Genome wide identification of new genes and pathways in XXXX with both autoimmune thyroiditis and type 1 diabetes.

@entity1 @entity1669 @entity2936 @entity1723 @entity72031 @entity12010 @entity5812 @entity4386
@entity1669 ( @entity1669 ) and @entity1723 ( @entity1723 ) frequently occur in the same individual pointing to a strong shared genetic susceptibility. Indeed, the co-occurrence of @entity1723 and @entity1669 in the same individual is classified as a variant of the @entity12010 type 3 (designated APS3v). Our aim was to identify new genes and mechanisms causing the co-occurrence of @entity1723 + @entity1669 (APS3v) in the same individual using a genome-wide approach. For our discovery set we analyzed 346 Caucasian APS3v @entity1 and 727 gender and ethnicity matched healthy controls. Genotyping was performed using the Illumina Human660W-Quad.v1. The replication set included 185 APS3v @entity1 and 340 controls. Association analyses were performed using the PLINK program, and pathway analyses were performed using the MAGENTA software. We identified multiple signals within the HLA region and conditioning studies suggested that a few of them contributed independently to the strong association of the HLA locus with APS3v. Outside the HLA region, variants in @entity72031 , a gene not suggested by previous studies of APS3v, @entity1723 , or @entity1669 , showed genome-wide significance (p < 5 * 10(-8)). In addition, a locus on 1p13 containing the @entity5812 gene showed genome-wide significant associations. Pathway analysis demonstrated that cell cycle, B-cell development, @entity2936 , and @entity4386 signaling were the major pathways contributing to the pathogenesis of APS3v. These findings suggest that complex mechanisms involving T-cell and B-cell pathways are involved in the strong genetic association between @entity1669 and @entity1723 .
