A meta-analysis by combining data from two genome-wide association studies (GWAS), and replication with supplemented ImmunoChip data for a total of 3,096 cases and 7,489 controls in individuals of US and Central European population.
Whole-genome genotyping for the meta-analysis was performed on either Illumina HumanHap550 BeadChip or the Illumina Omni express. The replication cohort was genotyped with the Illumina Immunochip. Additionally, SNPs selected for replicaion, which were not present on the ImmunoChip, were genotyped on the MassArray system using a Sequenom Compact MALDI-TOF device and iPLEX Gold reagents in multiplex reactions. Imputation was performed with CEU + TSI HapMap phase 3 data (UCSC hg18/NCBI 36) using Beagle v3.13. Relatedness and association testing was done with PLINK. All statistical analyses were performed in R version 3.0.1.
The combined analysis identified two novel loci, outside the MHC, that exceed the gwas statistical signicance threshold of (P < 5 X 10-8) and a third nominally significant region. The study also confirms the previous known risk loci, increasing the total number of confirmed AA risk loci to 14 (including the MHC region).
Study Type
Whole Genome Association Study
Exclusion Criteria
Samples were excluded due to :-
  • Call rate < 0.90
  • Missing rate per individual < 0.02
  • Heterozygosity per individual  ±2 (Fhet, statistic, standardized values in plink)
Markers were excluded due to :-
  • Call rate < 0.90
  • Missing rate per SNP < 0.05 (before sample removal), SNP < 0.02 (after sample removal)
  • Hardy-Weinberg equilibrium P < 10-6 (in controls),  P < 10-10 (in cases)
  • LD (r2 > 0.05)
  • Minor allele frequency (MAF) <0.05%

Study Association

RegionLocationGene(s)MarkerAlleleMAFP ValueOdds Ratio
1p13.2chr1:113296527-114009223PTPN22  rs2476601G > A0.0908.90e-08C1.34C
2q13chr2:110687307-111051453BCL2L11  ACOXL  rs3789129A > C0.1801.50e-08C1.32C
2q33.2chr2:203750711-203951852CTLA4  CD28  ICOS  rs231775A > G0.3802.20e-20C1.39C
4q27chr4:122061159-122684373IL2  IL21  rs7682481G > C0.3304.80e-09C1.23C
5q31.1chr5:132447521-132799680IL13  IL4  rs848C > A0.2104.80e-09C1.27C
6q25.1chr6:149977706-150128432RAET1L  ULBP3  rs9479478T > G0.4505.90e-24C1.49C
9q31.1chr9:99518831-100406715NR4A3  STX17  rs10124366A > G0.2601.10e-05C1.20C
10p15.1chr10:5988280-6131453IL2RA  IL15RA  rs3118470T > C0.3107.70e-21C1.41C
11q13.1chr11:64076473-64456055PRDX5  rs574087A > G0.4808.70e-14C1.33C
11q13.5chr11:76324636-76632292LRRC32  rs2155219G > T0.5004.10e-08C1.21C
12q13.2chr12:55958153-56404651ERBB3  IKZF4  rs2292239G > T0.3204.40e-09C1.25C
12q24.12chr12:111284392-112592683ATXN2  SH2B3  rs653178C > T0.5001.60e-07C1.19C
16p13.13chr16:10923201-11220282CIITA  CLEC16A  SOCS1  rs3862469C > T0.3301.70e-07C1.22C
MHCchr6:32611966-32767729HLA-DQB1  rs9275524C > T0.4201.80e-60C1.92C


GDXHsS00045 meets the following criteria:

Criteria Name
Disease Tags
Study for a Disease 


PMIDTitleFirst AuthorJournalDisease(s)Date