Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes
Patrick Concannon and colleagues present a type 1 diabetes genome-wide association study and meta-analysis in 7,514 cases and 9,045 reference samples, reporting 22 newly identified loci. Type 1 diabetes (T1D) is a common autoimmune disorder that arises from the action of multiple genetic and environ...
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| Veröffentlicht in: | Nature genetics 2009-06, Vol.41 (6), p.703-707 |
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| creator | Barrett, Jeffrey C Clayton, David G Concannon, Patrick Akolkar, Beena Cooper, Jason D Erlich, Henry A Julier, Cécile Morahan, Grant Nerup, Jørn Nierras, Concepcion Plagnol, Vincent Pociot, Flemming Schuilenburg, Helen Smyth, Deborah J Stevens, Helen Todd, John A Walker, Neil M Rich, Stephen S |
| description | Patrick Concannon and colleagues present a type 1 diabetes genome-wide association study and meta-analysis in 7,514 cases and 9,045 reference samples, reporting 22 newly identified loci.
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
. |
| doi_str_mv | 10.1038/ng.381 |
| format | Article |
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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
.</description><identifier>ISSN: 1061-4036</identifier><identifier>ISSN: 1546-1718</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/ng.381</identifier><identifier>PMID: 19430480</identifier><identifier>CODEN: NGENEC</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Agriculture ; Algorithms ; Animal Genetics and Genomics ; Antigens, CD - genetics ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Chromosome Mapping - methods ; Chromosomes, Human, Pair 1 - genetics ; Chromosomes, Human, Pair 17 - genetics ; Chromosomes, Human, Pair 2 - genetics ; Colleges & universities ; CTLA-4 Antigen ; DEAD-box RNA Helicases - genetics ; Diabetes ; Diabetes Mellitus, Type 1 - epidemiology ; Diabetes Mellitus, Type 1 - genetics ; Diabetes Mellitus, Type 1 - immunology ; Diabetes. Impaired glucose tolerance ; DNA - genetics ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Environmental risk ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Family ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Function ; Genetic aspects ; Genetic testing ; Genetics of eukaryotes. Biological and molecular evolution ; Genome-Wide Association Study ; Genomics ; Genotype ; HLA Antigens - genetics ; Human Genetics ; Humans ; Interferon-Induced Helicase, IFIH1 ; letter ; Male ; Medical sciences ; Mental health ; Meta-analysis ; Meta-Analysis as Topic ; Polymorphism, Single Nucleotide - genetics ; Principal components analysis ; Protein Tyrosine Phosphatase, Non-Receptor Type 22 - genetics ; Quality control ; Risk Assessment ; Risk factors ; Siblings ; Single nucleotide polymorphisms ; Studies ; Type 1 diabetes</subject><ispartof>Nature genetics, 2009-06, Vol.41 (6), p.703-707</ispartof><rights>Springer Nature America, Inc. 2009</rights><rights>2009 INIST-CNRS</rights><rights>COPYRIGHT 2009 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jun 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c603t-8a3d4def93a7e5ef1936e6eb8a2f6293e1ecbd2c268aaff120f8a3c2f59c455b3</citedby><cites>FETCH-LOGICAL-c603t-8a3d4def93a7e5ef1936e6eb8a2f6293e1ecbd2c268aaff120f8a3c2f59c455b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ng.381$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ng.381$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,550,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21543381$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19430480$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:118831967$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Barrett, Jeffrey C</creatorcontrib><creatorcontrib>Clayton, David G</creatorcontrib><creatorcontrib>Concannon, Patrick</creatorcontrib><creatorcontrib>Akolkar, Beena</creatorcontrib><creatorcontrib>Cooper, Jason D</creatorcontrib><creatorcontrib>Erlich, Henry A</creatorcontrib><creatorcontrib>Julier, Cécile</creatorcontrib><creatorcontrib>Morahan, Grant</creatorcontrib><creatorcontrib>Nerup, Jørn</creatorcontrib><creatorcontrib>Nierras, Concepcion</creatorcontrib><creatorcontrib>Plagnol, Vincent</creatorcontrib><creatorcontrib>Pociot, Flemming</creatorcontrib><creatorcontrib>Schuilenburg, Helen</creatorcontrib><creatorcontrib>Smyth, Deborah J</creatorcontrib><creatorcontrib>Stevens, Helen</creatorcontrib><creatorcontrib>Todd, John A</creatorcontrib><creatorcontrib>Walker, Neil M</creatorcontrib><creatorcontrib>Rich, Stephen S</creatorcontrib><creatorcontrib>Type 1 Diabetes Genetics Consortium</creatorcontrib><creatorcontrib>The Type 1 Diabetes Genetics Consortium</creatorcontrib><title>Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><addtitle>Nat Genet</addtitle><description>Patrick Concannon and colleagues present a type 1 diabetes genome-wide association study and meta-analysis in 7,514 cases and 9,045 reference samples, reporting 22 newly identified loci.
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
.</description><subject>Agriculture</subject><subject>Algorithms</subject><subject>Animal Genetics and Genomics</subject><subject>Antigens, CD - genetics</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Chromosome Mapping - methods</subject><subject>Chromosomes, Human, Pair 1 - genetics</subject><subject>Chromosomes, Human, Pair 17 - genetics</subject><subject>Chromosomes, Human, Pair 2 - genetics</subject><subject>Colleges & universities</subject><subject>CTLA-4 Antigen</subject><subject>DEAD-box RNA Helicases - genetics</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 1 - epidemiology</subject><subject>Diabetes Mellitus, Type 1 - genetics</subject><subject>Diabetes Mellitus, Type 1 - immunology</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>DNA - genetics</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Environmental risk</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Family</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Function</subject><subject>Genetic aspects</subject><subject>Genetic testing</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Genome-Wide Association Study</subject><subject>Genomics</subject><subject>Genotype</subject><subject>HLA Antigens - genetics</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Interferon-Induced Helicase, IFIH1</subject><subject>letter</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mental health</subject><subject>Meta-analysis</subject><subject>Meta-Analysis as Topic</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Principal components analysis</subject><subject>Protein Tyrosine Phosphatase, Non-Receptor Type 22 - genetics</subject><subject>Quality control</subject><subject>Risk Assessment</subject><subject>Risk factors</subject><subject>Siblings</subject><subject>Single nucleotide polymorphisms</subject><subject>Studies</subject><subject>Type 1 diabetes</subject><issn>1061-4036</issn><issn>1546-1718</issn><issn>1546-1718</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><sourceid>D8T</sourceid><recordid>eNqNkltrFTEQxxdRbK36ESQoKj5szWU3m30sRWuhUPD2Gmazk2Pa3c0xyVrPtzeHs7ScIiJ5yDD5zX8yl6J4zugxo0K9n1bHQrEHxSGrK1myhqmH2aaSlRUV8qB4EuMVpayqqHpcHLC2ErRS9LDAM5z8iOWN65FAjN44SM5PJKa53xCYejJighImGDbRRWJddqUfkIj_hYFUlAw5hoC1aBIJLl4Tb0narJEw0jvoMGF8WjyyMER8ttxHxbePH76efiovLs_OT08uSiOpSKUC0Vc92lZAgzVa1gqJEjsF3EreCmRoup4bLhXkhIxTm0MMt3VrqrruxFFR7nTjDa7nTq-DGyFstAenF9d1tlDXteKUZf7tjl8H_3PGmPToosFhgAn9HHVT10xySdtMvvknyalqZCOaDL68B175OeTuZYZzmYdUb_O-2kErGFC7yfoUwGwV9Un-F1VSNlup479Q-fQ4OuMntC779wLe7QVkJuHvtII5Rn3-5fP_s5ff99mleBN8jAHtbWMZ1dv109NK58oy-GIpfu5G7O-wZd8y8HoBIBoYbIDJuHjL8by9Yie0DCbmp2mF4a6L91L-AbST61U</recordid><startdate>20090601</startdate><enddate>20090601</enddate><creator>Barrett, Jeffrey C</creator><creator>Clayton, David G</creator><creator>Concannon, Patrick</creator><creator>Akolkar, Beena</creator><creator>Cooper, Jason D</creator><creator>Erlich, Henry A</creator><creator>Julier, Cécile</creator><creator>Morahan, Grant</creator><creator>Nerup, Jørn</creator><creator>Nierras, Concepcion</creator><creator>Plagnol, Vincent</creator><creator>Pociot, Flemming</creator><creator>Schuilenburg, Helen</creator><creator>Smyth, Deborah J</creator><creator>Stevens, Helen</creator><creator>Todd, John A</creator><creator>Walker, Neil M</creator><creator>Rich, Stephen S</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7T5</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20090601</creationdate><title>Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes</title><author>Barrett, Jeffrey C ; Clayton, David G ; Concannon, Patrick ; Akolkar, Beena ; Cooper, Jason D ; Erlich, Henry A ; Julier, Cécile ; Morahan, Grant ; Nerup, Jørn ; Nierras, Concepcion ; Plagnol, Vincent ; Pociot, Flemming ; Schuilenburg, Helen ; Smyth, Deborah J ; Stevens, Helen ; Todd, John A ; Walker, Neil M ; Rich, Stephen S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c603t-8a3d4def93a7e5ef1936e6eb8a2f6293e1ecbd2c268aaff120f8a3c2f59c455b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Agriculture</topic><topic>Algorithms</topic><topic>Animal Genetics and Genomics</topic><topic>Antigens, CD - genetics</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Chromosome Mapping - methods</topic><topic>Chromosomes, Human, Pair 1 - genetics</topic><topic>Chromosomes, Human, Pair 17 - genetics</topic><topic>Chromosomes, Human, Pair 2 - genetics</topic><topic>Colleges & universities</topic><topic>CTLA-4 Antigen</topic><topic>DEAD-box RNA Helicases - genetics</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 1 - epidemiology</topic><topic>Diabetes Mellitus, Type 1 - genetics</topic><topic>Diabetes Mellitus, Type 1 - immunology</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>DNA - genetics</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Environmental risk</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Family</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Function</topic><topic>Genetic aspects</topic><topic>Genetic testing</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Genome-Wide Association Study</topic><topic>Genomics</topic><topic>Genotype</topic><topic>HLA Antigens - genetics</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Interferon-Induced Helicase, IFIH1</topic><topic>letter</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mental health</topic><topic>Meta-analysis</topic><topic>Meta-Analysis as Topic</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Principal components analysis</topic><topic>Protein Tyrosine Phosphatase, Non-Receptor Type 22 - genetics</topic><topic>Quality control</topic><topic>Risk Assessment</topic><topic>Risk factors</topic><topic>Siblings</topic><topic>Single nucleotide polymorphisms</topic><topic>Studies</topic><topic>Type 1 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Barrett, Jeffrey C</creatorcontrib><creatorcontrib>Clayton, David 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Beena</au><au>Cooper, Jason D</au><au>Erlich, Henry A</au><au>Julier, Cécile</au><au>Morahan, Grant</au><au>Nerup, Jørn</au><au>Nierras, Concepcion</au><au>Plagnol, Vincent</au><au>Pociot, Flemming</au><au>Schuilenburg, Helen</au><au>Smyth, Deborah J</au><au>Stevens, Helen</au><au>Todd, John A</au><au>Walker, Neil M</au><au>Rich, Stephen S</au><aucorp>Type 1 Diabetes Genetics Consortium</aucorp><aucorp>The Type 1 Diabetes Genetics Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes</atitle><jtitle>Nature genetics</jtitle><stitle>Nat Genet</stitle><addtitle>Nat Genet</addtitle><date>2009-06-01</date><risdate>2009</risdate><volume>41</volume><issue>6</issue><spage>703</spage><epage>707</epage><pages>703-707</pages><issn>1061-4036</issn><issn>1546-1718</issn><eissn>1546-1718</eissn><coden>NGENEC</coden><abstract>Patrick Concannon and colleagues present a type 1 diabetes genome-wide association study and meta-analysis in 7,514 cases and 9,045 reference samples, reporting 22 newly identified loci.
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
.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>19430480</pmid><doi>10.1038/ng.381</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1061-4036 |
| ispartof | Nature genetics, 2009-06, Vol.41 (6), p.703-707 |
| issn | 1061-4036 1546-1718 1546-1718 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_558201 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online; SWEPUB Freely available online |
| subjects | Agriculture Algorithms Animal Genetics and Genomics Antigens, CD - genetics Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Research Chromosome Mapping - methods Chromosomes, Human, Pair 1 - genetics Chromosomes, Human, Pair 17 - genetics Chromosomes, Human, Pair 2 - genetics Colleges & universities CTLA-4 Antigen DEAD-box RNA Helicases - genetics Diabetes Diabetes Mellitus, Type 1 - epidemiology Diabetes Mellitus, Type 1 - genetics Diabetes Mellitus, Type 1 - immunology Diabetes. Impaired glucose tolerance DNA - genetics Endocrine pancreas. Apud cells (diseases) Endocrinopathies Environmental risk Etiopathogenesis. Screening. Investigations. Target tissue resistance Family Female Fundamental and applied biological sciences. Psychology Gene Function Genetic aspects Genetic testing Genetics of eukaryotes. Biological and molecular evolution Genome-Wide Association Study Genomics Genotype HLA Antigens - genetics Human Genetics Humans Interferon-Induced Helicase, IFIH1 letter Male Medical sciences Mental health Meta-analysis Meta-Analysis as Topic Polymorphism, Single Nucleotide - genetics Principal components analysis Protein Tyrosine Phosphatase, Non-Receptor Type 22 - genetics Quality control Risk Assessment Risk factors Siblings Single nucleotide polymorphisms Studies Type 1 diabetes |
| title | Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T17%3A07%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genome-wide%20association%20study%20and%20meta-analysis%20find%20that%20over%2040%20loci%20affect%20risk%20of%20type%201%20diabetes&rft.jtitle=Nature%20genetics&rft.au=Barrett,%20Jeffrey%20C&rft.aucorp=Type%201%20Diabetes%20Genetics%20Consortium&rft.date=2009-06-01&rft.volume=41&rft.issue=6&rft.spage=703&rft.epage=707&rft.pages=703-707&rft.issn=1061-4036&rft.eissn=1546-1718&rft.coden=NGENEC&rft_id=info:doi/10.1038/ng.381&rft_dat=%3Cgale_swepu%3EA201086677%3C/gale_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=222638151&rft_id=info:pmid/19430480&rft_galeid=A201086677&rfr_iscdi=true |