Genetic Epidemiology, Psychiatric Genetics, Asthma 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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PMID
22197932
TITLE
Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis.
ABSTRACT
Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16 population-based cohorts and then examined the ten most strongly associated new susceptibility loci in an additional 5,419 affected individuals and 19,833 controls from 14 studies. Three SNPs reached genome-wide significance in the discovery and replication cohorts combined, including rs479844 upstream of OVOL1 (odds ratio (OR) = 0.88, P = 1.1 × 10(-13)) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 × 10(-9)), both of which are near genes that have been implicated in epidermal proliferation and differentiation, as well as rs2897442 in KIF3A within the cytokine cluster at 5q31.1 (OR = 1.11, P = 3.8 × 10(-8)). We also replicated association with the FLG locus and with two recently identified association signals at 11q13.5 (rs7927894; P = 0.008) and 20q13.33 (rs6010620; P = 0.002). Our results underline the importance of both epidermal barrier function and immune dysregulation in atopic dermatitis pathogenesis.
DATE PUBLISHED
2012 Feb
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2011/07/08
accepted 2011/11/01
aheadofprint 2011/12/25
entrez 2011/12/27 06:00
pubmed 2011/12/27 06:00
medline 2012/03/31 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Paternoster L Paternoster Lavinia L Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK.
Standl M Standl Marie M
Chen CM Chen Chih-Mei CM
Ramasamy A Ramasamy Adaikalavan A
Bønnelykke K Bønnelykke Klaus K
Duijts L Duijts Liesbeth L
Ferreira MA Ferreira Manuel A MA
Alves AC Alves Alexessander Couto AC
Thyssen JP Thyssen Jacob P JP
Albrecht E Albrecht Eva E
Baurecht H Baurecht Hansjörg H
Feenstra B Feenstra Bjarke B
Sleiman PM Sleiman Patrick M A PM
Hysi P Hysi Pirro P
Warrington NM Warrington Nicole M NM
Curjuric I Curjuric Ivan I
Myhre R Myhre Ronny R
Curtin JA Curtin John A JA
Groen-Blokhuis MM Groen-Blokhuis Maria M MM
Kerkhof M Kerkhof Marjan M
Sääf A Sääf Annika A
Franke A Franke Andre A
Ellinghaus D Ellinghaus David D
Fölster-Holst R Fölster-Holst Regina R
Dermitzakis E Dermitzakis Emmanouil E
Montgomery SB Montgomery Stephen B SB
Prokisch H Prokisch Holger H
Heim K Heim Katharina K
Hartikainen AL Hartikainen Anna-Liisa AL
Pouta A Pouta Anneli A
Pekkanen J Pekkanen Juha J
Blakemore AI Blakemore Alexandra I F AI
Buxton JL Buxton Jessica L JL
Kaakinen M Kaakinen Marika M
Duffy DL Duffy David L DL
Madden PA Madden Pamela A PA
Heath AC Heath Andrew C AC
Montgomery GW Montgomery Grant W GW
Thompson PJ Thompson Philip J PJ
Matheson MC Matheson Melanie C MC
Le Souëf P Le Souëf Peter P
Australian Asthma Genetics Consortium (AAGC)
St Pourcain B St Pourcain Beate B
Smith GD Smith George Davey GD
Henderson J Henderson John J
Kemp JP Kemp John P JP
Timpson NJ Timpson Nicholas J NJ
Deloukas P Deloukas Panos P
Ring SM Ring Susan M SM
Wichmann HE Wichmann H-Erich HE
Müller-Nurasyid M Müller-Nurasyid Martina M
Novak N Novak Natalija N
Klopp N Klopp Norman N
Rodríguez E Rodríguez Elke E
McArdle W McArdle Wendy W
Linneberg A Linneberg Allan A
Menné T Menné Torkil T
Nohr EA Nohr Ellen A EA
Hofman A Hofman Albert A
Uitterlinden AG Uitterlinden André G AG
van Duijn CM van Duijn Cornélia M CM
Rivadeneira F Rivadeneira Fernando F
de Jongste JC de Jongste Johan C JC
van der Valk RJ van der Valk Ralf J P RJ
Wjst M Wjst Matthias M
Jogi R Jogi Rain R
Geller F Geller Frank F
Boyd HA Boyd Heather A HA
Murray JC Murray Jeffrey C JC
Kim C Kim Cecilia C
Mentch F Mentch Frank F
March M March Michael M
Mangino M Mangino Massimo M
Spector TD Spector Tim D TD
Bataille V Bataille Veronique V
Pennell CE Pennell Craig E CE
Holt PG Holt Patrick G PG
Sly P Sly Peter P
Tiesler CM Tiesler Carla M T CM
Thiering E Thiering Elisabeth E
Illig T Illig Thomas T
Imboden M Imboden Medea M
Nystad W Nystad Wenche W
Simpson A Simpson Angela A
Hottenga JJ Hottenga Jouke-Jan JJ
Postma D Postma Dirkje D
Koppelman GH Koppelman Gerard H GH
Smit HA Smit Henriette A HA
Söderhäll C Söderhäll Cilla C
Chawes B Chawes Bo B
Kreiner-Møller E Kreiner-Møller Eskil E
Bisgaard H Bisgaard Hans H
Melén E Melén Erik E
Boomsma DI Boomsma Dorret I DI
Custovic A Custovic Adnan A
Jacobsson B Jacobsson Bo B
Probst-Hensch NM Probst-Hensch Nicole M NM
Palmer LJ Palmer Lyle J LJ
Glass D Glass Daniel D
Hakonarson H Hakonarson Hakon H
Melbye M Melbye Mads M
Jarvis DL Jarvis Deborah L DL
Jaddoe VW Jaddoe Vincent W V VW
Gieger C Gieger Christian C
Genetics of Overweight Young Adults (GOYA) Consortium
Strachan DP Strachan David P DP
Martin NG Martin Nicholas G NG
Jarvelin MR Jarvelin Marjo-Riitta MR
Heinrich J Heinrich Joachim J
Evans DM Evans David M DM
Weidinger S Weidinger Stephan S
EArly Genetics & Lifecourse Epidemiology (EAGLE) Consortium
INVESTIGATORS
JOURNAL
VOLUME: 44
ISSUE: 2
TITLE: Nature genetics
ISOABBREVIATION: Nat. Genet.
YEAR: 2012
MONTH: Feb
DAY:
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
Meta-Analysis
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
068545 Wellcome Trust United Kingdom
076467 Wellcome Trust United Kingdom
084762 Wellcome Trust United Kingdom
092731 Wellcome Trust United Kingdom
G0401540 Medical Research Council United Kingdom
G0601361 Medical Research Council United Kingdom
G0601361(80219) Medical Research Council United Kingdom
G0800582 Medical Research Council United Kingdom
G0800582(86758) Medical Research Council United Kingdom
G9815508 Medical Research Council United Kingdom
G9815508(74882) Medical Research Council United Kingdom
K05 AA017688 NIAAA NIH HHS United States
MC_PC_15018 Medical Research Council United Kingdom
R01 DA012854 NIDA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Cell Differentiation genetics
Chromosomes, Human, Pair 11 genetics
Chromosomes, Human, Pair 20 genetics
Chromosomes, Human, Pair 5 genetics
Cytokines genetics
DNA-Binding Proteins genetics
Dermatitis, Atopic immunology
Epidermis immunology
Female immunology
Genetic Loci immunology
Genetic Predisposition to Disease immunology
Genome-Wide Association Study immunology
Humans immunology
Intermediate Filament Proteins genetics
Kinesin genetics
Male genetics
Polymorphism, Single Nucleotide genetics
Risk genetics
Transcription Factors genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Cytokines
0 DNA-Binding Proteins
0 Intermediate Filament Proteins
0 KIF3A protein, human
0 OVOL1 protein, human
0 Transcription Factors
0 filaggrin
EC 3.6.1.- Kinesin
OTHER ID's
OTHERID SOURCE
PMC3272375 NLM
UKMS37119 NLM