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Cross-disorder analysis of schizophrenia and 19 immune-mediated diseases identifies shared genetic risk

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Cross-disorder analysis of schizophrenia and 19 immune-mediated diseases identifies shared genetic risk. / Pouget, Jennie G; Han, Buhm; Wu, Yang et al.
In: Human Molecular Genetics, Vol. 28, No. 20, 15.10.2019, p. 3498-3513.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Pouget, JG, Han, B, Wu, Y, Mignot, E, Ollila, HM, Barker, J, Spain, S, Dand, N, Trembath, R, Martin, J, Mayes, MD, Bossini-Castillo, L, López-Isac, E, Jin, Y, Santorico, SA, Spritz, RA, Hakonarson, H, Polychronakos, C, Raychaudhuri, S, Knight, J & Schizophrenia Working Group of the Psychiatric Genomics Consortium 2019, 'Cross-disorder analysis of schizophrenia and 19 immune-mediated diseases identifies shared genetic risk', Human Molecular Genetics, vol. 28, no. 20, pp. 3498-3513. https://doi.org/10.1093/hmg/ddz145

APA

Pouget, J. G., Han, B., Wu, Y., Mignot, E., Ollila, H. M., Barker, J., Spain, S., Dand, N., Trembath, R., Martin, J., Mayes, M. D., Bossini-Castillo, L., López-Isac, E., Jin, Y., Santorico, S. A., Spritz, R. A., Hakonarson, H., Polychronakos, C., Raychaudhuri, S., ... Schizophrenia Working Group of the Psychiatric Genomics Consortium (2019). Cross-disorder analysis of schizophrenia and 19 immune-mediated diseases identifies shared genetic risk. Human Molecular Genetics, 28(20), 3498-3513. https://doi.org/10.1093/hmg/ddz145

Vancouver

Pouget JG, Han B, Wu Y, Mignot E, Ollila HM, Barker J et al. Cross-disorder analysis of schizophrenia and 19 immune-mediated diseases identifies shared genetic risk. Human Molecular Genetics. 2019 Oct 15;28(20):3498-3513. Epub 2019 Jun 18. doi: 10.1093/hmg/ddz145

Author

Pouget, Jennie G ; Han, Buhm ; Wu, Yang et al. / Cross-disorder analysis of schizophrenia and 19 immune-mediated diseases identifies shared genetic risk. In: Human Molecular Genetics. 2019 ; Vol. 28, No. 20. pp. 3498-3513.

Bibtex

@article{b883d511f13d41f9862ad658b42f90a0,
title = "Cross-disorder analysis of schizophrenia and 19 immune-mediated diseases identifies shared genetic risk",
abstract = "Many immune diseases occur at different rates among people with schizophrenia compared to the general population. Here, we evaluated whether this phenomenon might be explained by shared genetic risk factors. We used data from large genome-wide association studies to compare the genetic architecture of schizophrenia to 19 immune diseases. First, we evaluated the association with schizophrenia of 581 variants previously reported to be associated with immune diseases at genome-wide significance. We identified five variants with potentially pleiotropic effects. While colocalization analyses were inconclusive, functional characterization of these variants provided the strongest evidence for a model in which genetic variation at rs1734907 modulates risk of schizophrenia and Crohn's disease via altered methylation and expression of EPHB4-a gene whose protein product guides the migration of neuronal axons in the brain and the migration of lymphocytes towards infected cells in the immune system. Next, we investigated genome-wide sharing of common variants between schizophrenia and immune diseases using cross-trait LD score regression. Of the 11 immune diseases with available genome-wide summary statistics, we observed genetic correlation between six immune diseases and schizophrenia: inflammatory bowel disease (rg = 0.12 ± 0.03, P = 2.49 × 10-4), Crohn's disease (rg = 0.097 ± 0.06, P = 3.27 × 10-3), ulcerative colitis (rg = 0.11 ± 0.04, P = 4.05 × 10-3), primary biliary cirrhosis (rg = 0.13 ± 0.05, P = 3.98 × 10-3), psoriasis (rg = 0.18 ± 0.07, P = 7.78 × 10-3) and systemic lupus erythematosus (rg = 0.13 ± 0.05, P = 3.76 × 10-3). With the exception of ulcerative colitis, the degree and direction of these genetic correlations were consistent with the expected phenotypic correlation based on epidemiological data. Our findings suggest shared genetic risk factors contribute to the epidemiological association of certain immune diseases and schizophrenia.",
author = "Pouget, {Jennie G} and Buhm Han and Yang Wu and Emmanuel Mignot and Ollila, {Hanna M} and Jonathan Barker and Sarah Spain and Nick Dand and Richard Trembath and Javier Martin and Mayes, {Maureen D} and Lara Bossini-Castillo and Elena L{\'o}pez-Isac and Ying Jin and Santorico, {Stephanie A} and Spritz, {Richard A} and Hakon Hakonarson and Constantin Polychronakos and Soumya Raychaudhuri and Jo Knight and {Schizophrenia Working Group of the Psychiatric Genomics Consortium}",
note = "{\textcopyright} The Author(s) 2019. Published by Oxford University Press.",
year = "2019",
month = oct,
day = "15",
doi = "10.1093/hmg/ddz145",
language = "English",
volume = "28",
pages = "3498--3513",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "20",

}

RIS

TY - JOUR

T1 - Cross-disorder analysis of schizophrenia and 19 immune-mediated diseases identifies shared genetic risk

AU - Pouget, Jennie G

AU - Han, Buhm

AU - Wu, Yang

AU - Mignot, Emmanuel

AU - Ollila, Hanna M

AU - Barker, Jonathan

AU - Spain, Sarah

AU - Dand, Nick

AU - Trembath, Richard

AU - Martin, Javier

AU - Mayes, Maureen D

AU - Bossini-Castillo, Lara

AU - López-Isac, Elena

AU - Jin, Ying

AU - Santorico, Stephanie A

AU - Spritz, Richard A

AU - Hakonarson, Hakon

AU - Polychronakos, Constantin

AU - Raychaudhuri, Soumya

AU - Knight, Jo

AU - Schizophrenia Working Group of the Psychiatric Genomics Consortium

N1 - © The Author(s) 2019. Published by Oxford University Press.

PY - 2019/10/15

Y1 - 2019/10/15

N2 - Many immune diseases occur at different rates among people with schizophrenia compared to the general population. Here, we evaluated whether this phenomenon might be explained by shared genetic risk factors. We used data from large genome-wide association studies to compare the genetic architecture of schizophrenia to 19 immune diseases. First, we evaluated the association with schizophrenia of 581 variants previously reported to be associated with immune diseases at genome-wide significance. We identified five variants with potentially pleiotropic effects. While colocalization analyses were inconclusive, functional characterization of these variants provided the strongest evidence for a model in which genetic variation at rs1734907 modulates risk of schizophrenia and Crohn's disease via altered methylation and expression of EPHB4-a gene whose protein product guides the migration of neuronal axons in the brain and the migration of lymphocytes towards infected cells in the immune system. Next, we investigated genome-wide sharing of common variants between schizophrenia and immune diseases using cross-trait LD score regression. Of the 11 immune diseases with available genome-wide summary statistics, we observed genetic correlation between six immune diseases and schizophrenia: inflammatory bowel disease (rg = 0.12 ± 0.03, P = 2.49 × 10-4), Crohn's disease (rg = 0.097 ± 0.06, P = 3.27 × 10-3), ulcerative colitis (rg = 0.11 ± 0.04, P = 4.05 × 10-3), primary biliary cirrhosis (rg = 0.13 ± 0.05, P = 3.98 × 10-3), psoriasis (rg = 0.18 ± 0.07, P = 7.78 × 10-3) and systemic lupus erythematosus (rg = 0.13 ± 0.05, P = 3.76 × 10-3). With the exception of ulcerative colitis, the degree and direction of these genetic correlations were consistent with the expected phenotypic correlation based on epidemiological data. Our findings suggest shared genetic risk factors contribute to the epidemiological association of certain immune diseases and schizophrenia.

AB - Many immune diseases occur at different rates among people with schizophrenia compared to the general population. Here, we evaluated whether this phenomenon might be explained by shared genetic risk factors. We used data from large genome-wide association studies to compare the genetic architecture of schizophrenia to 19 immune diseases. First, we evaluated the association with schizophrenia of 581 variants previously reported to be associated with immune diseases at genome-wide significance. We identified five variants with potentially pleiotropic effects. While colocalization analyses were inconclusive, functional characterization of these variants provided the strongest evidence for a model in which genetic variation at rs1734907 modulates risk of schizophrenia and Crohn's disease via altered methylation and expression of EPHB4-a gene whose protein product guides the migration of neuronal axons in the brain and the migration of lymphocytes towards infected cells in the immune system. Next, we investigated genome-wide sharing of common variants between schizophrenia and immune diseases using cross-trait LD score regression. Of the 11 immune diseases with available genome-wide summary statistics, we observed genetic correlation between six immune diseases and schizophrenia: inflammatory bowel disease (rg = 0.12 ± 0.03, P = 2.49 × 10-4), Crohn's disease (rg = 0.097 ± 0.06, P = 3.27 × 10-3), ulcerative colitis (rg = 0.11 ± 0.04, P = 4.05 × 10-3), primary biliary cirrhosis (rg = 0.13 ± 0.05, P = 3.98 × 10-3), psoriasis (rg = 0.18 ± 0.07, P = 7.78 × 10-3) and systemic lupus erythematosus (rg = 0.13 ± 0.05, P = 3.76 × 10-3). With the exception of ulcerative colitis, the degree and direction of these genetic correlations were consistent with the expected phenotypic correlation based on epidemiological data. Our findings suggest shared genetic risk factors contribute to the epidemiological association of certain immune diseases and schizophrenia.

U2 - 10.1093/hmg/ddz145

DO - 10.1093/hmg/ddz145

M3 - Journal article

C2 - 31211845

VL - 28

SP - 3498

EP - 3513

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 20

ER -