PMID- 23055271
OWN - NLM
STAT- MEDLINE
DCOM- 20130225
LR  - 20221207
IS  - 1531-8249 (Electronic)
IS  - 0364-5134 (Print)
IS  - 0364-5134 (Linking)
VI  - 72
IP  - 6
DP  - 2012 Dec
TI  - Risk for myasthenia gravis maps to a (151) Pro-->Ala change in TNIP1 and to human 
      leukocyte antigen-B*08.
PG  - 927-35
LID - 10.1002/ana.23691 [doi]
AB  - OBJECTIVE: The objective of this study is to comprehensively define the genetic 
      basis of early onset myasthenia gravis (EOMG). METHODS: We have carried out a 
      2-stage genome-wide association study on a total of 649 North European EOMG 
      patients. Cases were matched 1:4 with controls of European ancestry. We performed 
      imputation and conditional analyses across the major histocompatibility complex, 
      as well as in the top regions of association outside the human leukocyte antigen 
      (HLA) region. RESULTS: We observed the strongest association in the HLA class I 
      region at rs7750641 (p = 1.2 x 10(-92) ; odds ratio [OR], 6.25). By imputation 
      and conditional analyses, HLA-B*08 proves to be the major associated allele (p = 
      2.87 x 10(-113) ; OR, 6.41). In addition to the expected association with PTPN22 
      (rs2476601; OR, 1.71; p = 8.2 x 10(-10) ), an imputed coding variant (rs2233290) 
      at position 151 (Pro-->Ala) in the TNFAIP3-interacting protein 1, TNIP1, confers 
      even stronger risk than PTPN22 (OR, 1.91; p = 3.2 x 10(-10) ). INTERPRETATION: 
      The association at TNIP1 in EOMG implies disease mechanisms involving 
      ubiquitin-dependent dysregulation of NF-kappaB signaling. The localization of the 
      major HLA signal to the HLA-B*08 allele suggests that CD8(+) T cells may play a 
      key role in disease initiation or pathogenesis.
CI  - Copyright (c) 2012 American Neurological Association.
FAU - Gregersen, Peter K
AU  - Gregersen PK
AD  - Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institute for 
      Medical Research, North Shore LIJ Health System, Manhasset, NY 11030, USA. 
      peterg@nshs.edu
FAU - Kosoy, Roman
AU  - Kosoy R
FAU - Lee, Annette T
AU  - Lee AT
FAU - Lamb, Janine
AU  - Lamb J
FAU - Sussman, Jon
AU  - Sussman J
FAU - McKee, David
AU  - McKee D
FAU - Simpfendorfer, Kim R
AU  - Simpfendorfer KR
FAU - Pirskanen-Matell, Ritva
AU  - Pirskanen-Matell R
FAU - Piehl, Frederik
AU  - Piehl F
FAU - Pan-Hammarstrom, Qiang
AU  - Pan-Hammarstrom Q
FAU - Verschuuren, Jan J G M
AU  - Verschuuren JJ
FAU - Titulaer, Maarten J
AU  - Titulaer MJ
FAU - Niks, Erik H
AU  - Niks EH
FAU - Marx, Alexander
AU  - Marx A
FAU - Strobel, Philipp
AU  - Strobel P
FAU - Tackenberg, Bjorn
AU  - Tackenberg B
FAU - Putz, Michael
AU  - Putz M
FAU - Maniaol, Angelina
AU  - Maniaol A
FAU - Elsais, Ahmed
AU  - Elsais A
FAU - Tallaksen, Chantal
AU  - Tallaksen C
FAU - Harbo, Hanne F
AU  - Harbo HF
FAU - Lie, Benedicte A
AU  - Lie BA
FAU - Raychaudhuri, Soumya
AU  - Raychaudhuri S
FAU - de Bakker, Paul I W
AU  - de Bakker PI
FAU - Melms, Arthur
AU  - Melms A
FAU - Garchon, Henri-Jean
AU  - Garchon HJ
FAU - Willcox, Nicholas
AU  - Willcox N
FAU - Hammarstrom, Lennart
AU  - Hammarstrom L
FAU - Seldin, Michael F
AU  - Seldin MF
LA  - eng
GR  - R01 AI068759/AI/NIAID NIH HHS/United States
GR  - R01 AR062886/AR/NIAMS NIH HHS/United States
GR  - MRC_/Medical Research Council/United Kingdom
GR  - R01-AI-68759/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121010
PL  - United States
TA  - Ann Neurol
JT  - Annals of neurology
JID - 7707449
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HLA-B8 Antigen)
RN  - 0 (TNIP1 protein, human)
RN  - 9DLQ4CIU6V (Proline)
RN  - OF5P57N2ZX (Alanine)
SB  - IM
MH  - Adult
MH  - Age of Onset
MH  - Alanine/*genetics
MH  - Case-Control Studies
MH  - DNA-Binding Proteins/*genetics
MH  - Europe
MH  - Female
MH  - Gene Frequency
MH  - *Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Genotype
MH  - HLA-B8 Antigen/*genetics
MH  - Humans
MH  - Male
MH  - Meta-Analysis as Topic
MH  - Myasthenia Gravis/*genetics
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Proline/*genetics
MH  - White People/genetics
MH  - Young Adult
PMC - PMC3535539
MID - NIHMS392966
EDAT- 2012/10/12 06:00
MHDA- 2013/02/26 06:00
PMCR- 2013/12/01
CRDT- 2012/10/12 06:00
PHST- 2012/02/22 00:00 [received]
PHST- 2012/05/18 00:00 [revised]
PHST- 2012/06/13 00:00 [accepted]
PHST- 2012/10/12 06:00 [entrez]
PHST- 2012/10/12 06:00 [pubmed]
PHST- 2013/02/26 06:00 [medline]
PHST- 2013/12/01 00:00 [pmc-release]
AID - 10.1002/ana.23691 [doi]
PST - ppublish
SO  - Ann Neurol. 2012 Dec;72(6):927-35. doi: 10.1002/ana.23691. Epub 2012 Oct 10.