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1.  Genome-wide search for exonic variants affecting translational efficiency 
Nature communications  2013;4:2260.
The search for expression quantitative trait loci (eQTL) has traditionally centered entirely on the process of transcription, whereas variants with effects on mRNA translation have not been systematically studied. Here we present a high throughput approach for measuring translational cis-regulation in the human genome. Using ribosomal association as proxy for translational efficiency of polymorphic mRNAs, we test the ratio of polysomal/nonpolysomal mRNA level as a quantitative trait for association with single-nucleotide polymorphisms on the same mRNA transcript. We identify one important ribosomal-distribution effect, from rs1131017 in the 5’UTR of RPS26 , that is in high linkage disequilibrium (LD) with the 12q13 locus for susceptibility to type 1 diabetes. The effect on translation is confirmed at the protein level by quantitative Western blots, both ex vivo and after in vitro translation. Our results are a proof-of-principle that allelic effects on translation can be detected at a transcriptome-wide scale.
doi:10.1038/ncomms3260
PMCID: PMC3749366  PMID: 23900168
2.  The IRF5 polymorphism in type 1 diabetes 
Journal of Medical Genetics  2007;44(10):670-672.
The interferon regulatory factor 5 gene (IRF5) has been shown to play a crucial role in harmful immune responses by induction of proinflammatory cytokines. Functional genetic variants associated with increasd IRF5 expression of specific isoforms are associated with systemic lupus erythematosus (SLE) and it is possible that they may also predispose to other autoimmune disorders. We tested the association of two IRF5 SNPs, correlated with IRF5 expression and SLE risk, in 947 nuclear family trios type 1 diabetes (T1D) using the transmission disequilibrium test. Our results suggest that the functional IRF5 variations do not confer an obvious risk for T1D.
doi:10.1136/jmg.2007.050971
PMCID: PMC2597969  PMID: 17557928
3.  Study of Transcriptional Effects in Cis at the IFIH1 Locus 
PLoS ONE  2010;5(7):e11564.
Background
The Thr allele at the non-synonymous single-nucleotide polymorphism (nsSNP) Thr946Ala in the IFIH1 gene confers risk for Type 1 diabetes (T1D). The SNP is embedded in a 236 kb linkage disequilibrium (LD) block that includes four genes: IFIH1, GCA, FAP and KCNH7. The absence of common nsSNPs in the other genes makes the IFIH1 SNP the strongest functional candidate, but it could be merely a marker of association, due to LD with a variant regulating expression levels of IFIH1 or neighboring genes.
Methodology/Principal Findings
We investigated the effect of the T1D-associated variation on mRNA transcript expression of these genes. Heterozygous mRNA from lymphoblastoid cell lines (LCLs), pancreas and thymus was examined by allelic expression imbalance, to detect effects in cis on mRNA expression. Using single-nucleotide primer extension, we found no difference between mRNA transcripts in 9 LCLs, 6 pancreas and 13 thymus samples, suggesting that GCA and FAP are not involved. On the other hand, KCNH7 was not expressed at a detectable level in all tissues examined. Moreover, the association of the Thr946Ala SNP with T1D is not due to modulation of IFIH1 expression in organs involved in the disease, pointing to the IFIH1 nsSNP as the causal variant.
Conclusions/Significance
The mechanism of the association of the nsSNP with T1D remains to be determined, but does not involve mRNA modulation. It becomes necessary to study differential function of the IFIH1 protein alleles at Thr946Ala to confirm that it is responsible for the disease association.
doi:10.1371/journal.pone.0011564
PMCID: PMC2903489  PMID: 20644636
4.  Follow-Up Analysis of Genome-Wide Association Data Identifies Novel Loci for Type 1 Diabetes 
Diabetes  2009;58(1):290-295.
OBJECTIVE—Two recent genome-wide association (GWA) studies have revealed novel loci for type 1 diabetes, a common multifactorial disease with a strong genetic component. To fully utilize the GWA data that we had obtained by genotyping 563 type 1 diabetes probands and 1,146 control subjects, as well as 483 case subject–parent trios, using the Illumina HumanHap550 BeadChip, we designed a full stage 2 study to capture other possible association signals.
RESEARCH DESIGN AND METHODS—From our existing datasets, we selected 982 markers with P < 0.05 in both GWA cohorts. Genotyping these in an independent set of 636 nuclear families with 974 affected offspring revealed 75 markers that also had P < 0.05 in this third cohort. Among these, six single nucleotide polymorphisms in five novel loci also had P < 0.05 in the Wellcome Trust Case-Control Consortium dataset and were further tested in 1,303 type 1 diabetes probands from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) plus 1,673 control subjects.
RESULTS—Two markers (rs9976767 and rs3757247) remained significant after adjusting for the number of tests in this last cohort; they reside in UBASH3A (OR 1.16; combined P = 2.33 × 10−8) and BACH2 (1.13; combined P = 1.25 × 10−6).
CONCLUSIONS—Evaluation of a large number of statistical GWA candidates in several independent cohorts has revealed additional loci that are associated with type 1 diabetes. The two genes at these respective loci, UBASH3A and BACH2, are both biologically relevant to autoimmunity.
doi:10.2337/db08-1022
PMCID: PMC2606889  PMID: 18840781

Results 1-4 (4)