Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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22504421
TITLE
Common variants at 12q14 and 12q24 are associated with hippocampal volume.
ABSTRACT
Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimer's disease and vascular risk factors. Our genome-wide association study (GWAS) of dementia-free persons (n = 9,232) identified 46 SNPs at four loci with P values of <4.0 × 10(-7). In two additional samples (n = 2,318), associations were replicated at 12q14 within MSRB3-WIF1 (discovery and replication; rs17178006; P = 5.3 × 10(-11)) and at 12q24 near HRK-FBXW8 (rs7294919; P = 2.9 × 10(-11)). Remaining associations included one SNP at 2q24 within DPP4 (rs6741949; P = 2.9 × 10(-7)) and nine SNPs at 9p33 within ASTN2 (rs7852872; P = 1.0 × 10(-7)); along with the chromosome 12 associations, these loci were also associated with hippocampal volume (P < 0.05) in a third younger, more heterogeneous sample (n = 7,794). The SNP in ASTN2 also showed suggestive association with decline in cognition in a largely independent sample (n = 1,563). These associations implicate genes related to apoptosis (HRK), development (WIF1), oxidative stress (MSR3B), ubiquitination (FBXW8) and neuronal migration (ASTN2), as well as enzymes targeted by new diabetes medications (DPP4), indicating new genetic influences on hippocampal size and possibly the risk of cognitive decline and dementia.
DATE PUBLISHED
2012 Apr 15
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2011/09/06
accepted 2012/03/06
entrez 2012/04/17 06:00
pubmed 2012/04/17 06:00
medline 2012/07/03 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Bis JC Bis Joshua C JC Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
DeCarli C DeCarli Charles C
Smith AV Smith Albert Vernon AV
van der Lijn F van der Lijn Fedde F
Crivello F Crivello Fabrice F
Fornage M Fornage Myriam M
Debette S Debette Stephanie S
Shulman JM Shulman Joshua M JM
Schmidt H Schmidt Helena H
Srikanth V Srikanth Velandai V
Schuur M Schuur Maaike M
Yu L Yu Lei L
Choi SH Choi Seung-Hoan SH
Sigurdsson S Sigurdsson Sigurdur S
Verhaaren BF Verhaaren Benjamin F J BF
DeStefano AL DeStefano Anita L AL
Lambert JC Lambert Jean-Charles JC
Jack CR Jr Jack Clifford R CR
Struchalin M Struchalin Maksim M
Stankovich J Stankovich Jim J
Ibrahim-Verbaas CA Ibrahim-Verbaas Carla A CA
Fleischman D Fleischman Debra D
Zijdenbos A Zijdenbos Alex A
den Heijer T den Heijer Tom T
Mazoyer B Mazoyer Bernard B
Coker LH Coker Laura H LH
Enzinger C Enzinger Christian C
Danoy P Danoy Patrick P
Amin N Amin Najaf N
Arfanakis K Arfanakis Konstantinos K
van Buchem MA van Buchem Mark A MA
de Bruijn RF de Bruijn Renée F A G RF
Beiser A Beiser Alexa A
Dufouil C Dufouil Carole C
Huang J Huang Juebin J
Cavalieri M Cavalieri Margherita M
Thomson R Thomson Russell R
Niessen WJ Niessen Wiro J WJ
Chibnik LB Chibnik Lori B LB
Gislason GK Gislason Gauti K GK
Hofman A Hofman Albert A
Pikula A Pikula Aleksandra A
Amouyel P Amouyel Philippe P
Freeman KB Freeman Kevin B KB
Phan TG Phan Thanh G TG
Oostra BA Oostra Ben A BA
Stein JL Stein Jason L JL
Medland SE Medland Sarah E SE
Vasquez AA Vasquez Alejandro Arias AA
Hibar DP Hibar Derrek P DP
Wright MJ Wright Margaret J MJ
Franke B Franke Barbara B
Martin NG Martin Nicholas G NG
Thompson PM Thompson Paul M PM
Enhancing Neuro Imaging Genetics through Meta-Analysis Consortium
Nalls MA Nalls Michael A MA
Uitterlinden AG Uitterlinden Andre G AG
Au R Au Rhoda R
Elbaz A Elbaz Alexis A
Beare RJ Beare Richard J RJ
van Swieten JC van Swieten John C JC
Lopez OL Lopez Oscar L OL
Harris TB Harris Tamara B TB
Chouraki V Chouraki Vincent V
Breteler MM Breteler Monique M B MM
De Jager PL De Jager Philip L PL
Becker JT Becker James T JT
Vernooij MW Vernooij Meike W MW
Knopman D Knopman David D
Fazekas F Fazekas Franz F
Wolf PA Wolf Philip A PA
van der Lugt A van der Lugt Aad A
Gudnason V Gudnason Vilmundur V
Longstreth WT Jr Longstreth W T WT
Brown MA Brown Matthew A MA
Bennett DA Bennett David A DA
van Duijn CM van Duijn Cornelia M CM
Mosley TH Mosley Thomas H TH
Schmidt R Schmidt Reinhold R
Tzourio C Tzourio Christophe C
Launer LJ Launer Lenore J LJ
Ikram MA Ikram M Arfan MA
Seshadri S Seshadri Sudha S
Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Stein Jason L JL
Medland Sarah E SE
Arias Vasquez Alejandro A
Hibar Derrek P DP
Senstad Rudy E RE
Winkler Anderson M AM
Toro Roberto R
Appel Katja K
Bartecek Richard R
Bergmann Ørjan Ø
Bernard Manon M
Brown Andrew A AA
Cannon Dara M DM
Chakravarty Mallar M
Christoforou Andrea A
Domin Martin M
Grimm Oliver O
Hollinshead Marisa M
Holmes Avram J AJ
Homuth Georg G
Hottenga Jouke-Jan JJ
Langan Camilla C
Lopez Lorna M LM
Hansell Narelle K NK
Hwang Kristy S KS
Kim Sungeun S
Laje Gonzalo G
Lee Phil H PH
Liu Xinmin X
Loth Eva E
Lourdusamy Anbarasu A
Maniega Susana Muñoz SM
Mattingsdal Morten M
Mohnke Sebastian S
Nho Kwangsik K
Nugent Allison C AC
O'Brien Carol C
Papmeyer Martina M
Pütz Benno B
Ramasamy Adaikalavan A
Rasmussen Jerod J
Rijpkema Mark M
Risacher Shannon L SL
Roddey J Cooper JC
Rose Emma J EJ
Ryten Mina M
Shen Li L
Sprooten Emma E
Strengman Eric E
Teumer Alexander A
Trabzuni Daniah D
Turner Jessica J
van Eijk Kristel K
van Erp Theo G M TG
van Tol Marie-Jose MJ
Wittfeld Katharina K
Wolf Christiane C
Woudstra Saskia S
Aleman Andre A
Alhusaini Saud S
Almasy Laura L
Binder Elisabeth B EB
Brohawn David G DG
Cantor Rita M RM
Carless Melanie A MA
Corvin Aiden A
Czisch Michael M
Curran Joanne E JE
Davies Gail G
de Almeida Marcio A A MA
Delanty Norman N
Depondt Chantal C
Duggirala Ravi R
Dyer Thomas D TD
Erk Susanne S
Fagerness Jesen J
Fox Peter T PT
Freimer Nelson B NB
Gill Michael M
Göring Harald H H HH
Hagler Donald J DJ
Hoehn David D
Holsboer Florian F
Hoogman Martine M
Hosten Norbert N
Jahanshad Neda N
Johnson Matthew P MP
Kasperaviciute Dalia D
Kent Jack W JW
Kochunov Peter P
Lancaster Jack L JL
Lawrie Stephen M SM
Liewald David C DC
Mandl René R
Matarin Mar M
Mattheisen Manuel M
Meisenzahl Eva E
Melle Ingrid I
Moses Eric K EK
Mühleisen Thomas W TW
Nauck Matthias M
Nöthen Markus M MM
Olvera Rene L RL
Pandolfo Massimo M
Pike G Bruce GB
Puls Ralf R
Reinvang Ivar I
Rentería Miguel E ME
Rietschel Marcella M
Roffman Joshua L JL
Royle Natalie A NA
Rujescu Dan D
Savitz Jonathan J
Schnack Hugo G HG
Schnell Knut K
Seiferth Nina N
Smith Colin C
Steen Vidar M VM
Valdés Hernández Maria C MC
Van den Heuvel Martijn M
van der Wee Nic J NJ
Van Haren Neeltje E M NE
Veltman Joris A JA
Völzke Henry H
Walker Robert R
Westlye Lars T LT
Whelan Christopher D CD
Agartz Ingrid I
Boomsma Dorret I DI
Cavalleri Gianpiero L GL
Dale Anders M AM
Djurovic Srdjan S
Drevets Wayne C WC
Hagoort Peter P
Hall Jeremy J
Heinz Andreas A
Jack Clifford R CR
Foroud Tatiana M TM
Le Hellard Stephanie S
Macciardi Fabio F
Montgomery Grant W GW
Poline Jean Baptiste JB
Porteous David J DJ
Sisodiya Sanjay M SM
Starr John M JM
Sussmann Jessika J
Toga Arthur W AW
Veltman Dick J DJ
Walter Henrik H
Weiner Michael W MW
Andreassen Ole A OA
Apostolova Liana G LG
Bastin Mark E ME
Blangero John J
Brunner Han G HG
Buckner Randy L RL
Cichon Sven S
Coppola Giovanni G
de Zubicaray Greig I GI
Deary Ian J IJ
Donohoe Gary G
de Geus Eco J C EJ
Espeseth Thomas T
Fernández Guillén G
Glahn David C DC
Grabe Hans J HJ
Hardy John J
Hulshoff Pol Hilleke E HE
Jenkinson Mark M
Kahn René S RS
McDonald Colm C
McIntosh Andrew M AM
McMahon Francis J FJ
McMahon Katie L KL
Meyer-Lindenberg Andreas A
Morris Derek W DW
Müller-Myhsok Bertram B
Nichols Thomas E TE
Ophoff Roel A RA
Paus Tomas T
Pausova Zdenka Z
Penninx Brenda W BW
Potkin Steven G SG
Sämann Philipp G PG
Saykin Andrew J AJ
Schumann Gunter G
Smoller Jordan W JW
Wardlaw Joanna M JM
Weale Michael E ME
Martin Nicholas G NG
Franke Barbara B
Wright Margaret J MJ
Thompson Paul M PM
JOURNAL
VOLUME: 44
ISSUE: 5
TITLE: Nature genetics
ISOABBREVIATION: Nat Genet
YEAR: 2012
MONTH: Apr
DAY: 15
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Alzheimer Disease genetics
Chromosomes, Human, Pair 12 genetics
Cognition Disorders genetics
Dementia genetics
Genetic Loci genetics
Genetic Markers genetics
Genome-Wide Association Study genetics
Hippocampus physiopathology
Humans physiopathology
Meta-Analysis as Topic physiopathology
Polymorphism, Single Nucleotide genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Genetic Markers
OTHER ID's
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