Overview

A 2 stage genome-wide meta analysis including 6 T1D cohorts was conducted.  In the discovery phase, using imputation (Mach 1.0) with HapMap CEU population, a total of ~2.4M variants were analysed using logistic regression on Affymetrix platforms and ~2M using Ilumina platforms. PLINK was utilised to combine samples across platforms using inverse-variance meta-analysis. After QC and a fixed effect meta-analysis , 53 variants were chosen for replication in a parent trio cohort using TDT as implemented in PLINK. Having combined discovery and replication meta-analysis p-values using Fisher's method (Haploview),three variants achieved genome-wide significance (P <10-8) and identified genomic regions of T1D susceptibility that had not been previously reported.

Study Type
Whole Genome Association Study
Samples
GroupPhenotypePopulationCasesControlsFamiliesTrios
DiscoveryT1D993416956--
ReplicationT1D---1120
Exclusion Criteria

Sample

  • Genotyping call rate < 98%
  • Cryptic relatedness

SNP

  • MAF < 1%
  • Genotyping call rate < 95 %
  • Deviation from HWE P <= 0.00001

Study Association

RegionLocationGene(s)MarkerAlleleMAFP ValueOdds Ratio
1p13.2chr1:113296527-114009223PTPN22  rs2476601G > A5.93e-80D1.96D
1p31.3chr1:63635737-63707138rs2269245G > A4.47e-06C1.16D
1p36.22chr1:12159853-12208442rs235219G > A1.26e-05C1.19D
1q31.2chr1:192500477-192578911RGS1  rs2209014A > G2.16e-04D1.12D
1q32.1chr1:206736652-206867593IL10  rs3024493C > A2.01e-08D1.22D
1q32.3chr1:212668617-212927263rs6681171T > G1.41e-05C1.18D
2p13.3chr2:68409791-68653154rs7420089C > T2.27e-05C1.47D
2p23.2chr2:28377859-28450325FOSL2  rs6547853G > A7.54e-07C1.12D
2p23.3chr2:24795892-25264789EFR3B  rs478222A > T3.50e-09C1.15D
2q11.2chr2:99928492-100425222AFF3  rs6740838G > T5.12e-06D1.12D
2q13chr2:111886554-112181465rs4848967G > A5.04e-05C1.18D
2q24.2chr2:162104363-162504293IFIH1  rs1990760T > C2.21e-08D1.15D
2q32.3chr2:191058115-191166537STAT4  rs6744380G > A1.22e-04D1.10D
2q33.2chr2:203749263-203951852CTLA4  rs11571316G > A2.44e-15D1.22D
3p21.31chr3:46430248-46623418CCR5  rs17078977C > T4.03e-04D1.15D
3q26.1chr3:165716004-166218782rs1839308G > C3.60e-05C1.2D
4p15.2chr4:26027183-26130530rs11933540T > C1.76e-04D1.10D
4q27chr4:122017479-122644147IL2  rs6827756C > T2.47e-06D1.13D
6p12.1chr6:56626042-57224910rs4236146G > T1.72e-05C1.16D
6p21.2chr6:38728915-38940535rs7749015A > G6.87e-06C1.19D
6q15chr6:90097116-90320436BACH2  rs597325G > A3.38e-10D1.18D
6q22.32chr6:126129075-127097155rs9375435C > T1.71e-06D1.13D
6q23.3chr6:137552553-137804198TNFAIP3  rs1878658A > G1.86e-04D1.14D
6q25.3chr6:158901294-159120449TAGAP  rs212402A > G2.11e-05D1.12D
6q27chr6:169879562-170130554rs924043C > T8.06e-09C1.19D
7p12.1chr7:50833794-51067601rs10231420A > G2.76e-06D1.25D
7p15.1chr7:28080094-28222707rs550448A > G4.68e-07C1.18D
7p15.2chr7:26780132-27185344SKAP2  rs12533947A > G7.08e-04D1.12D
7q21.3chr7:97553730-97772956rs2160774T > G1.00e-04C1.25D
8q24.12chr8:118763348-119111050TNFRSF11B  rs12679857A > G4.17e-07C1.14D
9p13.3chr9:34146778-34695472rs7857130C > G7.75e-05C1.12D
9p24.2chr9:4238265-4315442GLIS3  rs10758593G > A1.18e-08D1.15D
10p15.1chr10:5988280-6134149IL2RA  rs7090530A > C2.93e-15D1.22D
10p15.1chr10:6386901-6503142PRKCQ  rs2236380G > A1.87e-06D1.14D
10q22.1chr10:70553223-70722162rs10999432T > G3.26e-05C1.12D
10q23.31chr10:88245291-88476640rs10509540T > C2.83e-06D1.14D
10q24.2chr10:98482169-98606252rs10786436C > T8.08e-07C1.14D
10q25.2chr10:110845838-111105585rs11195417C > A7.55e-05C1.18D
11p15.1chr11:18197131-18256551rs2468844T > C3.21e-05C1.32D
11p15.5chr11:2026410-2051274INS  rs7928968A > T2.78e-14D1.25D
11q13.3chr11:69729740-69829387rs4084127G > A2.63e-06C1.14D
11q14.2chr11:86393416-86715724rs7935611G > T1.92e-05C1.38D
11q25chr11:133227716-133343124rs2212517T > C9.06e-05C1.25D
12p13.31chr12:9366576-9820167rs10492166G > A6.00e-09D1.15D
12q13.2chr12:55958153-56397446rs705704G > A4.31e-31D1.35D
12q14.1chr12:57586166-58101574CYP27B1  rs4760341T > A5.82e-04D1.1D
12q21.33chr12:89547772-90175928rs11105447G > C2.36e-05C1.20D
12q24.12chr12:111278572-112592683SH2B3  rs3184504T > C1.77e-21D1.27D
13q22.2chr13:75633429-75930423LMO7  rs539514T > A5.66e-11C1.14D
13q32.3chr13:99128207-99456553GPR183  rs6491500A > G1.44e-05D1.11D
14q11.2chr14:23289947-23409050rs10137082C > T5.96e-06C1.15D
14q24.1chr14:68696393-68851345rs927292G > C6.78e-07D1.15D
14q32.2chr14:98955388-99011415rs17098179T > C2.21e-05C1.14D
14q32.2chr14:97873990-98035540rs2616767A > G1.73e-03D1.09D
14q32.2chr14:100817324-100862402DLK1  rs941576A > G9.33e-05D1.1D
15q14chr15:38524632-38701912RASGRP1  rs12908309G > A4.31e-08D1.18D
15q25.1chr15:78709357-78968794rs12148472T > C2.37e-06D1.2D
16p11.2chr16:28283985-29014657IL27  rs9924471G > A1.21e-11D1.24D
16p13.13chr16:10923201-11220282rs12927355C > T1.91e-16D1.25D
16q23.1chr16:75182342-75487132rs8056814G > A1.13e-07D1.25D
17q12chr17:39226421-40083963ORMDL3  rs12150079G > A3.98e-04D1.10D
17q21.2chr17:40561644-40722575rs1358174A > G1.67e-04D1.1D
18p11.21chr18:12738414-12925254PTPN2  rs1893217A > G1.63e-08D1.20D
18q22.2chr18:69825789-69902311CD226  rs1790575T > C9.98e-05D1.10D
19p13.2chr19:10301842-10523588TYK2  rs1051738C > A1.34e-05D1.15D
19q13.32chr19:46648121-46820083rs4804000G > A6.31e-08D1.19D
19q13.33chr19:48592641-48763133rs602662A > G4.23e-05C1.12D
20p13chr20:1627564-1776075rs202536G > C1.11e-06D1.14D
21q22.3chr21:45216339-45329803rs2838873C > T1.22e-05C1.14D
21q22.3chr21:42389309-42458550UBASH3A  rs11203203G > A1.44e-07D1.14D
22q12.2chr22:29651931-30271212rs2412970A > G3.76e-04D1.1D
22q12.3chr22:37170990-37261499IL2RB  rs229526G > C8.33e-08D1.17D
MHCchr6:32372120-32697982rs6916742C > T4.56e-307D4.17D

Criteria

GDXHsS00001 meets the following criteria:

Criteria Name
Details
Disease Tags
Study for a Disease 

Publications

PMIDTitleFirst AuthorJournalDisease(s)Date