Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes.
- Todd, JA
- Walker, NM
- Cooper, JD
- Smyth, DJ
- Downes, K
- Plagnol, V
- Bailey, R
- Nejentsev, S
- Field, SF
- Payne, F
- Lowe, CE
- Szeszko, JS
- Hafler, JP
- Zeitels, L
- Yang, JH
- Vella, A
- Nutland, S
- Stevens, HE
- Schuilenburg, H
- Coleman, G
- Maisuria, M
- Meadows, W
- Smink, LJ
- Healy, B
- Burren, OS
- Lam, AA
- Ovington, NR
- Allen, J
- Adlem, E
- Leung, HT
- Wallace, C
- Howson, JM
- Guja, C
- Ionescu-Tîrgovişte, C
- Simmonds, MJ
- Heward, JM
- Gough, SC
- Dunger, DB
- Wicker, LS
- Clayton, DG
DOIAbstract
The Wellcome Trust Case Control Consortium (WTCCC) primary genome-wide association (GWA) scan on seven diseases, including the multifactorial autoimmune disease type 1 diabetes (T1D), shows associations at P < 5 x 10(-7) between T1D and six chromosome regions: 12q24, 12q13, 16p13, 18p11, 12p13 and 4q27. Here, we attempted to validate these and six other top findings in 4,000 individuals with T1D, 5,000 controls and 2,997 family trios independent of the WTCCC study. We confirmed unequivocally the associations of 12q24, 12q13, 16p13 and 18p11 (P(follow-up) <or= 1.35 x 10(-9); P(overall) <or= 1.15 x 10(-14)), leaving eight regions with small effects or false-positive associations. We also obtained evidence for chromosome 18q22 (P(overall) = 1....
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