PMID- 20043853
OWN - NLM
STAT- MEDLINE
DCOM- 20100310
LR  - 20211020
IS  - 1755-8794 (Electronic)
IS  - 1755-8794 (Linking)
VI  - 2
DP  - 2009 Dec 31
TI  - Prioritizing genes for follow-up from genome wide association studies using 
      information on gene expression in tissues relevant for type 2 diabetes mellitus.
PG  - 72
LID - 10.1186/1755-8794-2-72 [doi]
AB  - BACKGROUND: Genome-wide association studies (GWAS) have emerged as a powerful 
      approach for identifying susceptibility loci associated with polygenetic diseases 
      such as type 2 diabetes mellitus (T2DM). However, it is still a daunting task to 
      prioritize single nucleotide polymorphisms (SNPs) from GWAS for further 
      replication in different population. Several recent studies have shown that 
      genetic variation often affects gene-expression at proximal (cis) as well as 
      distal (trans) genomic locations by different mechanisms such as altering rate of 
      transcription or splicing or transcript stability. METHODS: To prioritize SNPs 
      from GWAS, we combined results from two GWAS related to T2DM, the Diabetes 
      Genetics Initiative (DGI) and the Wellcome Trust Case Control Consortium (WTCCC), 
      with genome-wide expression data from pancreas, adipose tissue, liver and 
      skeletal muscle of individuals with or without T2DM or animal models thereof to 
      identify T2DM susceptibility loci. RESULTS: We identified 1,170 SNPs associated 
      with T2DM with P < 0.05 in both GWAS and 243 genes that were located in the 
      vicinity of these SNPs. Out of these 243 genes, we identified 115 differentially 
      expressed in publicly available gene expression profiling data. Notably five of 
      them, IGF2BP2, KCNJ11, NOTCH2, TCF7L2 and TSPAN8, have subsequently been shown to 
      be associated with T2DM in different populations. To provide further validation 
      of our approach, we reversed the approach and started with 26 known SNPs 
      associated with T2DM and related traits. We could show that 12 (57%) (HHEX, 
      HNF1B, IGF2BP2, IRS1, KCNJ11, KCNQ1, NOTCH2, PPARG, TCF7L2, THADA, TSPAN8 and 
      WFS1) out of 21 genes located in vicinity of these SNPs were showing aberrant 
      expression in T2DM from the gene expression profiling studies. CONCLUSIONS: 
      Utilizing of gene expression profiling data from different tissues of individuals 
      with or without T2DM or animal models thereof is a powerful tool for prioritizing 
      SNPs from WGAS for further replication studies.
FAU - Parikh, Hemang
AU  - Parikh H
AD  - Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, 
      University Hospital Malmo, Malmo, Sweden. parikhhm@mail.nih.gov
FAU - Lyssenko, Valeriya
AU  - Lyssenko V
FAU - Groop, Leif C
AU  - Groop LC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091231
PL  - England
TA  - BMC Med Genomics
JT  - BMC medical genomics
JID - 101319628
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Type 2/*genetics
MH  - Follow-Up Studies
MH  - *Gene Expression Profiling
MH  - *Genome-Wide Association Study
MH  - Humans
MH  - Mice
MH  - Oligonucleotide Array Sequence Analysis
MH  - Organ Specificity
MH  - Polymorphism, Single Nucleotide
MH  - Rats
MH  - Reproducibility of Results
PMC - PMC2815699
EDAT- 2010/01/02 06:00
MHDA- 2010/03/11 06:00
PMCR- 2009/12/31
CRDT- 2010/01/02 06:00
PHST- 2009/07/29 00:00 [received]
PHST- 2009/12/31 00:00 [accepted]
PHST- 2010/01/02 06:00 [entrez]
PHST- 2010/01/02 06:00 [pubmed]
PHST- 2010/03/11 06:00 [medline]
PHST- 2009/12/31 00:00 [pmc-release]
AID - 1755-8794-2-72 [pii]
AID - 10.1186/1755-8794-2-72 [doi]
PST - epublish
SO  - BMC Med Genomics. 2009 Dec 31;2:72. doi: 10.1186/1755-8794-2-72.