A novel susceptibility locus for type 1 diabetes on Chr12q13 identified by a genome-wide association study

被引：115

作者：

Hakonarson, Hakon ^{[1
,2
,3
]}

Qu, Hui-Qi ^{[4
,5
]}

Bradfield, Jonathan P. ^{[1
]}

Marchand, Luc ^{[4
,5
]}

Kim, Cecilia E. ^{[1
]}

Glessner, Joseph T. ^{[1
]}

Grabs, Rosemarie ^{[4
,5
]}

Casalunovo, Tracy ^{[1
]}

Taback, Shayne P. ^{[6
]}

Frackelton, Edward C. ^{[1
]}

Eckert, Andrew W. ^{[1
]}

Annaiah, Kiran ^{[1
]}

Lawson, Margaret L. ^{[7
]}

Otieno, F. George ^{[1
]}

Santa, Erin ^{[1
]}

Shaner, Julie L. ^{[1
]}

Smith, Ryan M. ^{[1
]}

Onyiah, Chioma C. ^{[1
]}

Skraban, Robert ^{[1
]}

Chiavacci, Rosetta M. ^{[1
]}

Robinson, Luke J. ^{[1
]}

Stanley, Charles A. ^{[8
]}

Kirsch, Susan E. ^{[9
]}

Devoto, Marcella ^{[2
,3
,10
]}

Monos, Dimitri S. ^{[11
,12
]}

Grant, Struan F. A. ^{[1
,2
,3
]}

Polychronakos, Constantin ^{[4
,5
]}

机构：

[1] Univ Penn, Childrens Hosp Philadelphia, Abramson Res Ctr, Ctr Appl Genom, Philadelphia, PA 19104 USA

[2] Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA

[3] Univ Penn, Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA

[4] McGill Univ, Dept Pediat, Montreal, PQ H3A 2T5, Canada

[5] McGill Univ, Dept Human Genet, Montreal, PQ H3A 2T5, Canada

[6] Univ Manitoba, Dept Pediat & Child Hlth, Winnipeg, MB R3T 2N2, Canada

[7] Univ Ottawa, Childrens Hosp Eastern Ontario, Div Endocrinol, Ottawa, ON, Canada

[8] Univ Penn, Childrens Hosp Philadelphia, Div Endocrinol, Philadelphia, PA 19104 USA

[9] Markham Stouffville Hosp, Markham, ON, Canada

[10] Univ Penn, Dept Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA

[11] Univ Penn, Childrens Hosp Philadelphia, Abramson Res Ctr, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[12] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA

来源：

DIABETES | 2008年 / 57卷 / 04期

关键词：

D O I：

10.2337/db07-1305

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

OBJECTIVE-In stage 1 of our genome-wide association (GWA) study for type 1 diabetes, one locus at 16p13 was detected (P = 1.03 x 10(-10)) and confirmed in two additional cohorts. Here we describe the results of testing, in these additional cohorts, 23 loci that were next in rank of statistical significance. RESEARCH DESIGN AND METHODS-Two independent cohorts were studied. The Type 1 Diabetes Genetics Consortium replication cohort consisted of 549 families with at least one child diagnosed with diabetes (946 total affected) and DNA from both parents. The Canadian replication cohort consisted of 364 nuclear family trios with one type 1 diabetes-affected offspring and two parents (1,092 individuals). RESULTS-One locus at 12q13, with the highest statistical significance among the 23, was confirmed. It involves type 1 diabetes association with the minor allele of rs1701704 (P = 9.13 x 10(-10), OR 1.25 [95% CI 1.12-1.40]). CONCLUSIONS-We have discovered a type 1 diabetes locus at 12q13 that is replicated in an independent cohort of type 1 diabetic patients and confers a type I diabetes risk comparable with that of the 16p13 locus we recently reported. These two loci are identical to two loci identified by the whole-genome association study of the Wellcome Trust Case-Control Consortium, a parallel independent discovery that adds further support to the validity of the GWA approach.

引用

页码：1143 / 1146

页数：4

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