A gene-based pathway analysis using summary T1D meta-analysis GWAS statistics (7,514 cases and 9,045 controls).  Of the 1,583 tested pathways, 31 (2%) were identified to be enriched for association with T1D.  These pathways, and their genes,  were analysed to identify SNPs in or near these pathway genes that showed potentially novel T1D association.  In total 33 genes were selected with a minimum meta-analysis SNP P-value <10-4 with no previous T1D association reported.  Genotype data for additional sample existed for 22 of the selected 30 SNPs and 12 of these SNPs had replication P-values < 0.05. Although only 3 of these SNPs reach genomewide significance (P ≤ 5E-08), their membership of enriched pathways increases the prior for association.

Study Type
Case-Control Study
Exclusion Criteria

The samples that passed QC in Barrett et al. were included in this study - for further information please see study GDXHsS00004

Markers were excluded due to:-
  • Minor allele frequency (MAF) < 0.01
  • Missingness > 95%
  • Z2 HWE (controls) < 25
  • SNPs within the MHC region (chr6:25,000,000-35,000,000) were removed from all 3 datasets
  • Call rate ≤ 95%

Study Association

RegionLocationGene(s)MarkerAlleleMAFP ValueOdds Ratio
1p34.3chr1:35169091-36112344PSMB2  rs6703605C > T1.14e-05D 
1q21.3chr1:154298401-154658022IL6R  rs6427658C > T0.4283.26e-04C1.04 (0.96-1.13)D
1q24.3chr1:172681248-172875212FASLG  rs10912276A > G0.1743.60e-05C1.14 (1.02-1.27)D
1q31.3chr1:198570898-198877472PTPRC  rs2182419G > A0.1153.11e-05C1.12 (0.98-1.27)D
2q31.1chr2:172420749-172726125ITGA6  rs16860458A > G9.99e-05D 
3p25.2chr3:12438053-12819289RAF1  rs2450855G > A0.4623.10e-04C1.12 (1.05-1.19)D
4p14chr4:38726483-38905457TLR10  TLR6  rs4321646G > A7.72e-05D 
4q27chr4:121965085-122098465TRPC3  rs4502701A > C0.4813.32e-05C1.11 (1.04-1.18)D
5p13.2chr5:35799194-36037015IL7R  rs1445898C > T0.4292.76e-06C1.1 (1.03-1.16)D
5q33.1chr5:150653908-151007579DCTN4  rs4246045C > A0.1532.50e-04C1.48 (1.32-1.66)D
6p21.31chr6:35791157-36262301MAPK14  rs2237093C > T5.74e-05D 
6p25.3chr6:387659-468151IRF4  rs2048698T > C0.4852.76e-05C1.08 (0.99-1.16)D
6q21chr6:111645518-111984329FYN  rs11964650G > A0.0495.60e-07C1.09 (1.04-1.12)D
8p23.1chr8:11808009-11917029CTSB  rs1296023A > G0.3042.79e-07C1.11 (1.01-1.08)D
10p11.22chr10:32357176-33111134ITGB1  rs1557150A > G0.2821.93e-06C1.10 (1.02-1.18)D
10p11.22chr10:32983821-33222119NRP1  rs722988A > G0.3664.88e-08C1.11 (1.04-1.18)D
11p11.2chr11:46309432-48900510PSMC3  rs2293576G > A0.3273.14e-04C1.09 (1.01-1.16)D
11q13.1chr11:64076473-64456055BAD  rs694739T > C0.3682.37e-07C1.05 (0.98-1.12)D
11q23.3chr11:118154838-118441401JAML  rs11216829G > A0.2022.00e-04C1.15 (1.06-1.24)D
12q13.2chr12:55957562-56397446DGKA  rs11171710G > A7.23e-22D 
12q13.13chr12:53058065-53209207ITGB7  rs11170466C > T0.0487.86e-09C1.19 (0.99-1.44)D
13q12.3chr13:30414075-30483545HMGB1  rs1360485A > G0.2942.24e-04C1.14 (1.06-1.22)D
13q32.1chr13:95491874-96360521DNAJC3  rs9302086C > T5.81e-05D 
14q23.1chr14:61536085-61577374PRKCH  rs1111107A > G1.32e-05D 
17p13.1chr17:7715286-7817540TP53  rs16956936C > T0.1269.60e-07C1.3 (1.27-1.47)D
17p13.2chr17:3955589-4419999UBE2G1  rs9906760A > G0.3305.08e-07C1.09 (1.02-1.16)D
17q21.31chr17:45217032-45573674MAP3K14  rs17759555C > A0.3099.67e-07C1.11 (1.01-1.20)D
19q13.32chr19:47045031-47255671SAE1  rs411560T > C4.69e-05D 


GDXHsS00042 meets the following criteria:

Criteria Name
Disease Tags
Study for a Disease 


PMIDTitleFirst AuthorJournalDisease(s)Date