Comprehensive Genotyping in Two Homogeneous Graves' Disease Samples Reveals Major and Novel HLA Association Alleles

Graves' disease (GD) is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies showed relatively higher prevalence of GD in Asians than in Caucasians, previous genetic studies were contradictory concerning whether and/or which...

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Published inPloS one Vol. 6; no. 1; p. e16635
Main Authors Chen, Pei-Lung, Fann, Cathy Shen-Jang, Chu, Chen-Chung, Chang, Chien-Ching, Chang, Su-Wei, Hsieh, Hsin-Yi, Lin, Marie, Yang, Wei-Shiung, Chang, Tien-Chun
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 28.01.2011
Public Library of Science (PLoS)
Subjects
Alleles
Analysis
Arthritis
Asian Continental Ancestry Group - genetics
Biology
Biometrics
Case-Control Studies
Disease
DNA fingerprints
Drb1 protein
Eye
Eye diseases
Family
Genetic aspects
Genetic diversity
Genetic Predisposition to Disease
Genomes
Genotype
Genotyping
Graves Disease - ethnology
Graves Disease - genetics
Graves' disease
Haplotypes
Heterogeneity
Histocompatibility antigen HLA
HLA antigens
HLA Antigens - genetics
HLA-DP Antigens
HLA-DR Antigens
Hospitals
Humans
Hyperthyroidism
Hypotheses
Hypothyroidism
Internal medicine
Laboratories
Leukocytes
Lupus
Medical research
Medicine
Population
Population genetics
Populations
Prevalence studies (Epidemiology)
Studies
Taiwan
Thyroid
Thyroid gland
Thyroid hormones
Values
White people
Working groups
Taiwan
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Abstract Graves' disease (GD) is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies showed relatively higher prevalence of GD in Asians than in Caucasians, previous genetic studies were contradictory concerning whether and/or which human leukocyte antigen (HLA) alleles are associated with GD in Asians. We conducted a case-control association study (499 unrelated GD cases and 504 controls) and a replication in an independent family sample (419 GD individuals and their 282 relatives in 165 families). To minimize genetic and phenotypic heterogeneity, we included only ethnic Chinese Han population in Taiwan and excluded subjects with hypothyroidism. We performed direct and comprehensive genotyping of six classical HLA loci (HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1) to 4-digit resolution. Combining the data of two sample populations, we found that B*46:01 (odds ratio under dominant model [OR]  = 1.33, Bonferroni corrected combined P [P(Bc)]  = 1.17 x 10⁻²), DPB1*05:01 (OR  = 2.34, P(Bc) = 2.58 x 10⁻¹⁰), DQB1*03:02 (OR  = 0.62, P(Bc)  = 1.97 x 10⁻²), DRB1*15:01 (OR  = 1.68, P(Bc) = 1.22 x 10⁻²) and DRB1*16:02 (OR  = 2.63, P(Bc)  = 1.46 x 10⁻⁵) were associated with GD. HLA-DPB1*05:01 is the major gene of GD in our population and singly accounts for 48.4% of population-attributable risk. These GD-associated alleles we identified in ethnic Chinese Hans, and those identified in other Asian studies, are totally distinct from the known associated alleles in Caucasians. Identification of population-specific association alleles is the critical first step for individualized medicine. Furthermore, comparison between different susceptibility/protective alleles across populations could facilitate generation of novel hypothesis about GD pathophysiology and indicate a new direction for future investigation.
AbstractList Background Graves' disease (GD) is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies showed relatively higher prevalence of GD in Asians than in Caucasians, previous genetic studies were contradictory concerning whether and/or which human leukocyte antigen (HLA) alleles are associated with GD in Asians. Methodology/Principal Findings We conducted a case-control association study (499 unrelated GD cases and 504 controls) and a replication in an independent family sample (419 GD individuals and their 282 relatives in 165 families). To minimize genetic and phenotypic heterogeneity, we included only ethnic Chinese Han population in Taiwan and excluded subjects with hypothyroidism. We performed direct and comprehensive genotyping of six classical HLA loci (HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1) to 4-digit resolution. Combining the data of two sample populations, we found that B*46:01 (odds ratio under dominant model [OR]  = 1.33, Bonferroni corrected combined P [PBc]  = 1.17×10−2), DPB1*05:01 (OR  = 2.34, PBc = 2.58×10−10), DQB1*03:02 (OR  = 0.62, PBc  = 1.97×10−2), DRB1*15:01 (OR  = 1.68, PBc = 1.22×10−2) and DRB1*16:02 (OR  = 2.63, PBc  = 1.46×10−5) were associated with GD. HLA-DPB1*05:01 is the major gene of GD in our population and singly accounts for 48.4% of population-attributable risk. Conclusions/Significance These GD-associated alleles we identified in ethnic Chinese Hans, and those identified in other Asian studies, are totally distinct from the known associated alleles in Caucasians. Identification of population-specific association alleles is the critical first step for individualized medicine. Furthermore, comparison between different susceptibility/protective alleles across populations could facilitate generation of novel hypothesis about GD pathophysiology and indicate a new direction for future investigation.
Graves' disease (GD) is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies showed relatively higher prevalence of GD in Asians than in Caucasians, previous genetic studies were contradictory concerning whether and/or which human leukocyte antigen (HLA) alleles are associated with GD in Asians. We conducted a case-control association study (499 unrelated GD cases and 504 controls) and a replication in an independent family sample (419 GD individuals and their 282 relatives in 165 families). To minimize genetic and phenotypic heterogeneity, we included only ethnic Chinese Han population in Taiwan and excluded subjects with hypothyroidism. We performed direct and comprehensive genotyping of six classical HLA loci (HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1) to 4-digit resolution. Combining the data of two sample populations, we found that B*46:01 (odds ratio under dominant model [OR] = 1.33, Bonferroni corrected combined P [P.sub.Bc ] = 1.17x10.sup.-2 ), DPB1*05:01 (OR = 2.34, P.sub.Bc = 2.58x10.sup.-10 ), DQB1*03:02 (OR = 0.62, P.sub.Bc = 1.97x10.sup.-2 ), DRB1*15:01 (OR = 1.68, P.sub.Bc = 1.22x10.sup.-2) and DRB1*16:02 (OR = 2.63, P.sub.Bc = 1.46x10.sup.-5) were associated with GD. HLA-DPB1*05:01 is the major gene of GD in our population and singly accounts for 48.4% of population-attributable risk. These GD-associated alleles we identified in ethnic Chinese Hans, and those identified in other Asian studies, are totally distinct from the known associated alleles in Caucasians. Identification of population-specific association alleles is the critical first step for individualized medicine. Furthermore, comparison between different susceptibility/protective alleles across populations could facilitate generation of novel hypothesis about GD pathophysiology and indicate a new direction for future investigation.
Graves' disease (GD) is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies showed relatively higher prevalence of GD in Asians than in Caucasians, previous genetic studies were contradictory concerning whether and/or which human leukocyte antigen (HLA) alleles are associated with GD in Asians. We conducted a case-control association study (499 unrelated GD cases and 504 controls) and a replication in an independent family sample (419 GD individuals and their 282 relatives in 165 families). To minimize genetic and phenotypic heterogeneity, we included only ethnic Chinese Han population in Taiwan and excluded subjects with hypothyroidism. We performed direct and comprehensive genotyping of six classical HLA loci (HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1) to 4-digit resolution. Combining the data of two sample populations, we found that B*46:01 (odds ratio under dominant model [OR]  = 1.33, Bonferroni corrected combined P [P(Bc)]  = 1.17 x 10⁻²), DPB1*05:01 (OR  = 2.34, P(Bc) = 2.58 x 10⁻¹⁰), DQB1*03:02 (OR  = 0.62, P(Bc)  = 1.97 x 10⁻²), DRB1*15:01 (OR  = 1.68, P(Bc) = 1.22 x 10⁻²) and DRB1*16:02 (OR  = 2.63, P(Bc)  = 1.46 x 10⁻⁵) were associated with GD. HLA-DPB1*05:01 is the major gene of GD in our population and singly accounts for 48.4% of population-attributable risk. These GD-associated alleles we identified in ethnic Chinese Hans, and those identified in other Asian studies, are totally distinct from the known associated alleles in Caucasians. Identification of population-specific association alleles is the critical first step for individualized medicine. Furthermore, comparison between different susceptibility/protective alleles across populations could facilitate generation of novel hypothesis about GD pathophysiology and indicate a new direction for future investigation.
Graves' disease (GD) is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies showed relatively higher prevalence of GD in Asians than in Caucasians, previous genetic studies were contradictory concerning whether and/or which human leukocyte antigen (HLA) alleles are associated with GD in Asians.BACKGROUNDGraves' disease (GD) is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies showed relatively higher prevalence of GD in Asians than in Caucasians, previous genetic studies were contradictory concerning whether and/or which human leukocyte antigen (HLA) alleles are associated with GD in Asians.We conducted a case-control association study (499 unrelated GD cases and 504 controls) and a replication in an independent family sample (419 GD individuals and their 282 relatives in 165 families). To minimize genetic and phenotypic heterogeneity, we included only ethnic Chinese Han population in Taiwan and excluded subjects with hypothyroidism. We performed direct and comprehensive genotyping of six classical HLA loci (HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1) to 4-digit resolution. Combining the data of two sample populations, we found that B*46:01 (odds ratio under dominant model [OR]  = 1.33, Bonferroni corrected combined P [P(Bc)]  = 1.17 x 10⁻²), DPB1*05:01 (OR  = 2.34, P(Bc) = 2.58 x 10⁻¹⁰), DQB1*03:02 (OR  = 0.62, P(Bc)  = 1.97 x 10⁻²), DRB1*15:01 (OR  = 1.68, P(Bc) = 1.22 x 10⁻²) and DRB1*16:02 (OR  = 2.63, P(Bc)  = 1.46 x 10⁻⁵) were associated with GD. HLA-DPB1*05:01 is the major gene of GD in our population and singly accounts for 48.4% of population-attributable risk.METHODOLOGY/PRINCIPAL FINDINGSWe conducted a case-control association study (499 unrelated GD cases and 504 controls) and a replication in an independent family sample (419 GD individuals and their 282 relatives in 165 families). To minimize genetic and phenotypic heterogeneity, we included only ethnic Chinese Han population in Taiwan and excluded subjects with hypothyroidism. We performed direct and comprehensive genotyping of six classical HLA loci (HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1) to 4-digit resolution. Combining the data of two sample populations, we found that B*46:01 (odds ratio under dominant model [OR]  = 1.33, Bonferroni corrected combined P [P(Bc)]  = 1.17 x 10⁻²), DPB1*05:01 (OR  = 2.34, P(Bc) = 2.58 x 10⁻¹⁰), DQB1*03:02 (OR  = 0.62, P(Bc)  = 1.97 x 10⁻²), DRB1*15:01 (OR  = 1.68, P(Bc) = 1.22 x 10⁻²) and DRB1*16:02 (OR  = 2.63, P(Bc)  = 1.46 x 10⁻⁵) were associated with GD. HLA-DPB1*05:01 is the major gene of GD in our population and singly accounts for 48.4% of population-attributable risk.These GD-associated alleles we identified in ethnic Chinese Hans, and those identified in other Asian studies, are totally distinct from the known associated alleles in Caucasians. Identification of population-specific association alleles is the critical first step for individualized medicine. Furthermore, comparison between different susceptibility/protective alleles across populations could facilitate generation of novel hypothesis about GD pathophysiology and indicate a new direction for future investigation.CONCLUSIONS/SIGNIFICANCEThese GD-associated alleles we identified in ethnic Chinese Hans, and those identified in other Asian studies, are totally distinct from the known associated alleles in Caucasians. Identification of population-specific association alleles is the critical first step for individualized medicine. Furthermore, comparison between different susceptibility/protective alleles across populations could facilitate generation of novel hypothesis about GD pathophysiology and indicate a new direction for future investigation.
Background Graves' disease (GD) is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies showed relatively higher prevalence of GD in Asians than in Caucasians, previous genetic studies were contradictory concerning whether and/or which human leukocyte antigen (HLA) alleles are associated with GD in Asians. Methodology/Principal Findings We conducted a case-control association study (499 unrelated GD cases and 504 controls) and a replication in an independent family sample (419 GD individuals and their 282 relatives in 165 families). To minimize genetic and phenotypic heterogeneity, we included only ethnic Chinese Han population in Taiwan and excluded subjects with hypothyroidism. We performed direct and comprehensive genotyping of six classical HLA loci (HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1) to 4-digit resolution. Combining the data of two sample populations, we found that B*46:01 (odds ratio under dominant model [OR]  = 1.33, Bonferroni corrected combined P [PBc]  = 1.17×10−2), DPB1*05:01 (OR  = 2.34, PBc = 2.58×10−10), DQB1*03:02 (OR  = 0.62, PBc  = 1.97×10−2), DRB1*15:01 (OR  = 1.68, PBc = 1.22×10−2) and DRB1*16:02 (OR  = 2.63, PBc  = 1.46×10−5) were associated with GD. HLA-DPB1*05:01 is the major gene of GD in our population and singly accounts for 48.4% of population-attributable risk. Conclusions/Significance These GD-associated alleles we identified in ethnic Chinese Hans, and those identified in other Asian studies, are totally distinct from the known associated alleles in Caucasians. Identification of population-specific association alleles is the critical first step for individualized medicine. Furthermore, comparison between different susceptibility/protective alleles across populations could facilitate generation of novel hypothesis about GD pathophysiology and indicate a new direction for future investigation.
BACKGROUND: Graves' disease (GD) is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies showed relatively higher prevalence of GD in Asians than in Caucasians, previous genetic studies were contradictory concerning whether and/or which human leukocyte antigen (HLA) alleles are associated with GD in Asians. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a case-control association study (499 unrelated GD cases and 504 controls) and a replication in an independent family sample (419 GD individuals and their 282 relatives in 165 families). To minimize genetic and phenotypic heterogeneity, we included only ethnic Chinese Han population in Taiwan and excluded subjects with hypothyroidism. We performed direct and comprehensive genotyping of six classical HLA loci (HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1) to 4-digit resolution. Combining the data of two sample populations, we found that B*46:01 (odds ratio under dominant model [OR]  = 1.33, Bonferroni corrected combined P [P(Bc)]  = 1.17 x 10⁻²), DPB1*05:01 (OR  = 2.34, P(Bc) = 2.58 x 10⁻¹⁰), DQB1*03:02 (OR  = 0.62, P(Bc)  = 1.97 x 10⁻²), DRB1*15:01 (OR  = 1.68, P(Bc) = 1.22 x 10⁻²) and DRB1*16:02 (OR  = 2.63, P(Bc)  = 1.46 x 10⁻⁵) were associated with GD. HLA-DPB1*05:01 is the major gene of GD in our population and singly accounts for 48.4% of population-attributable risk. CONCLUSIONS/SIGNIFICANCE: These GD-associated alleles we identified in ethnic Chinese Hans, and those identified in other Asian studies, are totally distinct from the known associated alleles in Caucasians. Identification of population-specific association alleles is the critical first step for individualized medicine. Furthermore, comparison between different susceptibility/protective alleles across populations could facilitate generation of novel hypothesis about GD pathophysiology and indicate a new direction for future investigation.
Graves' disease (GD) is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies showed relatively higher prevalence of GD in Asians than in Caucasians, previous genetic studies were contradictory concerning whether and/or which human leukocyte antigen (HLA) alleles are associated with GD in Asians. We conducted a case-control association study (499 unrelated GD cases and 504 controls) and a replication in an independent family sample (419 GD individuals and their 282 relatives in 165 families). To minimize genetic and phenotypic heterogeneity, we included only ethnic Chinese Han population in Taiwan and excluded subjects with hypothyroidism. We performed direct and comprehensive genotyping of six classical HLA loci (HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1) to 4-digit resolution. Combining the data of two sample populations, we found that B*46:01 (odds ratio under dominant model [OR] =1.33, Bonferroni corrected combined P [PBc] =1.1710-2), DPB1*05:01 (OR =2.34, PBc=2.5810-10), DQB1*03:02 (OR =0.62, PBc =1.9710-2), DRB1*15:01 (OR =1.68, PBc=1.2210-2) and DRB1*16:02 (OR =2.63, PBc =1.4610-5) were associated with GD. HLA-DPB1*05:01 is the major gene of GD in our population and singly accounts for 48.4% of population-attributable risk. These GD-associated alleles we identified in ethnic Chinese Hans, and those identified in other Asian studies, are totally distinct from the known associated alleles in Caucasians. Identification of population-specific association alleles is the critical first step for individualized medicine. Furthermore, comparison between different susceptibility/protective alleles across populations could facilitate generation of novel hypothesis about GD pathophysiology and indicate a new direction for future investigation.
Background Graves' disease (GD) is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies showed relatively higher prevalence of GD in Asians than in Caucasians, previous genetic studies were contradictory concerning whether and/or which human leukocyte antigen (HLA) alleles are associated with GD in Asians. Methodology/Principal Findings We conducted a case-control association study (499 unrelated GD cases and 504 controls) and a replication in an independent family sample (419 GD individuals and their 282 relatives in 165 families). To minimize genetic and phenotypic heterogeneity, we included only ethnic Chinese Han population in Taiwan and excluded subjects with hypothyroidism. We performed direct and comprehensive genotyping of six classical HLA loci (HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1) to 4-digit resolution. Combining the data of two sample populations, we found that B*46:01 (odds ratio under dominant model [OR] = 1.33, Bonferroni corrected combined P [P.sub.Bc ] = 1.17x10.sup.-2 ), DPB1*05:01 (OR = 2.34, P.sub.Bc = 2.58x10.sup.-10 ), DQB1*03:02 (OR = 0.62, P.sub.Bc = 1.97x10.sup.-2 ), DRB1*15:01 (OR = 1.68, P.sub.Bc = 1.22x10.sup.-2) and DRB1*16:02 (OR = 2.63, P.sub.Bc = 1.46x10.sup.-5) were associated with GD. HLA-DPB1*05:01 is the major gene of GD in our population and singly accounts for 48.4% of population-attributable risk. Conclusions/Significance These GD-associated alleles we identified in ethnic Chinese Hans, and those identified in other Asian studies, are totally distinct from the known associated alleles in Caucasians. Identification of population-specific association alleles is the critical first step for individualized medicine. Furthermore, comparison between different susceptibility/protective alleles across populations could facilitate generation of novel hypothesis about GD pathophysiology and indicate a new direction for future investigation.
Audience Academic
Author Chen, Pei-Lung
Chang, Chien-Ching
Chang, Su-Wei
Chu, Chen-Chung
Hsieh, Hsin-Yi
Yang, Wei-Shiung
Chang, Tien-Chun
Fann, Cathy Shen-Jang
Lin, Marie
AuthorAffiliation 2 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
3 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
6 Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
4 Institute of Public Health, National Yang-Ming University, Taipei, Taiwan
1 Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan
7 Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
La Jolla Institute of Allergy and Immunology, United States of America
5 Transfusion Medicine Laboratory, Medical Research Department, Mackay Memorial Hospital, Taipei, Taiwan
AuthorAffiliation_xml – name: 5 Transfusion Medicine Laboratory, Medical Research Department, Mackay Memorial Hospital, Taipei, Taiwan
– name: 6 Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
– name: 1 Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan
– name: 3 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
– name: La Jolla Institute of Allergy and Immunology, United States of America
– name: 2 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
– name: 4 Institute of Public Health, National Yang-Ming University, Taipei, Taiwan
– name: 7 Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
Author_xml – sequence: 1
  givenname: Pei-Lung
  surname: Chen
  fullname: Chen, Pei-Lung
– sequence: 2
  givenname: Cathy Shen-Jang
  surname: Fann
  fullname: Fann, Cathy Shen-Jang
– sequence: 3
  givenname: Chen-Chung
  surname: Chu
  fullname: Chu, Chen-Chung
– sequence: 4
  givenname: Chien-Ching
  surname: Chang
  fullname: Chang, Chien-Ching
– sequence: 5
  givenname: Su-Wei
  surname: Chang
  fullname: Chang, Su-Wei
– sequence: 6
  givenname: Hsin-Yi
  surname: Hsieh
  fullname: Hsieh, Hsin-Yi
– sequence: 7
  givenname: Marie
  surname: Lin
  fullname: Lin, Marie
– sequence: 8
  givenname: Wei-Shiung
  surname: Yang
  fullname: Yang, Wei-Shiung
– sequence: 9
  givenname: Tien-Chun
  surname: Chang
  fullname: Chang, Tien-Chun
BackLink https://www.ncbi.nlm.nih.gov/pubmed/21307958$$D View this record in MEDLINE/PubMed
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Conceived and designed the experiments: P-LC CS-JF W-SY T-CC. Performed the experiments: P-LC C-C Chu T-CC. Analyzed the data: P-LC CS-JF C-C Chu C-C Chang H-YH S-WC ML. Contributed reagents/materials/analysis tools: CS-JF C-C Chu ML W-SY. Wrote the paper: P-LC CS-JF W-SY T-CC.
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Snippet Graves' disease (GD) is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies showed...
Background Graves' disease (GD) is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies...
BACKGROUND: Graves' disease (GD) is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies...
Background Graves' disease (GD) is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies...
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SubjectTerms Alleles
Analysis
Arthritis
Asian Continental Ancestry Group - genetics
Biology
Biometrics
Case-Control Studies
Disease
DNA fingerprints
Drb1 protein
Eye
Eye diseases
Family
Genetic aspects
Genetic diversity
Genetic Predisposition to Disease
Genomes
Genotype
Genotyping
Graves Disease - ethnology
Graves Disease - genetics
Graves' disease
Haplotypes
Heterogeneity
Histocompatibility antigen HLA
HLA antigens
HLA Antigens - genetics
HLA-DP Antigens
HLA-DR Antigens
Hospitals
Humans
Hyperthyroidism
Hypotheses
Hypothyroidism
Internal medicine
Laboratories
Leukocytes
Lupus
Medical research
Medicine
Population
Population genetics
Populations
Prevalence studies (Epidemiology)
Studies
Taiwan
Thyroid
Thyroid gland
Thyroid hormones
Values
White people
Working groups
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Title Comprehensive Genotyping in Two Homogeneous Graves' Disease Samples Reveals Major and Novel HLA Association Alleles
URI https://www.ncbi.nlm.nih.gov/pubmed/21307958
https://www.proquest.com/docview/1294325028
https://www.proquest.com/docview/851475827
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https://pubmed.ncbi.nlm.nih.gov/PMC3030609
https://doaj.org/article/73193dd9b6384e108f3f5ae50af91c5c
http://dx.doi.org/10.1371/journal.pone.0016635
Volume 6
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