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1.  Association Between a Functional Variant Downstream of TNFAIP3 and Systemic Lupus Erythematosus 
Nature genetics  2011;43(3):253-258.
Systemic Lupus Erythematosus (SLE, OMIM 152700) is an autoimmune disease characterized by self-reactive antibodies resulting in systemic inflammation and organ failure. TNFAIP3, encoding the ubiquitin-modifying enzyme A20, is an established susceptibility locus for SLE. By fine mapping and genomic resequencing in ethnically diverse populations we fully characterized the TNFAIP3 risk haplotype and isolated a novel TT>A polymorphic dinucleotide associated with SLE in subjects of European (P = 1.58 × 10−8; odds ratio (OR) = 1.70) and Korean (P = 8.33 × 10−10; OR = 2.54) ancestry. This variant, located in a region of high conservation and regulatory potential, bound a nuclear protein complex comprised of NF-κB subunits with reduced avidity. Furthermore, compared with the non-risk haplotype, the haplotype carrying this variant resulted in reduced TNFAIP3 mRNA and A20 protein expression. These results establish this TT>A variant as the most likely functional polymorphism responsible for the association between TNFAIP3 and SLE.
doi:10.1038/ng.766
PMCID: PMC3103780  PMID: 21336280
2.  Mutations in the formin protein INF2 cause focal segmental glomerulosclerosis 
Nature genetics  2009;42(1):72-76.
Focal segmental glomerulosclerosis (FSGS) is a pattern of kidney injury observed either as an idiopathic finding or as a consequence of underlying systemic conditions. Several genes have been identified which, when mutated, lead to inherited FSGS and/or the nephrotic syndrome. These findings have accelerated the understanding of glomerular podocyte function and disease, motivating our search for additional FSGS genes. Using linkage analysis, we identified a locus for autosomal dominant FSGS on a region of chromosome 14q. By sequencing multiple genes in this region, we detected nine independent non-conservative missense mutations in INF2, which encodes a member of the formin family of actin regulating proteins. These mutations, all within the diaphanous inhibitory domain, segregate with disease in 11 unrelated families and alter highly conserved amino acid residues. The observation that mutations in this podocyte-expressed formin cause FSGS highlights the importance of fine regulation of actin polymerization in podocyte function.
doi:10.1038/ng.505
PMCID: PMC2980844  PMID: 20023659
3.  A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus 
Nature genetics  2009;41(11):1228-1233.
Genome-wide association studies have recently identified at least 15 susceptibility loci for systemic lupus erythematosus (SLE). To confirm additional risk loci, we selected SNPs from 2,466 regions that showed nominal evidence of association to SLE (P < 0.05) in a genome-wide study and genotyped them in an independent sample of 1,963 cases and 4,329 controls. This replication effort identified five new SLE susceptibility loci (P < 5 × 10−8): TNIP1 (odds ratio (OR) = 1.27), PRDM1 (OR = 1.20), JAZF1 (OR = 1.20), UHRF1BP1 (OR = 1.17) and IL10 (OR = 1.19). We identified 21 additional candidate loci with P ≤ 1 × 10−5. A candidate screen of alleles previously associated with other autoimmune diseases suggested five loci (P < 1 × 10−3) that may contribute to SLE: IFIH1, CFB, CLEC16A, IL12B and SH2B3. These results expand the number of confirmed and candidate SLE susceptibility loci and implicate several key immunologic pathways in SLE pathogenesis.
doi:10.1038/ng.468
PMCID: PMC2925843  PMID: 19838195

Results 1-3 (3)