PMID- 21076979
OWN - NLM
STAT- MEDLINE
DCOM- 20110207
LR  - 20211020
IS  - 1432-1203 (Electronic)
IS  - 0340-6717 (Print)
IS  - 0340-6717 (Linking)
VI  - 129
IP  - 2
DP  - 2011 Feb
TI  - Conditional meta-analysis stratifying on detailed HLA genotypes identifies a 
      novel type 1 diabetes locus around TCF19 in the MHC.
PG  - 161-76
LID - 10.1007/s00439-010-0908-2 [doi]
AB  - The human leukocyte antigen (HLA) class II genes HLA-DRB1, -DQA1 and -DQB1 are 
      the strongest genetic factors for type 1 diabetes (T1D). Additional loci in the 
      major histocompatibility complex (MHC) are difficult to identify due to the 
      region's high gene density and complex linkage disequilibrium (LD). To facilitate 
      the association analysis, two novel algorithms were implemented in this study: 
      one for phasing the multi-allelic HLA genotypes in trio families, and one for 
      partitioning the HLA strata in conditional testing. Screening and replication 
      were performed on two large and independent datasets: the Wellcome Trust 
      Case-Control Consortium (WTCCC) dataset of 2,000 cases and 1,504 controls, and 
      the T1D Genetics Consortium (T1DGC) dataset of 2,300 nuclear families. After 
      imputation, the two datasets have 1,941 common SNPs in the MHC, of which 22 were 
      successfully tested and replicated based on the statistical testing stratifying 
      on the detailed DRB1 and DQB1 genotypes. Further conditional tests using the 
      combined dataset confirmed eight novel SNP associations around 31.3 Mb on 
      chromosome 6 (rs3094663, p = 1.66 x 10(-11) and rs2523619, p = 2.77 x 10(-10) 
      conditional on the DR/DQ genotypes). A subsequent LD analysis established TCF19, 
      POU5F1, CCHCR1 and PSORS1C1 as potential causal genes for the observed 
      association.
FAU - Cheung, Yee Him
AU  - Cheung YH
AD  - Department of Electrical Engineering, Center for Computational Biology and 
      Bioinformatics, Columbia University, 1300 S.W. Mudd, 500 West 120th Street, New 
      York, NY 10027, USA.
FAU - Watkinson, John
AU  - Watkinson J
FAU - Anastassiou, Dimitris
AU  - Anastassiou D
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - U01 DK062418/DK/NIDDK NIH HHS/United States
GR  - 076113/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101114
PL  - Germany
TA  - Hum Genet
JT  - Human genetics
JID - 7613873
RN  - 0 (CCHCR1 protein, human)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Octamer Transcription Factor-3)
RN  - 0 (POU5F1 protein, human)
RN  - 0 (PSORS1C1 protein, human)
RN  - 0 (Proteins)
RN  - 0 (TCF19 protein, human)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Case-Control Studies
MH  - Diabetes Mellitus, Type 1/*genetics
MH  - Female
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/genetics
MH  - Male
MH  - Octamer Transcription Factor-3/genetics
MH  - *Polymorphism, Single Nucleotide
MH  - Proteins/genetics
MH  - Transcription Factors/*genetics
PMC - PMC3020293
EDAT- 2010/11/16 06:00
MHDA- 2011/02/08 06:00
PMCR- 2010/11/14
CRDT- 2010/11/16 06:00
PHST- 2010/09/10 00:00 [received]
PHST- 2010/10/26 00:00 [accepted]
PHST- 2010/11/16 06:00 [entrez]
PHST- 2010/11/16 06:00 [pubmed]
PHST- 2011/02/08 06:00 [medline]
PHST- 2010/11/14 00:00 [pmc-release]
AID - 908 [pii]
AID - 10.1007/s00439-010-0908-2 [doi]
PST - ppublish
SO  - Hum Genet. 2011 Feb;129(2):161-76. doi: 10.1007/s00439-010-0908-2. Epub 2010 Nov 
      14.