Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression

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Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression. / Glanville, Kylie P.; Coleman, Jonathan R.I.; Hanscombe, Ken B.; Euesden, Jack; Choi, Shing Wan; Purves, Kirstin L.; Breen, Gerome; Air, Tracy M.; Andlauer, Till F.M.; Baune, Bernhard T.; Binder, Elisabeth B.; Blackwood, Douglas H.R.; Boomsma, Dorret I.; Buttenschøn, Henriette N.; Colodro-Conde, Lucía; Dannlowski, Udo; Direk, Nese; Dunn, Erin C.; Forstner, Andreas J.; de Geus, Eco J.C.; Grabe, Hans J.; Hamilton, Steven P.; Jones, Ian; Jones, Lisa A.; Knowles, James A.; Kutalik, Zoltán; Levinson, Douglas F.; Lewis, Glyn; Lind, Penelope A.; Lucae, Susanne; Magnusson, Patrik K.; McGuffin, Peter; McIntosh, Andrew M.; Milaneschi, Yuri; Mors, Ole; Mostafavi, Sara; Müller-Myhsok, Bertram; Pedersen, Nancy L.; Penninx, Brenda W.J.H.; Potash, James B.; Preisig, Martin; Ripke, Stephan; Shi, Jianxin; Bækvad-Hansen, Marie; Hansen, Christine Søholm; Hansen, Thomas F.; Pedersen, Carsten Bøcker; Pedersen, Marianne Giørtz; Nordentoft, Merete; Werge, Thomas; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.

In: Biological Psychiatry, Vol. 87, No. 5, 2020, p. 419-430.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Glanville, KP, Coleman, JRI, Hanscombe, KB, Euesden, J, Choi, SW, Purves, KL, Breen, G, Air, TM, Andlauer, TFM, Baune, BT, Binder, EB, Blackwood, DHR, Boomsma, DI, Buttenschøn, HN, Colodro-Conde, L, Dannlowski, U, Direk, N, Dunn, EC, Forstner, AJ, de Geus, EJC, Grabe, HJ, Hamilton, SP, Jones, I, Jones, LA, Knowles, JA, Kutalik, Z, Levinson, DF, Lewis, G, Lind, PA, Lucae, S, Magnusson, PK, McGuffin, P, McIntosh, AM, Milaneschi, Y, Mors, O, Mostafavi, S, Müller-Myhsok, B, Pedersen, NL, Penninx, BWJH, Potash, JB, Preisig, M, Ripke, S, Shi, J, Bækvad-Hansen, M, Hansen, CS, Hansen, TF, Pedersen, CB, Pedersen, MG, Nordentoft, M, Werge, T & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium 2020, 'Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression', Biological Psychiatry, vol. 87, no. 5, pp. 419-430. https://doi.org/10.1016/j.biopsych.2019.06.031

APA

Glanville, K. P., Coleman, J. R. I., Hanscombe, K. B., Euesden, J., Choi, S. W., Purves, K. L., Breen, G., Air, T. M., Andlauer, T. F. M., Baune, B. T., Binder, E. B., Blackwood, D. H. R., Boomsma, D. I., Buttenschøn, H. N., Colodro-Conde, L., Dannlowski, U., Direk, N., Dunn, E. C., Forstner, A. J., ... Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (2020). Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression. Biological Psychiatry, 87(5), 419-430. https://doi.org/10.1016/j.biopsych.2019.06.031

Vancouver

Glanville KP, Coleman JRI, Hanscombe KB, Euesden J, Choi SW, Purves KL et al. Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression. Biological Psychiatry. 2020;87(5):419-430. https://doi.org/10.1016/j.biopsych.2019.06.031

Author

Glanville, Kylie P. ; Coleman, Jonathan R.I. ; Hanscombe, Ken B. ; Euesden, Jack ; Choi, Shing Wan ; Purves, Kirstin L. ; Breen, Gerome ; Air, Tracy M. ; Andlauer, Till F.M. ; Baune, Bernhard T. ; Binder, Elisabeth B. ; Blackwood, Douglas H.R. ; Boomsma, Dorret I. ; Buttenschøn, Henriette N. ; Colodro-Conde, Lucía ; Dannlowski, Udo ; Direk, Nese ; Dunn, Erin C. ; Forstner, Andreas J. ; de Geus, Eco J.C. ; Grabe, Hans J. ; Hamilton, Steven P. ; Jones, Ian ; Jones, Lisa A. ; Knowles, James A. ; Kutalik, Zoltán ; Levinson, Douglas F. ; Lewis, Glyn ; Lind, Penelope A. ; Lucae, Susanne ; Magnusson, Patrik K. ; McGuffin, Peter ; McIntosh, Andrew M. ; Milaneschi, Yuri ; Mors, Ole ; Mostafavi, Sara ; Müller-Myhsok, Bertram ; Pedersen, Nancy L. ; Penninx, Brenda W.J.H. ; Potash, James B. ; Preisig, Martin ; Ripke, Stephan ; Shi, Jianxin ; Bækvad-Hansen, Marie ; Hansen, Christine Søholm ; Hansen, Thomas F. ; Pedersen, Carsten Bøcker ; Pedersen, Marianne Giørtz ; Nordentoft, Merete ; Werge, Thomas ; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. / Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression. In: Biological Psychiatry. 2020 ; Vol. 87, No. 5. pp. 419-430.

Bibtex

@article{0117918125d64b85a733e8bec9e2131d,
title = "Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression",
abstract = "Background: The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression. Methods: We fine-mapped the classical MHC (chr6: 29.6–33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10−6) and a candidate threshold (1.6 × 10−4). Results: No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97–0.99). Conclusions: We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.",
keywords = "Autoimmune disorder, Complement, Genetic association, Human leukocyte antigen, Major depressive disorder, Major histocompatibility complex",
author = "Glanville, {Kylie P.} and Coleman, {Jonathan R.I.} and Hanscombe, {Ken B.} and Jack Euesden and Choi, {Shing Wan} and Purves, {Kirstin L.} and Gerome Breen and Air, {Tracy M.} and Andlauer, {Till F.M.} and Baune, {Bernhard T.} and Binder, {Elisabeth B.} and Blackwood, {Douglas H.R.} and Boomsma, {Dorret I.} and Buttensch{\o}n, {Henriette N.} and Luc{\'i}a Colodro-Conde and Udo Dannlowski and Nese Direk and Dunn, {Erin C.} and Forstner, {Andreas J.} and {de Geus}, {Eco J.C.} and Grabe, {Hans J.} and Hamilton, {Steven P.} and Ian Jones and Jones, {Lisa A.} and Knowles, {James A.} and Zolt{\'a}n Kutalik and Levinson, {Douglas F.} and Glyn Lewis and Lind, {Penelope A.} and Susanne Lucae and Magnusson, {Patrik K.} and Peter McGuffin and McIntosh, {Andrew M.} and Yuri Milaneschi and Ole Mors and Sara Mostafavi and Bertram M{\"u}ller-Myhsok and Pedersen, {Nancy L.} and Penninx, {Brenda W.J.H.} and Potash, {James B.} and Martin Preisig and Stephan Ripke and Jianxin Shi and Marie B{\ae}kvad-Hansen and Hansen, {Christine S{\o}holm} and Hansen, {Thomas F.} and Pedersen, {Carsten B{\o}cker} and Pedersen, {Marianne Gi{\o}rtz} and Merete Nordentoft and Thomas Werge and {Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium}",
year = "2020",
doi = "10.1016/j.biopsych.2019.06.031",
language = "English",
volume = "87",
pages = "419--430",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier",
number = "5",

}

RIS

TY - JOUR

T1 - Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression

AU - Glanville, Kylie P.

AU - Coleman, Jonathan R.I.

AU - Hanscombe, Ken B.

AU - Euesden, Jack

AU - Choi, Shing Wan

AU - Purves, Kirstin L.

AU - Breen, Gerome

AU - Air, Tracy M.

AU - Andlauer, Till F.M.

AU - Baune, Bernhard T.

AU - Binder, Elisabeth B.

AU - Blackwood, Douglas H.R.

AU - Boomsma, Dorret I.

AU - Buttenschøn, Henriette N.

AU - Colodro-Conde, Lucía

AU - Dannlowski, Udo

AU - Direk, Nese

AU - Dunn, Erin C.

AU - Forstner, Andreas J.

AU - de Geus, Eco J.C.

AU - Grabe, Hans J.

AU - Hamilton, Steven P.

AU - Jones, Ian

AU - Jones, Lisa A.

AU - Knowles, James A.

AU - Kutalik, Zoltán

AU - Levinson, Douglas F.

AU - Lewis, Glyn

AU - Lind, Penelope A.

AU - Lucae, Susanne

AU - Magnusson, Patrik K.

AU - McGuffin, Peter

AU - McIntosh, Andrew M.

AU - Milaneschi, Yuri

AU - Mors, Ole

AU - Mostafavi, Sara

AU - Müller-Myhsok, Bertram

AU - Pedersen, Nancy L.

AU - Penninx, Brenda W.J.H.

AU - Potash, James B.

AU - Preisig, Martin

AU - Ripke, Stephan

AU - Shi, Jianxin

AU - Bækvad-Hansen, Marie

AU - Hansen, Christine Søholm

AU - Hansen, Thomas F.

AU - Pedersen, Carsten Bøcker

AU - Pedersen, Marianne Giørtz

AU - Nordentoft, Merete

AU - Werge, Thomas

AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

PY - 2020

Y1 - 2020

N2 - Background: The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression. Methods: We fine-mapped the classical MHC (chr6: 29.6–33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10−6) and a candidate threshold (1.6 × 10−4). Results: No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97–0.99). Conclusions: We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.

AB - Background: The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression. Methods: We fine-mapped the classical MHC (chr6: 29.6–33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10−6) and a candidate threshold (1.6 × 10−4). Results: No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97–0.99). Conclusions: We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.

KW - Autoimmune disorder

KW - Complement

KW - Genetic association

KW - Human leukocyte antigen

KW - Major depressive disorder

KW - Major histocompatibility complex

U2 - 10.1016/j.biopsych.2019.06.031

DO - 10.1016/j.biopsych.2019.06.031

M3 - Journal article

C2 - 31570195

AN - SCOPUS:85072749953

VL - 87

SP - 419

EP - 430

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 5

ER -

ID: 259048038