PMID- 22976473
OWN - NLM
STAT- MEDLINE
DCOM- 20130405
LR  - 20211021
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 21
IP  - R1
DP  - 2012 Oct 15
TI  - Interrogating the major histocompatibility complex with high-throughput genomics.
PG  - R29-36
AB  - The major histocompatibility complex (MHC) region on the short arm of chromosome 
      6 harbors the largest number of replicated associations across the human genome 
      for a wide range of diseases, but the functional basis for these associations is 
      still poorly understood. One fundamental challenge in fine-mapping associations 
      to functional alleles is the enormous sequence diversity and broad linkage 
      disequilibrium of the MHC, both of which hamper the cost-effective interrogation 
      in large patient samples and the identification of causal variants. In this 
      review, we argue that there is now a valuable opportunity to leverage existing 
      genome-wide association study (GWAS) datasets for in-depth investigation to 
      identify independent effects in the MHC. Application of imputation to GWAS data 
      facilitates comprehensive interrogation of the classical human leukocyte antigen 
      (HLA) loci. These datasets are, in many cases, sufficiently large to give 
      investigators the ability to disentangle effects at different loci. We also 
      explain how querying variation at individual amino acid positions for association 
      can be powerful and expand traditional analyses that focus only on the classical 
      HLA types.
FAU - de Bakker, Paul I W
AU  - de Bakker PI
AD  - Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The 
      Netherlands. pdebakker@umcutrecht.nl
FAU - Raychaudhuri, Soumya
AU  - Raychaudhuri S
LA  - eng
GR  - 1 R01 AR062886-01/AR/NIAMS NIH HHS/United States
GR  - 5K08AR055688/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20120912
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Amino Acid Sequence
MH  - *Chromosome Mapping
MH  - Databases, Nucleic Acid
MH  - *Genetic Predisposition to Disease
MH  - Genetic Variation
MH  - Genome, Human
MH  - Genome-Wide Association Study
MH  - HLA Antigens/*genetics
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - Linkage Disequilibrium/genetics
MH  - Major Histocompatibility Complex/*genetics
PMC - PMC3459647
EDAT- 2012/09/15 06:00
MHDA- 2013/04/06 06:00
PMCR- 2013/10/15
CRDT- 2012/09/15 06:00
PHST- 2012/09/15 06:00 [entrez]
PHST- 2012/09/15 06:00 [pubmed]
PHST- 2013/04/06 06:00 [medline]
PHST- 2013/10/15 00:00 [pmc-release]
AID - dds384 [pii]
AID - 10.1093/hmg/dds384 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2012 Oct 15;21(R1):R29-36. doi: 10.1093/hmg/dds384. Epub 2012 Sep 
      12.