Skip to main content
  • More from ADA
    • Diabetes Care
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care in Diabetes
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care
  • Subscribe
  • Log in
  • My Cart
  • Follow ada on Twitter
  • RSS
  • Visit ada on Facebook
Diabetes

Advanced Search

Main menu

  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • ADA Scientific Sessions Abstracts
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • ADA Scientific Sessions Abstracts
    • Diabetes COVID-19 Article Collection
    • Diabetes Symposium 2020
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Submit Cover Art
    • ADA Journal Policies
    • Instructions for Authors
    • ADA Peer Review
  • More from ADA
    • Diabetes Care
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care in Diabetes
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care

User menu

  • Subscribe
  • Log in
  • My Cart

Search

  • Advanced search
Diabetes
  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • ADA Scientific Sessions Abstracts
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • ADA Scientific Sessions Abstracts
    • Diabetes COVID-19 Article Collection
    • Diabetes Symposium 2020
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Submit Cover Art
    • ADA Journal Policies
    • Instructions for Authors
    • ADA Peer Review
Genetics

HLA Class I and Genetic Susceptibility to Type 1 Diabetes

Results From the Type 1 Diabetes Genetics Consortium

  1. Janelle A. Noble1,
  2. Ana Maria Valdes2,
  3. Michael D. Varney3,
  4. Joyce A. Carlson4,
  5. Priscilla Moonsamy5,
  6. Anna Lisa Fear1,
  7. Julie A. Lane1,
  8. Eva Lavant4,
  9. Rebecca Rappner4,
  10. Anthony Louey3,
  11. Patrick Concannon6,
  12. Josyf C. Mychaleckyj6,
  13. Henry A. Erlich1,5 and
  14. for the Type 1 Diabetes Genetics Consortium
  1. 1Children's Hospital Oakland Research Institute, Oakland, California;
  2. 2Department of Twin Research and Genetic Epidemiology, King's College London, London, U.K.;
  3. 3Victorian Transplantation and Immunogenetics Service, Australian Red Cross Blood Service, Melbourne, Australia;
  4. 4Clinical Chemistry, University Hospital, Malmö, Sweden;
  5. 5Roche Molecular Systems, Pleasanton, California;
  6. 6Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia.
  1. Corresponding author: Janelle A. Noble, jnoble{at}chori.org.
Diabetes 2010 Nov; 59(11): 2972-2979. https://doi.org/10.2337/db10-0699
PreviousNext
  • Article
  • Figures & Tables
  • Suppl Material
  • Info & Metrics
  • PDF
Loading

Article Figures & Tables

Figures

  • Tables
  • FIG. 1.
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIG. 1.

    LD diagram for selected HLA alleles. The r2 × 100 value of LD between pairs of alleles is shown.

Tables

  • Figures
  • TABLE 1

    Descriptive statistics of sample studied

    CohortOriginCollectionPedigreesType 1 diabetic sibs per pedigreeType 1 diabetic offspring in cohortType 1 diabetic maleType 1 diabetic femaleMale (%)Age of onset (years)Age of onset (range)
    APAsia PacificNew1502.02 ± 0.2430315315050.5010.06 ± 7.430–37
    DANDenmarkExtant942.05 ± 0.331941059054.1211.73 ± 8.300.8–49
    EUREuropeNew4702.01 ± 0.1094551343254.2910.76 ± 7.261–35
    HBDIU.S.Extant4162.10 ± 0.4287947141053.5811.90 ± 8.220.8–50
    JOSU.S.Extant572.14 ± 0.58122606249.1811.22 ± 7.311–31
    NAU.S.New4072.01 ± 0.2181943538453.118.763 ± 6.450–34
    SARSardiniaExtant521.98 ± 0.14101475446.5312.34 ± 7.900.7–34
    UKU.K.New1072.00 ± 0.132149711745.337.65 ± 4.480–23
    Total1,7532.03 ± 0.283,5771,8811,69952.5910.44 ± 7.410–50
    • Data are means ± SD unless otherwise indicated.

  • TABLE 2

    HLA class I allele frequencies in 3,506 chromosomes from 1,753 type 1 diabetic probands and 1,585 affected family-based control chromosomes

    AlleleType 1 diabetes (n)AFBAC (n)P
    A*010117.7 (621)16.1 (256)0.214
    A*01020.1 (4)0 (0)0.179
    A*01030 (0)0.1 (2)0.035
    A*020130.6 (1,074)27.6 (438)0.069
    A*02020.2 (8)0 (0)0.057
    A*02052.1 (73)1.2 (19)0.030
    A*02060.3 (9)0.2 (3)0.646
    A*02110 (1)0 (0)0.501
    A*02200 (0)0.1 (1)0.137
    A*02340 (0)0.1 (1)0.137
    A*02350 (0)0.1 (1)0.137
    A*030111.9 (417)13.1 (207)0.271
    A*03020.5 (16)0.3 (4)0.282
    A*03050 (0)0.1 (1)0.137
    A*11013.4 (119)6.9 (109)5.E-08
    A*11050 (0)0.1 (1)0.137
    A*23011.2 (43)1.8 (29)0.094
    A*24010 (0)0.1 (1)0.137
    A*240211.3 (396)7.8 (123)2.E-04
    A*24030.3 (10)0.1 (1)0.114
    A*25012.3 (80)2.6 (42)0.432
    A*26012.6 (90)2.8 (44)0.671
    A*26070 (0)0.1 (1)0.137
    A*26080.1 (2)0 (0)0.342
    A*29010.3 (12)0.4 (6)0.840
    A*29022.3 (80)3.4 (54)0.022
    A*30010.7 (25)1.1 (17)0.191
    A*30023.3 (117)1.7 (27)0.001
    A*30040.1 (2)0.1 (1)0.934
    A*30100 (1)0 (0)0.501
    A*31012.1 (74)1.9 (30)0.614
    A*32012.1 (73)4.2 (67)2.E-05
    A*32040 (0)0.1 (1)0.137
    A*33010.8 (27)1 (16)0.390
    A*33030.4 (14)0.3 (5)0.650
    A*34020.2 (6)0.1 (1)0.336
    A*36010 (1)0.1 (2)0.184
    A*66010.1 (3)0.6 (10)4.E-04
    A*66020.1 (2)0 (0)0.342
    A*68012.6 (91)2.7 (43)0.811
    A*68020.4 (14)1.3 (20)5.E-04
    A*69010 (0)0.1 (1)0.137
    A*74010 (0)0.1 (1)0.137
    A*80010 (1)0 (0)0.501
    B*07027 (244)14.7 (233)7.E-17
    B*07040 (0)0.1 (1)0.137
    B*07050.7 (26)0.3 (4)0.035
    B*07070 (0)0.1 (1)0.137
    B*080121 (735)10.9 (173)4.E-15
    B*08090 (0)0.1 (1)0.137
    B*13021.8 (64)2 (31)0.752
    B*14010.2 (8)0.6 (9)0.052
    B*14021.7 (60)2.6 (41)0.040
    B*150112.3 (432)4.5 (71)2.E-16
    B*15020.1 (2)0 (0)0.342
    B*15030.1 (5)0.1 (1)0.444
    B*15070.1 (3)0 (0)0.244
    B*15080 (1)0 (0)0.501
    B*15090.1 (2)0.1 (1)0.934
    B*15100.1 (4)0 (0)0.179
    B*15150 (1)0 (0)0.501
    B*15160 (1)0.1 (1)0.564
    B*15170.4 (15)0.3 (4)0.343
    B*15180.2 (6)0.3 (5)0.305
    B*15240.1 (3)0 (0)0.244
    B*15250 (0)0.1 (1)0.137
    B*15370 (1)0 (0)0.501
    B*15710 (0)0.1 (1)0.137
    B*15730 (0)0.1 (1)0.137
    B*180110.2 (357)6.3 (100)2.E-05
    B*18120 (1)0 (0)0.501
    B*27010 (0)0.1 (1)0.137
    B*27020.3 (9)0.4 (6)0.458
    B*27033.2 (113)3.1 (49)0.807
    B*27070 (1)0.1 (2)0.184
    B*35013.6 (126)6.3 (100)2.E-05
    B*35020.3 (12)1.5 (23)1.E-05
    B*35031.6 (56)1.5 (23)0.698
    B*35080.3 (12)0.5 (8)0.392
    B*35120 (0)0.1 (1)0.137
    B*37010.7 (23)1 (16)0.182
    B*38011.8 (63)2.5 (40)0.091
    B*39011.2 (42)1.2 (19)0.998
    B*39063.2 (112)0.4 (7)3.E-09
    B*40015.6 (198)4.4 (69)0.062
    B*40020.6 (20)1.6 (25)4.E-04
    B*40060.1 (3)0.2 (3)0.318
    B*40090 (1)0 (0)0.501
    B*40140 (0)0.1 (2)0.035
    B*41011 (34)0.3 (4)0.006
    B*41020.1 (2)0.4 (6)0.007
    B*42010 (1)0 (0)0.501
    B*42020 (0)0.1 (1)0.137
    B*44026 (210)9 (143)1.E-04
    B*44032 (69)5.7 (91)2.E-12
    B*44040 (0)0.1 (1)0.137
    B*44050.2 (7)0.1 (1)0.255
    B*45010.5 (17)0.4 (7)0.835
    B*47010.3 (10)0.4 (6)0.582
    B*47020 (1)0 (0)0.501
    B*48010.1 (2)0.1 (1)0.934
    B*49012.2 (77)1.1 (17)0.006
    B*50012.1 (75)1.2 (19)0.022
    B*50020.1 (2)0.1 (1)0.934
    B*51013 (104)4.2 (67)0.023
    B*51020 (0)0.1 (1)0.137
    B*51050 (0)0.1 (1)0.137
    B*51070 (1)0.1 (1)0.564
    B*51080.1 (4)0.1 (1)0.591
    B*52010.3 (12)1.1 (18)0.001
    B*53010.1 (5)0.5 (8)0.018
    B*55010.9 (30)1.6 (26)0.013
    B*56010.6 (20)0.6 (10)0.795
    B*57010.5 (19)3.5 (56)4.E-16
    B*57030 (1)0.3 (5)0.006
    B*58010.9 (31)1.1 (18)0.397
    B*73010.3 (9)0.1 (1)0.149
    B*81010 (1)0 (0)0.501
    C*01022 (69)3 (48)0.021
    C*02023.9 (136)4.4 (69)0.435
    C*02060 (1)0.1 (1)0.564
    C*03020.3 (12)0.4 (7)0.591
    C*03035.5 (194)3.9 (62)0.017
    C*030413.5 (475)6.6 (105)1.E-11
    C*03050.1 (3)0 (0)0.244
    C*03140 (1)0 (0)0.501
    C*04016 (212)11.6 (184)4.E-11
    C*04030 (0)0.1 (1)0.137
    C*050111.3 (397)9.5 (150)0.061
    C*06025.9 (208)8.4 (133)0.002
    C*06060 (1)0 (0)0.501
    C*070125.7 (900)15 (238)1.E-13
    C*070210.8 (378)15.6 (247)6.E-06
    C*07041 (34)1.9 (30)0.007
    C*08010.1 (5)0.1 (2)0.884
    C*08021.9 (66)3.2 (50)0.005
    C*12020.3 (12)1.1 (17)0.001
    C*12035.7 (200)6.4 (102)0.322
    C*14020.7 (25)1.2 (19)0.084
    C*15021.4 (50)2 (32)0.123
    C*15040.2 (8)0.1 (2)0.447
    C*15050.8 (27)0.3 (5)0.058
    C*16011.2 (43)3.8 (60)3.E-09
    C*16020.5 (17)0.2 (3)0.119
    C*16040.1 (4)0.4 (6)0.049
    C*17010.8 (27)0.7 (11)0.771
    C*18010 (1)0.1 (1)0.564
    • P values lower than 0.1 are shown in boldface type.

  • TABLE 3

    HLA class I alleles significantly different from expected values when accounting for LD with DRB1-DQB1

    AlleleType 1 diabetes observed (%)Type 1 diabetes expected (%)†OR (95% CI)P
    A*010117.721.90.77 (0.66–0.88)0.002
    A*020130.624.71.35 (1.17–1.54)3.E-04
    A*11013.46.20.53 (0.40–0.70)8.E-06
    A*240211.47.01.71 (1.37–2.12)5.E-06
    A*32012.13.80.54 (0.37–0.75)4.E-04
    A*66010.10.60.16 (0.04–0.57)9.E-04
    A*68020.41.20.34 (0.17–0.69)0.002
    B*07027.011.40.58 (0.47–0.70)3.E-07
    B*07050.70.23.42 (1.11–10.5)0.023
    B*150112.39.41.36 (1.11–1.65)0.004
    B*180110.25.22.05 (1.59–2.61)3.E-08
    B*35013.64.90.72 (0.53–0.96)0.028
    B*35020.31.20.29 (0.14–0.60)5.E-04
    B*39063.20.310.31 (4.21–25.1)4.E-10
    B*40020.51.20.45 (0.23–0.84)0.012
    B*41011.00.24.49 (1.48–13.6)0.004
    B*41020.10.30.19 (0.03–0.96)0.020
    B*44031.94.50.42 (0.30–0.59)4.E-07
    B*49012.20.92.6 (1.45–4.63)0.001
    B*50012.11.02.27 (1.30–3.94)0.003
    B*52010.30.90.37 (0.17–0.80)0.009
    B*53010.10.40.33 (0.10–1.06)0.055
    B*57010.52.80.19 (0.11–0.32)4.E-11
    B*57030.00.30.11 (0.01–0.96)0.013
    C*03035.53.81.48 (1.10–1.99)0.010
    C*04016.09.30.63 (0.50–0.78)6.E-05
    C*050111.37.61.56 (1.26–1.93)9.E-05
    C*12020.30.90.39 (0.17–0.83)0.014
    C*14020.71.40.52 (0.29–0.93)0.027
    C*15050.80.32.78 (1.01–7.62)0.039
    C*16011.23.00.39 (0.25–0.58)5.E-06
    • †Expected values calculated based on LD of class I alleles with DR-DQ–encoding loci in this population.

  • TABLE 4

    Protective effect of C*1601 appears to be caused by LD with B*4403

    DRHLA-BHLA-CNot transTransTrans proportion (%)P
    AllB*4403All28211829.50
    AllB*4403C*16011566629.73
    AllB*4403not C*16011154025.81NS
    AllAllC*16011738031.62
    AllB*4403C*16011566629.73
    Allnot B*4403C*1601171445.16<0.13
    DR7†B*4403not C*1601811010.99
    DR7not B*4403C*16013457.14<0.0074
    DR7B*4403C*16011243622.50
    DR7B*4403not C*1601811010.99<0.023
    DR7B*4403C*16011243622.50
    DR7not B*4403C*16013457.14<0.036
    • †DRB1*0701 DQB1*0201.

  • TABLE 5

    Summary of statistically significant relative ORs on specific haplotypes for class I alleles

    AlleleDR3DR4DR8DR1DR2NumberConsistent effect
    A*01010.69 (0.59–0.78)0.75 (0.57–0.98)2Yes
    A*02010.58 (0.38–0.89)
    A*03011.47 (1.14–1.88)
    A*1101X0.60 (0.38–0.91)
    A*24021.69 (1.25–2.28)1.52 (1.15–2.01)3.31 (1.90–5.74)2.18 (1.51–3.14)4Yes
    A*26010.65 (0.46–0.89)X
    A*29022.22 (1.03–4.78)
    A*31010.57 (0.41–0.79)
    A*32010.57 (0.36–0.88)0.19 (0.04–0.89)X2Yes
    A*6601X0.10 (0.01–0.98)
    A*68010.62 (0.38–0.99)3.32 (1.14–9.64)4.83 (1.02–22.6)3No
    B*08010.68 (0.62–0.74)
    B*18011.58 (1.31–1.90)1.74 (1.19–2.53)2Yes
    B*3501X4.79 (1.07–21.4)4.79 (1.07–21.4)2No
    B*3503XX14.54 (2.66–79.3)
    B*3801X0.70 (0.49–0.97)X
    B*3901XX2.44 (1.01–5.88)
    B*390611.56 (0.68–195.0)†2.70 (1.16–6.29)14.03 (5.55–35.4)7.15 (3.89–13.1)14.54 (2.66–79.3)4Yes
    B*40010.71 (0.56–0.88)
    B*44020.34 (0.13–0.84)
    B*44034.83 (1.12–20.6)0.5 (0.32–0.77)XX2No
    B*4901X1.61 (1.01–2.53)XXX
    B*50011.95 (1.22–3.11)XXX
    B*51010.36 (0.13–0.96)
    B*5301XXXX28.11 (1.75–449.0)
    B*56010.10 (0.01–0.81)XXXX
    C*01020.30 (0.11–0.77)
    C*04014.82 (1.87–12.3)
    C*05011.48 (1.21–1.81)0.29 (0.12–0.68)2No
    C*06021.56 (1.09–2.21)X
    C*07010.70 (0.60–0.80)0.26 (0.08–0.80)0.51 (0.28–0.92)3Yes
    C*07021.31 (1.00–1.70)3.65 (2.42–5.48)1.94 (1.41–2.65)3Yes
    C*1202X0.15 (0.03–0.61)XXX
    C*1402X0.33 (0.11–0.92)X
    C*15020.57 (0.37–0.87)X
    C*1604X0.38 (0.15–0.90)
    • For each allele, the relative OR value represents a comparison of the DR haplotype carrying the allele to that DR haplotype carrying any class I allele. X = total n in contingency table ≤12.

    • †Although the confidence interval overlaps 1, this result, with relative OR of 11.56, has been included for comparison. Data for seven alleles that exhibit a consistent disease association on more than one haplotype are indicated in boldface type.

PreviousNext
Back to top

In this Issue

November 2010, 59(11)
  • Table of Contents
  • Index by Author
Sign up to receive current issue alerts
View Selected Citations (0)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about Diabetes.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
HLA Class I and Genetic Susceptibility to Type 1 Diabetes
(Your Name) has forwarded a page to you from Diabetes
(Your Name) thought you would like to see this page from the Diabetes web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
HLA Class I and Genetic Susceptibility to Type 1 Diabetes
Janelle A. Noble, Ana Maria Valdes, Michael D. Varney, Joyce A. Carlson, Priscilla Moonsamy, Anna Lisa Fear, Julie A. Lane, Eva Lavant, Rebecca Rappner, Anthony Louey, Patrick Concannon, Josyf C. Mychaleckyj, Henry A. Erlich, for the Type 1 Diabetes Genetics Consortium
Diabetes Nov 2010, 59 (11) 2972-2979; DOI: 10.2337/db10-0699

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Add to Selected Citations
Share

HLA Class I and Genetic Susceptibility to Type 1 Diabetes
Janelle A. Noble, Ana Maria Valdes, Michael D. Varney, Joyce A. Carlson, Priscilla Moonsamy, Anna Lisa Fear, Julie A. Lane, Eva Lavant, Rebecca Rappner, Anthony Louey, Patrick Concannon, Josyf C. Mychaleckyj, Henry A. Erlich, for the Type 1 Diabetes Genetics Consortium
Diabetes Nov 2010, 59 (11) 2972-2979; DOI: 10.2337/db10-0699
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • RESEARCH DESIGN AND METHODS
    • RESULTS
    • DISCUSSION
    • ACKNOWLEDGMENTS
    • Footnotes
    • REFERENCES
  • Figures & Tables
  • Suppl Material
  • Info & Metrics
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • PTPN2, a Candidate Gene for Type 1 Diabetes, Modulates Pancreatic β-Cell Apoptosis via Regulation of the BH3-Only Protein Bim
  • Single Insulin-Specific CD8+ T Cells Show Characteristic Gene Expression Profiles in Human Type 1 Diabetes
  • Cesarean Section and Interferon-Induced Helicase Gene Polymorphisms Combine to Increase Childhood Type 1 Diabetes Risk
Show more Genetics

Similar Articles

Navigate

  • Current Issue
  • Online Ahead of Print
  • Scientific Sessions Abstracts
  • Collections
  • Archives
  • Submit
  • Subscribe
  • Email Alerts
  • RSS Feeds

More Information

  • About the Journal
  • Instructions for Authors
  • Journal Policies
  • Reprints and Permissions
  • Advertising
  • Privacy Policy: ADA Journals
  • Copyright Notice/Public Access Policy
  • Contact Us

Other ADA Resources

  • Diabetes Care
  • Clinical Diabetes
  • Diabetes Spectrum
  • Scientific Sessions Abstracts
  • Standards of Medical Care in Diabetes
  • BMJ Open - Diabetes Research & Care
  • Professional Books
  • Diabetes Forecast

 

  • DiabetesJournals.org
  • Diabetes Core Update
  • ADA's DiabetesPro
  • ADA Member Directory
  • Diabetes.org

© 2021 by the American Diabetes Association. Diabetes Print ISSN: 0012-1797, Online ISSN: 1939-327X.