852200
Cites: Lancet. 2009 Jan 17;373(9659):234-919150704
Cites: Nat Genet. 2008 Sep;40(9):1056-818711365
Cites: Nat Rev Genet. 2009 Mar;10(3):184-9419223927
Cites: Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9362-719474294
Cites: Mol Psychiatry. 2009 Aug;14(8):774-8519349958
Cites: Nature. 2009 Aug 6;460(7256):744-719571808
Cites: Nature. 2009 Aug 6;460(7256):753-719571809
Cites: Nature. 2009 Aug 6;460(7256):748-5219571811
Cites: Schizophr Bull. 2010 Jan;36(1):14-2319996148
Cites: Br J Psychiatry. 2010 Feb;196(2):92-520118450
Cites: J Cell Biol. 2010 Apr 5;189(1):127-4120368621
Cites: Cell. 2004 Oct 1;119(1):19-3115454078
Cites: N Engl J Med. 1996 Jul 25;335(4):242-98657240
Cites: BMJ. 1999 Feb 13;318(7181):421-69974454
Cites: Cell. 2005 Jan 14;120(1):15-2015652477
Cites: PLoS Med. 2005 May;2(5):e14115916472
Cites: Int Clin Psychopharmacol. 2005 Sep;20(5):243-5116096514
Cites: J Neurosci. 2005 Oct 26;25(43):9883-9216251435
Cites: Hum Mol Genet. 2010 Sep 1;19(17):3482-820601676
Cites: Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):14950-720668236
Cites: PLoS Genet. 2010 Apr;6(4):e100088820369019
Cites: Proc Natl Acad Sci U S A. 2010 May 18;107(20):9287-9220442332
Cites: Nat Genet. 2010 Jun;42(6):508-1420453842
Cites: PLoS One. 2010;5(5):e1069320502693
Cites: Stem Cells. 2010 Jun;28(6):1060-7020506192
Cites: Nat Genet. 2010 Jul;42(7):570-520562874
Cites: Am J Psychiatry. 2010 Jul;167(7):741-420595425
Cites: Science. 2012 Sep 7;337(6099):1190-522955828
Cites: Mol Psychiatry. 2012 Oct;17(10):996-100621931320
Cites: Biol Psychiatry. 2012 Oct 15;72(8):620-822883433
Cites: Nat Genet. 2012 Oct;44(10):1084-922941192
Cites: Nat Genet. 2012 Dec;44(12):1365-923042115
Cites: Can J Cardiol. 2013 Jan;29(1):89-9923062665
Cites: Mol Psychiatry. 2013 Apr;18(4):497-51122472876
Cites: Mol Psychiatry. 2013 Jun;18(6):708-1222614287
Cites: Am J Hum Genet. 2007 Apr;80(4):588-60417357067
Cites: Nat Genet. 2011 Oct;43(10):977-8321926972
Cites: Nat Genet. 2011 Oct;43(10):969-7621926974
Cites: J Med Genet. 2011 Dec;48(12):810-822003227
Cites: Mol Psychiatry. 2012 Jan;17(1):2-321826059
Cites: Nat Methods. 2012 Feb;9(2):179-8122138821
Cites: Nature. 2012 Feb 16;482(7385):390-422307276
Cites: Nat Genet. 2012 Mar;44(3):247-5022344220
Cites: PLoS Genet. 2012;8(4):e100263922532805
Cites: Nat Genet. 2012 May;44(5):483-922446960
Cites: Bioinformatics. 2012 Jul 1;28(13):1797-922513993
Cites: Am J Hum Genet. 2012 Jul 13;91(1):38-5522726847
Cites: Nat Rev Genet. 2012 Aug;13(8):537-5122777127
Cites: Am J Hum Genet. 2012 Aug 10;91(2):303-1222863191
Cites: Eur J Hum Genet. 2012 Sep;20(9):1004-822433715
Cites: Mol Psychiatry. 2012 Sep;17(9):880-622688191
Cites: Am J Psychiatry. 2012 Sep;169(9):963-7322885689
Cites: Nature. 2012 Sep 6;489(7414):57-7422955616
Cites: Nature. 2012 Sep 6;489(7414):75-8222955617
Cites: Neuron. 2000 Jan;25(1):177-9010707982
Cites: N Engl J Med. 2001 Mar 15;344(11):808-1411248156
Cites: Biometrics. 1999 Dec;55(4):997-100411315092
Cites: Soc Psychiatry Psychiatr Epidemiol. 2002 Nov;37(11):527-3112395142
Cites: Am J Psychiatry. 2003 Dec;160(12):2216-2114638593
Cites: Arch Gen Psychiatry. 2003 Dec;60(12):1187-9214662550
Cites: Neurobiol Learn Mem. 2004 Mar;81(2):105-1414990230
Cites: Genetics. 2004 Feb;166(2):835-8115020472
Cites: Schizophr Bull. 2004;30(2):279-9315279046
Cites: Nature. 2010 Oct 14;467(7317):832-820881960
Cites: Nat Genet. 2010 Nov;42(11):937-4820935630
Cites: Am J Hum Genet. 2011 Jan 7;88(1):76-8221167468
Cites: Trends Genet. 2011 Feb;27(2):72-921122937
Cites: Nature. 2011 Feb 10;470(7333):187-9721307931
Cites: Brain Res. 2011 Mar 22;1380:42-7721129364
Cites: Am J Hum Genet. 2011 Mar 11;88(3):372-8121353194
Cites: Schizophr Bull. 2011 May;37(3):456-6321505112
Cites: Eur J Hum Genet. 2011 Jul;19(7):807-1221407268
Cites: Nat Genet. 2011 Sep;43(9):860-321743468
Cites: Genes Dev. 2011 Sep 15;25(18):1915-2721890647
Cites: Prog Biophys Mol Biol. 2006 Jan-Apr;90(1-3):38-6315979127
PubMed ID
23974872 View in PubMed
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A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk.

https://arctichealth.org/en/permalink/ahliterature285363
Source
Diabetes. 2017 Jul;66(7):2019-2032
Publication Type
Article
Date
Jul-2017
Author
Alisa Manning
Heather M Highland
Jessica Gasser
Xueling Sim
Taru Tukiainen
Pierre Fontanillas
Niels Grarup
Manuel A Rivas
Anubha Mahajan
Adam E Locke
Pablo Cingolani
Tune H Pers
Ana Viñuela
Andrew A Brown
Ying Wu
Jason Flannick
Christian Fuchsberger
Eric R Gamazon
Kyle J Gaulton
Hae Kyung Im
Tanya M Teslovich
Thomas W Blackwell
Jette Bork-Jensen
Noël P Burtt
Yuhui Chen
Todd Green
Christopher Hartl
Hyun Min Kang
Ashish Kumar
Claes Ladenvall
Clement Ma
Loukas Moutsianas
Richard D Pearson
John R B Perry
N William Rayner
Neil R Robertson
Laura J Scott
Martijn van de Bunt
Johan G Eriksson
Antti Jula
Seppo Koskinen
Terho Lehtimäki
Aarno Palotie
Olli T Raitakari
Suzanne B R Jacobs
Jennifer Wessel
Audrey Y Chu
Robert A Scott
Mark O Goodarzi
Christine Blancher
Gemma Buck
David Buck
Peter S Chines
Stacey Gabriel
Anette P Gjesing
Christopher J Groves
Mette Hollensted
Jeroen R Huyghe
Anne U Jackson
Goo Jun
Johanne Marie Justesen
Massimo Mangino
Jacquelyn Murphy
Matt Neville
Robert Onofrio
Kerrin S Small
Heather M Stringham
Joseph Trakalo
Eric Banks
Jason Carey
Mauricio O Carneiro
Mark DePristo
Yossi Farjoun
Timothy Fennell
Jacqueline I Goldstein
George Grant
Martin Hrabé de Angelis
Jared Maguire
Benjamin M Neale
Ryan Poplin
Shaun Purcell
Thomas Schwarzmayr
Khalid Shakir
Joshua D Smith
Tim M Strom
Thomas Wieland
Jaana Lindstrom
Ivan Brandslund
Cramer Christensen
Gabriela L Surdulescu
Timo A Lakka
Alex S F Doney
Peter Nilsson
Nicholas J Wareham
Claudia Langenberg
Tibor V Varga
Paul W Franks
Olov Rolandsson
Anders H Rosengren
Vidya S Farook
Farook Thameem
Sobha Puppala
Satish Kumar
Donna M Lehman
Christopher P Jenkinson
Joanne E Curran
Daniel Esten Hale
Sharon P Fowler
Rector Arya
Ralph A DeFronzo
Hanna E Abboud
Ann-Christine Syvänen
Pamela J Hicks
Nicholette D Palmer
Maggie C Y Ng
Donald W Bowden
Barry I Freedman
Tõnu Esko
Reedik Mägi
Lili Milani
Evelin Mihailov
Andres Metspalu
Narisu Narisu
Leena Kinnunen
Lori L Bonnycastle
Amy Swift
Dorota Pasko
Andrew R Wood
João Fadista
Toni I Pollin
Nir Barzilai
Gil Atzmon
Benjamin Glaser
Barbara Thorand
Konstantin Strauch
Annette Peters
Michael Roden
Martina Müller-Nurasyid
Liming Liang
Jennifer Kriebel
Thomas Illig
Harald Grallert
Christian Gieger
Christa Meisinger
Lars Lannfelt
Solomon K Musani
Michael Griswold
Herman A Taylor
Gregory Wilson
Adolfo Correa
Heikki Oksa
William R Scott
Uzma Afzal
Sian-Tsung Tan
Marie Loh
John C Chambers
Jobanpreet Sehmi
Jaspal Singh Kooner
Benjamin Lehne
Yoon Shin Cho
Jong-Young Lee
Bok-Ghee Han
Annemari Käräjämäki
Qibin Qi
Lu Qi
Jinyan Huang
Frank B Hu
Olle Melander
Marju Orho-Melander
Jennifer E Below
David Aguilar
Tien Yin Wong
Jianjun Liu
Chiea-Chuen Khor
Kee Seng Chia
Wei Yen Lim
Ching-Yu Cheng
Edmund Chan
E Shyong Tai
Tin Aung
Allan Linneberg
Bo Isomaa
Thomas Meitinger
Tiinamaija Tuomi
Liisa Hakaste
Jasmina Kravic
Marit E Jørgensen
Torsten Lauritzen
Panos Deloukas
Kathleen E Stirrups
Katharine R Owen
Andrew J Farmer
Timothy M Frayling
Stephen P O'Rahilly
Mark Walker
Jonathan C Levy
Dylan Hodgkiss
Andrew T Hattersley
Teemu Kuulasmaa
Alena Stancáková
Inês Barroso
Dwaipayan Bharadwaj
Juliana Chan
Giriraj R Chandak
Mark J Daly
Peter J Donnelly
Shah B Ebrahim
Paul Elliott
Tasha Fingerlin
Philippe Froguel
Cheng Hu
Weiping Jia
Ronald C W Ma
Gilean McVean
Taesung Park
Dorairaj Prabhakaran
Manjinder Sandhu
James Scott
Rob Sladek
Nikhil Tandon
Yik Ying Teo
Eleftheria Zeggini
Richard M Watanabe
Heikki A Koistinen
Y Antero Kesaniemi
Matti Uusitupa
Timothy D Spector
Veikko Salomaa
Rainer Rauramaa
Colin N A Palmer
Inga Prokopenko
Andrew D Morris
Richard N Bergman
Francis S Collins
Lars Lind
Erik Ingelsson
Jaakko Tuomilehto
Fredrik Karpe
Leif Groop
Torben Jørgensen
Torben Hansen
Oluf Pedersen
Johanna Kuusisto
Gonçalo Abecasis
Graeme I Bell
John Blangero
Nancy J Cox
Ravindranath Duggirala
Mark Seielstad
James G Wilson
Josee Dupuis
Samuli Ripatti
Craig L Hanis
Jose C Florez
Karen L Mohlke
James B Meigs
Markku Laakso
Andrew P Morris
Michael Boehnke
David Altshuler
Mark I McCarthy
Anna L Gloyn
Cecilia M Lindgren
Source
Diabetes. 2017 Jul;66(7):2019-2032
Date
Jul-2017
Language
English
Publication Type
Article
Keywords
African Americans - genetics
Alleles
Asian Continental Ancestry Group - genetics
Case-Control Studies
Diabetes Mellitus, Type 2 - genetics - metabolism
European Continental Ancestry Group - genetics
Fasting - metabolism
Finland
Gene Frequency
Genetic Predisposition to Disease
Genotype
Hispanic Americans - genetics
Humans
Insulin - metabolism
Insulin Resistance - genetics
Odds Ratio
Proto-Oncogene Proteins c-akt - genetics
Abstract
To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
Notes
Cites: J Clin Invest. 2009 Feb;119(2):315-2219164855
Cites: Nature. 2014 Feb 6;506(7486):97-10124390345
Cites: Int J Epidemiol. 2008 Dec;37(6):1220-618263651
Cites: Am J Hum Genet. 2017 Mar 2;100(3):428-44328257690
Cites: Nucleic Acids Res. 2014 Jan;42(Database issue):D764-7024270787
Cites: Diabetes. 2007 Mar;56(3):714-917327441
Cites: PLoS Genet. 2014 Jul 31;10(7):e100449425078778
Cites: Cell Metab. 2006 Jul;4(1):89-9616814735
Cites: Diabetes Care. 1999 Sep;22(9):1462-7010480510
Cites: J Cell Sci. 2001 Aug;114(Pt 16):2903-1011686294
Cites: Adv Biol Regul. 2014 May;55:28-3824794538
Cites: Nat Genet. 2015 Jan;47(1):88-9125436857
Cites: Elife. 2014 Apr 25;3:e0138124771767
Cites: Development. 2005 Jul;132(13):2943-5415930105
Cites: Science. 2001 Jun 1;292(5522):1728-3111387480
Cites: Am J Hum Genet. 2014 Feb 6;94(2):223-3224507774
Cites: Science. 2004 May 28;304(5675):1325-815166380
Cites: J Intern Med. 2007 May;261(5):418-2517444881
Cites: PLoS Genet. 2015 Jan 27;11(1):e100487625625282
Cites: Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19368-7323134728
Cites: Nat Genet. 2007 Jul;39(7):906-1317572673
Cites: Diabetes. 2008 Apr;57(4):1120-418174525
Cites: Clin Cancer Res. 2001 Aug;7(8):2475-911489829
Cites: J Mol Med (Berl). 2009 Aug;87(8):825-3519554302
Cites: Bioinformatics. 2010 Sep 1;26(17):2190-120616382
Cites: Am J Hum Genet. 2013 Jul 11;93(1):42-5323768515
Cites: Genome Res. 2004 Jun;14(6):1188-9015173120
Cites: Diabetes. 2009 May;58(5):1212-2119223598
Cites: Genes Dev. 2003 Jun 1;17(11):1352-6512782654
Cites: J Biol Chem. 2001 Oct 19;276(42):38349-5211533044
Cites: Science. 2011 Oct 28;334(6055):47421979934
Cites: Stat Med. 2005 Oct 15;24(19):2911-3516152135
Cites: J Clin Endocrinol Metab. 2014 Feb;99(2):391-424285683
Cites: Cell Signal. 2008 Dec;20(12):2237-4618771725
Cites: Proteins. 2002 Aug 1;48(2):227-4112112692
Cites: Diabet Med. 1994 Apr;11(3):286-928033528
Cites: PLoS One. 2013 Jul 12;8(7):e6809523874508
Cites: Nat Genet. 2012 May 13;44(6):659-6922581228
Cites: Nature. 2006 Dec 14;444(7121):840-617167471
Cites: Nature. 2014 Aug 14;512(7513):190-325043022
Cites: Nature. 2016 Aug 4;536(7614):41-727398621
Cites: Am J Hum Genet. 2011 Jul 15;89(1):82-9321737059
Cites: Diabetes. 2003 Apr;52(4):910-712663460
Cites: JAMA. 2014 Jun 11;311(22):2305-1424915262
Cites: Nat Genet. 2014 Feb;46(2):200-424336170
Cites: Int J Epidemiol. 2010 Apr;39(2):504-1819959603
Cites: Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9350-519470471
Cites: J Clin Invest. 2003 Jul;112(2):197-20812843127
Cites: Nature. 2009 Nov 19;462(7271):307-1419924209
Cites: Science. 2015 May 8;348(6235):648-6025954001
Cites: Nucleic Acids Res. 2011 Jul;39(Web Server issue):W171-621459847
Cites: Nat Genet. 2010 Apr;42(4):348-5420208533
PubMed ID
28341696 View in PubMed
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Replication of putative candidate-gene associations with rheumatoid arthritis in >4,000 samples from North America and Sweden: association of susceptibility with PTPN22, CTLA4, and PADI4.

https://arctichealth.org/en/permalink/ahliterature13695
Source
Am J Hum Genet. 2005 Dec;77(6):1044-60
Publication Type
Article
Date
Dec-2005
Author
Robert M Plenge
Leonid Padyukov
Elaine F Remmers
Shaun Purcell
Annette T Lee
Elizabeth W Karlson
Frederick Wolfe
Daniel L Kastner
Lars Alfredsson
David Altshuler
Peter K Gregersen
Lars Klareskog
John D Rioux
Author Affiliation
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Source
Am J Hum Genet. 2005 Dec;77(6):1044-60
Date
Dec-2005
Language
English
Publication Type
Article
Keywords
Adult
Age of Onset
Alleles
Antigens, Differentiation - genetics
Arthritis, Rheumatoid - epidemiology - genetics
Case-Control Studies
Cohort Studies
Comparative Study
European Continental Ancestry Group - genetics - statistics & numerical data
Female
Genetic Predisposition to Disease - epidemiology - genetics
Humans
Hydrolases - genetics
Male
Middle Aged
North America - epidemiology
Odds Ratio
Protein-Tyrosine-Phosphatase - genetics
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Retrospective Studies
Review Literature
Sex Factors
Sweden - epidemiology
Variation (Genetics)
Abstract
Candidate-gene association studies in rheumatoid arthritis (RA) have lead to encouraging yet apparently inconsistent results. One explanation for the inconsistency is insufficient power to detect modest effects in the context of a low prior probability of a true effect. To overcome this limitation, we selected alleles with an increased probability of a disease association, on the basis of a review of the literature on RA and other autoimmune diseases, and tested them for association with RA susceptibility in a sample collection powered to detect modest genetic effects. We tested 17 alleles from 14 genes in 2,370 RA cases and 1,757 controls from the North American Rheumatoid Arthritis Consortium (NARAC) and the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) collections. We found strong evidence of an association of PTPN22 with the development of anti-citrulline antibody-positive RA (odds ratio [OR] 1.49; P=.00002), using previously untested EIRA samples. We provide support for an association of CTLA4 (CT60 allele, OR 1.23; P=.001) and PADI4 (PADI4_94, OR 1.24; P=.001) with the development of RA, but only in the NARAC cohort. The CTLA4 association is stronger in patients with RA from both cohorts who are seropositive for anti-citrulline antibodies (P=.0006). Exploration of our data set with clinically relevant subsets of RA reveals that PTPN22 is associated with an earlier age at disease onset (P=.004) and that PTPN22 has a stronger effect in males than in females (P=.03). A meta-analysis failed to demonstrate an association of the remaining alleles with RA susceptibility, suggesting that the previously published associations may represent false-positive results. Given the strong statistical power to replicate a true-positive association in this study, our results provide support for PTPN22, CTLA4, and PADI4 as RA susceptibility genes and demonstrate novel associations with clinically relevant subsets of RA.
PubMed ID
16380915 View in PubMed
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Use of a genetic isolate to identify rare disease variants: C7 on 5p associated with MS.

https://arctichealth.org/en/permalink/ahliterature152600
Source
Hum Mol Genet. 2009 May 1;18(9):1670-83
Publication Type
Article
Date
May-1-2009
Author
Suvi P Kallio
Eveliina Jakkula
Shaun Purcell
Minna Suvela
Keijo Koivisto
Pentti J Tienari
Irina Elovaara
Tuula Pirttilä
Mauri Reunanen
Denis Bronnikov
Markku Viander
Seppo Meri
Jan Hillert
Frida Lundmark
Hanne F Harbo
Aslaug R Lorentzen
Philip L De Jager
Mark J Daly
David A Hafler
Aarno Palotie
Leena Peltonen
Janna Saarela
Author Affiliation
Finnish Institute for Molecular Medicine, Biomedicum, Helsinki, Finland.
Source
Hum Mol Genet. 2009 May 1;18(9):1670-83
Date
May-1-2009
Language
English
Publication Type
Article
Keywords
Case-Control Studies
Chromosomes, Human, Pair 5 - genetics
Complement C7 - genetics
Finland
Genome-Wide Association Study
Haplotypes
Humans
Multiple Sclerosis - genetics
Abstract
Large case-control genome-wide association studies primarily expose common variants contributing to disease pathogenesis with modest effects. Thus, alternative strategies are needed to tackle rare, possibly more penetrant alleles. One strategy is to use special populations with a founder effect and isolation, resulting in allelic enrichment. For multiple sclerosis such a unique setting is reported in Southern Ostrobothnia in Finland, where the prevalence and familial occurrence of multiple sclerosis (MS) are exceptionally high. Here, we have studied one of the best replicated MS loci, 5p, and monitored for haplotypes shared among 72 regional MS cases, the majority of which are genealogically distantly related. The haplotype analysis over the 45 Mb region, covering the linkage peak identified in Finnish MS families, revealed only modest association at IL7R (P = 0.04), recently implicated in MS, whereas most significant association was found with one haplotype covering the C7-FLJ40243 locus (P = 0.0001), 5.1 Mb centromeric of IL7R. The finding was validated in an independent sample from the isolate and resulted in an odds ratio of 2.73 (P = 0.000003) in the combined data set. The identified relatively rare risk haplotype contains C7 (complement component 7), an important player of the innate immune system. Suggestive association with alleles of the region was seen also in more heterogeneous populations. Interestingly, also the complement activity correlated with the identified risk haplotype. These results suggest that the MS predisposing locus on 5p is more complex than assumed and exemplify power of population isolates in the identification of rare disease alleles.
Notes
Cites: Am J Hum Genet. 2001 Apr;68(4):978-8911254454
Cites: Ann Neurol. 2001 Jul;50(1):121-711456302
Cites: Ann Med. 2001 Sep;33(6):410-2111585102
Cites: J Immunol. 2002 Jan 1;168(1):458-6511751993
Cites: J Immunol. 2002 May 1;168(9):4293-30011970970
Cites: Glia. 2003 Jun;42(4):417-2312730962
Cites: Am J Hum Genet. 2003 Nov;73(5):1162-914574645
Cites: J Neuroimmunol. 2003 Oct;143(1-2):17-2414575909
Cites: J Neuroimmunol. 2003 Oct;143(1-2):129-3214575930
Cites: Lab Invest. 2004 Jan;84(1):21-814631387
Cites: Lancet Neurol. 2004 Feb;3(2):104-1014747002
Cites: Curr Opin Genet Dev. 2004 Jun;14(3):316-2315172676
Cites: Clin Neurol Neurosurg. 2004 Jun;106(3):175-915177766
Cites: Acta Neurol Scand. 1966;42(4):385-995919814
Cites: J Exp Med. 1970 Apr 1;131(4):629-414193934
Cites: Lancet. 1972 Jun 3;1(7762):1240-14113225
Cites: Acta Neurol Scand. 1975 Feb;51(2):85-981114880
Cites: Ann Neurol. 1983 Mar;13(3):227-316847134
Cites: Acta Neurol Scand. 1983 May;67(5):255-626880604
Cites: Ann Neurol. 1993 Mar;33(3):281-58498811
Cites: Neurology. 1994 Jan;44(1):11-58290043
Cites: J Immunol. 1995 May 1;154(9):4726-337536777
Cites: J Immunol. 1995 May 1;154(9):4734-407722325
Cites: Nat Genet. 1995 Jul;10(3):313-77545492
Cites: Nature. 1995 Sep 14;377(6545):150-17675080
Cites: Nat Genet. 1996 Aug;13(4):472-68696345
Cites: Nat Genet. 1996 Aug;13(4):477-808696346
Cites: Clin Exp Immunol. 1997 Jan;107(1):1-79010248
Cites: J Neurol Neurosurg Psychiatry. 1997 Jun;62(6):553-619219738
Cites: Am J Hum Genet. 1997 Dec;61(6):1379-879399895
Cites: Ann Neurol. 2000 Jun;47(6):707-1710852536
Cites: Clin Exp Immunol. 2000 Jul;121(1):69-7610886241
Cites: Acta Neurol Scand. 2001 Mar;103(3):153-811240562
Cites: J Neuroimmunol. 1998 Apr 1;84(1):69-759600710
Cites: J Neurol Sci. 1998 May 7;157(2):168-749619641
Cites: J Neuroimmunol. 1999 Sep 1;99(1):150-610496188
Cites: Ann Neurol. 1999 Oct;46(4):612-610514098
Cites: Hum Mutat. 2004 Dec;24(6):443-5915523646
Cites: Bioinformatics. 2005 Jan 15;21(2):263-515297300
Cites: J Immunol Methods. 2005 Jan;296(1-2):187-9815680163
Cites: Genes Immun. 2005 Mar;6(2):145-5215674389
Cites: Immunol Rev. 2005 Apr;204:208-3115790361
Cites: Genes Immun. 2005 Aug;6(5):375-8715973459
Cites: Twin Res Hum Genet. 2005 Aug;8(4):368-7516176722
Cites: Mult Scler. 2005 Oct;11(5):504-1016193885
Cites: J Neuroimmunol. 2005 Dec 30;170(1-2):122-3316169605
Cites: Nat Genet. 2006 May;38(5):556-6016582909
Cites: Clin Exp Immunol. 2006 Aug;145(2):219-2716879240
Cites: Am J Hum Genet. 2007 Sep;81(3):559-7517701901
Cites: Nat Genet. 2007 Sep;39(9):1108-1317660816
Cites: Nat Genet. 2007 Sep;39(9):1083-9117660817
Cites: N Engl J Med. 2007 Aug 30;357(9):851-6217660530
Cites: N Engl J Med. 2007 Aug 30;357(9):927-917660531
Cites: Ann N Y Acad Sci. 2007 Aug;1109:93-10517785294
Cites: N Engl J Med. 2007 Nov 22;357(21):2199-200; author reply 2200-118032773
Cites: N Engl J Med. 2008 Feb 14;358(7):753-418272905
Cites: Lancet Neurol. 2008 Jul;7(7):567-918565446
Cites: Ann Hum Genet. 2008 Jul;72(Pt 4):485-9818325082
Cites: Neuroepidemiology. 2000 Mar-Apr;19(2):67-7510686531
PubMed ID
19221116 View in PubMed
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