Follow-Up Analysis of Genome-Wide Association Data Identifies Novel Loci for Type 1 Diabetes

被引：122

作者：

Grant, Struan F. A. ^{[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
]}

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
]}

Skraban, Robert ^{[1
]}

Imielinski, Marcin ^{[1
]}

Chiavacci, Rosetta M. ^{[1
]}

Grundmeier, Robert W. ^{[8
,9
]}

Stanley, Charles A. ^{[10
]}

Kirsch, Susan E. ^{[11
]}

Waggott, Daryl ^{[12
]}

Paterson, Andrew D. ^{[13
]}

Monos, Dimitri S. ^{[3
,14
]}

Polychronakos, Constantin ^{[4
,5
]}

Hakonarson, Hakon ^{[1
,2
]}

机构：

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

[2] Childrens Hosp Philadelphia, Abramson Res Ctr, Div Human Genet, Philadelphia, PA 19104 USA

[3] Univ Penn, Sch Med, Dept Pediat, 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] Childrens Hosp Philadelphia, Abramson Res Ctr, Pediat Res Consortium, Philadelphia, PA 19104 USA

[9] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA

[10] Childrens Hosp Philadelphia, Abramson Res Ctr, Div Endocrinol, Philadelphia, PA 19104 USA

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

[12] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada

[13] Univ Toronto, Dept Publ Hlth Sci, Hosp Sick Kids, Toronto, ON, Canada

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

来源：

DIABETES | 2009年 / 58卷 / 01期

基金：

美国国家卫生研究院; 加拿大健康研究院;

关键词：

SUSCEPTIBILITY; REGION;

D O I：

10.2337/db08-1022

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

OBJECTIVE-Two recent genome-wide association (GWA) studies have revealed novel loci for type 1 diabetes, a common multifactorial disease with a strong genetic component. To fully utilize the GWA data that we had obtained by genotyping 563 type 1 diabetes probands and 1,146 control subjects, as well as 483 case subject-parent trios, using the Illumina HumanHap550 BeadChip, we designed a full stage 2 study to capture other possible association signals. RESEARCH DESIGN AND METHODS-From our existing datasets, we selected 982 markers with P < 0.05 in both GWA cohorts. Genotyping these in an independent set of 636 nuclear families with 974 affected offspring revealed 75 markers that also had P < 0.05 in this third cohort. Among these, six single nucleotide polymorphisms in five novel loci also had P < 0.05 in the Wellcome Trust Case-Control Consortium dataset and were further tested in 1,303 type 1 diabetes probands from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) plus 1,673 control subjects. RESULTS-Two markers (rs9976767 and rs3757247) remained significant after adjusting for the number of tests in this last cohort; they reside in UBASH3A (OR 1.16; combined P = 2.33 X 10(-8)) and BACH2 (1.13; combined P = 1.25 X 10(-6)). CONCLUSIONS-Evaluation of a large number of statistical GWA candidates in several independent cohorts has revealed additional loci that are associated with type 1 diabetes. The two genes at these respective loci, UBASH3A and BACH2, are both biologically relevant to autoimmunity. Diabetes 58:290-295, 2009

引用

页码：290 / 295

页数：6

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