Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes

Jeffrey C Barrett; David G Clayton; Patrick Concannon; Beena Akolkar; Jason D Cooper; Henry A Erlich; Cécile Julier; Grant Morahan; Jørn Nerup; Concepcion Nierras; Vincent Plagnol; Flemming Pociot; Helen Schuilenburg; Deborah J Smyth; Helen Stevens; John A Todd; Neil M Walker; Stephen S Rich; Type 1 Diabetes Genetics Consortium (Jesper Johannesen, member)

doi:10.1038/ng.381

Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes

Jeffrey C Barrett
, David G Clayton
, Patrick Concannon
, Beena Akolkar
, Jason D Cooper
, Henry A Erlich
, Cécile Julier
, Grant Morahan
, Jørn Nerup
, Concepcion Nierras
, Vincent Plagnol
, Flemming Pociot
, Helen Schuilenburg
, Deborah J Smyth
, Helen Stevens
, John A Todd
, Neil M Walker
, Stephen S Rich
, Type 1 Diabetes Genetics Consortium (Jesper Johannesen, member)

1495 Citations (Scopus)

Abstract

Type 1 diabetes (T1D) is a common autoimmune disorder that arises from the action of multiple genetic and environmental risk factors. We report the findings of a genome-wide association study of T1D, combined in a meta-analysis with two previously published studies. The total sample set included 7,514 cases and 9,045 reference samples. Forty-one distinct genomic locations provided evidence for association with T1D in the meta-analysis (P < 10(-6)). After excluding previously reported associations, we further tested 27 regions in an independent set of 4,267 cases, 4,463 controls and 2,319 affected sib-pair (ASP) families. Of these, 18 regions were replicated (P < 0.01; overall P < 5 × 10(-8)) and 4 additional regions provided nominal evidence of replication (P < 0.05). The many new candidate genes suggested by these results include IL10, IL19, IL20, GLIS3, CD69 and IL27.

Original language	English
Journal	Nature Genetics
Volume	41
Issue number	6
Pages (from-to)	703-7
Number of pages	5
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.381
Publication status	Published - Jun 2009
Externally published	Yes

Keywords

Algorithms
Antigens, CD
CTLA-4 Antigen
Chromosome Mapping
Chromosomes, Human, Pair 1
Chromosomes, Human, Pair 17
Chromosomes, Human, Pair 2
DEAD-box RNA Helicases
DNA
Diabetes Mellitus, Type 1
Family
Female
Genome-Wide Association Study
Genotype
HLA Antigens
Humans
Male
Meta-Analysis as Topic
Polymorphism, Single Nucleotide
Protein Tyrosine Phosphatase, Non-Receptor Type 22
Risk Assessment
Siblings
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

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10.1038/ng.381

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Barrett, J. C., Clayton, D. G., Concannon, P., Akolkar, B., Cooper, J. D., Erlich, H. A., Julier, C., Morahan, G., Nerup, J., Nierras, C., Plagnol, V., Pociot, F., Schuilenburg, H., Smyth, D. J., Stevens, H., Todd, J. A., Walker, N. M., Rich, S. S., & Type 1 Diabetes Genetics Consortium (Jesper Johannesen, member) (2009). Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nature Genetics, 41(6), 703-7. https://doi.org/10.1038/ng.381

Barrett, JC, Clayton, DG, Concannon, P, Akolkar, B, Cooper, JD, Erlich, HA, Julier, C, Morahan, G, Nerup, J, Nierras, C, Plagnol, V, Pociot, F, Schuilenburg, H, Smyth, DJ, Stevens, H, Todd, JA, Walker, NM, Rich, SS & Type 1 Diabetes Genetics Consortium (Jesper Johannesen, member) 2009, 'Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes', Nature Genetics, vol. 41, no. 6, pp. 703-7. https://doi.org/10.1038/ng.381

@article{9121e928fc694e0a896ad78f09183329,

title = "Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes",

abstract = "Type 1 diabetes (T1D) is a common autoimmune disorder that arises from the action of multiple genetic and environmental risk factors. We report the findings of a genome-wide association study of T1D, combined in a meta-analysis with two previously published studies. The total sample set included 7,514 cases and 9,045 reference samples. Forty-one distinct genomic locations provided evidence for association with T1D in the meta-analysis (P < 10(-6)). After excluding previously reported associations, we further tested 27 regions in an independent set of 4,267 cases, 4,463 controls and 2,319 affected sib-pair (ASP) families. Of these, 18 regions were replicated (P < 0.01; overall P < 5 {\texttimes} 10(-8)) and 4 additional regions provided nominal evidence of replication (P < 0.05). The many new candidate genes suggested by these results include IL10, IL19, IL20, GLIS3, CD69 and IL27.",

keywords = "Algorithms, Antigens, CD, CTLA-4 Antigen, Chromosome Mapping, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 17, Chromosomes, Human, Pair 2, DEAD-box RNA Helicases, DNA, Diabetes Mellitus, Type 1, Family, Female, Genome-Wide Association Study, Genotype, HLA Antigens, Humans, Male, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Protein Tyrosine Phosphatase, Non-Receptor Type 22, Risk Assessment, Siblings, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",

author = "Barrett, \{Jeffrey C\} and Clayton, \{David G\} and Patrick Concannon and Beena Akolkar and Cooper, \{Jason D\} and Erlich, \{Henry A\} and C{\'e}cile Julier and Grant Morahan and J{\o}rn Nerup and Concepcion Nierras and Vincent Plagnol and Flemming Pociot and Helen Schuilenburg and Smyth, \{Deborah J\} and Helen Stevens and Todd, \{John A\} and Walker, \{Neil M\} and Rich, \{Stephen S\} and \{Type 1 Diabetes Genetics Consortium (Jesper Johannesen, member)\} and J Johannesen",

year = "2009",

month = jun,

doi = "10.1038/ng.381",

language = "English",

volume = "41",

pages = "703--7",

journal = "Nature Genetics",

issn = "1061-4036",

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T1 - Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes

AU - Barrett, Jeffrey C

AU - Clayton, David G

AU - Concannon, Patrick

AU - Akolkar, Beena

AU - Cooper, Jason D

AU - Erlich, Henry A

AU - Julier, Cécile

AU - Morahan, Grant

AU - Nerup, Jørn

AU - Nierras, Concepcion

AU - Plagnol, Vincent

AU - Pociot, Flemming

AU - Schuilenburg, Helen

AU - Smyth, Deborah J

AU - Stevens, Helen

AU - Todd, John A

AU - Walker, Neil M

AU - Rich, Stephen S

AU - Type 1 Diabetes Genetics Consortium (Jesper Johannesen, member)

A2 - Johannesen, J

PY - 2009/6

Y1 - 2009/6

N2 - Type 1 diabetes (T1D) is a common autoimmune disorder that arises from the action of multiple genetic and environmental risk factors. We report the findings of a genome-wide association study of T1D, combined in a meta-analysis with two previously published studies. The total sample set included 7,514 cases and 9,045 reference samples. Forty-one distinct genomic locations provided evidence for association with T1D in the meta-analysis (P < 10(-6)). After excluding previously reported associations, we further tested 27 regions in an independent set of 4,267 cases, 4,463 controls and 2,319 affected sib-pair (ASP) families. Of these, 18 regions were replicated (P < 0.01; overall P < 5 × 10(-8)) and 4 additional regions provided nominal evidence of replication (P < 0.05). The many new candidate genes suggested by these results include IL10, IL19, IL20, GLIS3, CD69 and IL27.

AB - Type 1 diabetes (T1D) is a common autoimmune disorder that arises from the action of multiple genetic and environmental risk factors. We report the findings of a genome-wide association study of T1D, combined in a meta-analysis with two previously published studies. The total sample set included 7,514 cases and 9,045 reference samples. Forty-one distinct genomic locations provided evidence for association with T1D in the meta-analysis (P < 10(-6)). After excluding previously reported associations, we further tested 27 regions in an independent set of 4,267 cases, 4,463 controls and 2,319 affected sib-pair (ASP) families. Of these, 18 regions were replicated (P < 0.01; overall P < 5 × 10(-8)) and 4 additional regions provided nominal evidence of replication (P < 0.05). The many new candidate genes suggested by these results include IL10, IL19, IL20, GLIS3, CD69 and IL27.

KW - Algorithms

KW - Antigens, CD

KW - CTLA-4 Antigen

KW - Chromosome Mapping

KW - Chromosomes, Human, Pair 1

KW - Chromosomes, Human, Pair 17

KW - Chromosomes, Human, Pair 2

KW - DEAD-box RNA Helicases

KW - DNA

KW - Diabetes Mellitus, Type 1

KW - Family

KW - Female

KW - Genome-Wide Association Study

KW - Genotype

KW - HLA Antigens

KW - Humans

KW - Male

KW - Meta-Analysis as Topic

KW - Polymorphism, Single Nucleotide

KW - Protein Tyrosine Phosphatase, Non-Receptor Type 22

KW - Risk Assessment

KW - Siblings

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/ng.381

DO - 10.1038/ng.381

M3 - Journal article

C2 - 19430480

SN - 1061-4036

VL - 41

SP - 703

EP - 707

JO - Nature Genetics

JF - Nature Genetics

IS - 6

ER -

Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes

Abstract

Keywords

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