Institut for Biomedicin

Preben Bo Mortensen

Gene expression imputation across multiple brain regions provides insights into schizophrenia risk

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Standard

Gene expression imputation across multiple brain regions provides insights into schizophrenia risk. / Huckins, Laura M; Dobbyn, Amanda; Ruderfer, Douglas M; Hoffman, Gabriel; Wang, Weiqing; Pardiñas, Antonio F; Rajagopal, Veera M; Als, Thomas D; T Nguyen, Hoang; Girdhar, Kiran; Boocock, James; Roussos, Panos; Fromer, Menachem; Kramer, Robin; Domenici, Enrico; Gamazon, Eric R; Purcell, Shaun; Demontis, Ditte; Børglum, Anders D; Walters, James T R; O'Donovan, Michael C; Sullivan, Patrick; Owen, Michael J; Devlin, Bernie; Sieberts, Solveig K; Cox, Nancy J; Im, Hae Kyung; Sklar, Pamela; Stahl, Eli A; CommonMind Consortium; The Schizophrenia Working Group of the Psychiatric Genomics Consortium; iPSYCH-GEMS Schizophrenia Working Group.

I: Nature Genetics, Bind 51, Nr. 4, 04.2019, s. 659-674.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Huckins, LM, Dobbyn, A, Ruderfer, DM, Hoffman, G, Wang, W, Pardiñas, AF, Rajagopal, VM, Als, TD, T Nguyen, H, Girdhar, K, Boocock, J, Roussos, P, Fromer, M, Kramer, R, Domenici, E, Gamazon, ER, Purcell, S, Demontis, D, Børglum, AD, Walters, JTR, O'Donovan, MC, Sullivan, P, Owen, MJ, Devlin, B, Sieberts, SK, Cox, NJ, Im, HK, Sklar, P, Stahl, EA, CommonMind Consortium, The Schizophrenia Working Group of the Psychiatric Genomics Consortium & iPSYCH-GEMS Schizophrenia Working Group 2019, 'Gene expression imputation across multiple brain regions provides insights into schizophrenia risk', Nature Genetics, bind 51, nr. 4, s. 659-674. https://doi.org/10.1038/s41588-019-0364-4

APA

Huckins, L. M., Dobbyn, A., Ruderfer, D. M., Hoffman, G., Wang, W., Pardiñas, A. F., Rajagopal, V. M., Als, T. D., T Nguyen, H., Girdhar, K., Boocock, J., Roussos, P., Fromer, M., Kramer, R., Domenici, E., Gamazon, E. R., Purcell, S., Demontis, D., Børglum, A. D., ... iPSYCH-GEMS Schizophrenia Working Group (2019). Gene expression imputation across multiple brain regions provides insights into schizophrenia risk. Nature Genetics, 51(4), 659-674. https://doi.org/10.1038/s41588-019-0364-4

CBE

Huckins LM, Dobbyn A, Ruderfer DM, Hoffman G, Wang W, Pardiñas AF, Rajagopal VM, Als TD, T Nguyen H, Girdhar K, Boocock J, Roussos P, Fromer M, Kramer R, Domenici E, Gamazon ER, Purcell S, Demontis D, Børglum AD, Walters JTR, O'Donovan MC, Sullivan P, Owen MJ, Devlin B, Sieberts SK, Cox NJ, Im HK, Sklar P, Stahl EA, CommonMind Consortium, The Schizophrenia Working Group of the Psychiatric Genomics Consortium, iPSYCH-GEMS Schizophrenia Working Group. 2019. Gene expression imputation across multiple brain regions provides insights into schizophrenia risk. Nature Genetics. 51(4):659-674. https://doi.org/10.1038/s41588-019-0364-4

MLA

Vancouver

Huckins LM, Dobbyn A, Ruderfer DM, Hoffman G, Wang W, Pardiñas AF o.a. Gene expression imputation across multiple brain regions provides insights into schizophrenia risk. Nature Genetics. 2019 apr;51(4):659-674. https://doi.org/10.1038/s41588-019-0364-4

Author

Huckins, Laura M ; Dobbyn, Amanda ; Ruderfer, Douglas M ; Hoffman, Gabriel ; Wang, Weiqing ; Pardiñas, Antonio F ; Rajagopal, Veera M ; Als, Thomas D ; T Nguyen, Hoang ; Girdhar, Kiran ; Boocock, James ; Roussos, Panos ; Fromer, Menachem ; Kramer, Robin ; Domenici, Enrico ; Gamazon, Eric R ; Purcell, Shaun ; Demontis, Ditte ; Børglum, Anders D ; Walters, James T R ; O'Donovan, Michael C ; Sullivan, Patrick ; Owen, Michael J ; Devlin, Bernie ; Sieberts, Solveig K ; Cox, Nancy J ; Im, Hae Kyung ; Sklar, Pamela ; Stahl, Eli A ; CommonMind Consortium ; The Schizophrenia Working Group of the Psychiatric Genomics Consortium ; iPSYCH-GEMS Schizophrenia Working Group. / Gene expression imputation across multiple brain regions provides insights into schizophrenia risk. I: Nature Genetics. 2019 ; Bind 51, Nr. 4. s. 659-674.

Bibtex

@article{583c76f7189b4a499ac7d631c7975454,
title = "Gene expression imputation across multiple brain regions provides insights into schizophrenia risk",
abstract = "Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.",
keywords = "Brain/physiopathology, Case-Control Studies, Gene Expression/genetics, Genetic Predisposition to Disease, Genome-Wide Association Study/methods, Genotype, Humans, Polymorphism, Single Nucleotide/genetics, Quantitative Trait Loci/genetics, Risk, Schizophrenia/genetics, Transcriptome/genetics, ACUTE INTERMITTENT PORPHYRIA, TRANSCRIPTOME, VARIANTS, MOUSE, CHILDHOOD, PSYCHOSIS, DISORDER, TRAITS, ASSOCIATION, COGNITIVE DEFICITS",
author = "Huckins, {Laura M} and Amanda Dobbyn and Ruderfer, {Douglas M} and Gabriel Hoffman and Weiqing Wang and Pardi{\~n}as, {Antonio F} and Rajagopal, {Veera M} and Als, {Thomas D} and {T Nguyen}, Hoang and Kiran Girdhar and James Boocock and Panos Roussos and Menachem Fromer and Robin Kramer and Enrico Domenici and Gamazon, {Eric R} and Shaun Purcell and Ditte Demontis and B{\o}rglum, {Anders D} and Walters, {James T R} and O'Donovan, {Michael C} and Patrick Sullivan and Owen, {Michael J} and Bernie Devlin and Sieberts, {Solveig K} and Cox, {Nancy J} and Im, {Hae Kyung} and Pamela Sklar and Stahl, {Eli A} and Mortensen, {Preben Bo} and {CommonMind Consortium} and {The Schizophrenia Working Group of the Psychiatric Genomics Consortium} and {iPSYCH-GEMS Schizophrenia Working Group}",
year = "2019",
month = apr,
doi = "10.1038/s41588-019-0364-4",
language = "English",
volume = "51",
pages = "659--674",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "4",

}

RIS

TY - JOUR

T1 - Gene expression imputation across multiple brain regions provides insights into schizophrenia risk

AU - Huckins, Laura M

AU - Dobbyn, Amanda

AU - Ruderfer, Douglas M

AU - Hoffman, Gabriel

AU - Wang, Weiqing

AU - Pardiñas, Antonio F

AU - Rajagopal, Veera M

AU - Als, Thomas D

AU - T Nguyen, Hoang

AU - Girdhar, Kiran

AU - Boocock, James

AU - Roussos, Panos

AU - Fromer, Menachem

AU - Kramer, Robin

AU - Domenici, Enrico

AU - Gamazon, Eric R

AU - Purcell, Shaun

AU - Demontis, Ditte

AU - Børglum, Anders D

AU - Walters, James T R

AU - O'Donovan, Michael C

AU - Sullivan, Patrick

AU - Owen, Michael J

AU - Devlin, Bernie

AU - Sieberts, Solveig K

AU - Cox, Nancy J

AU - Im, Hae Kyung

AU - Sklar, Pamela

AU - Stahl, Eli A

AU - Mortensen, Preben Bo

AU - CommonMind Consortium

AU - The Schizophrenia Working Group of the Psychiatric Genomics Consortium

AU - iPSYCH-GEMS Schizophrenia Working Group

PY - 2019/4

Y1 - 2019/4

N2 - Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.

AB - Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.

KW - Brain/physiopathology

KW - Case-Control Studies

KW - Gene Expression/genetics

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study/methods

KW - Genotype

KW - Humans

KW - Polymorphism, Single Nucleotide/genetics

KW - Quantitative Trait Loci/genetics

KW - Risk

KW - Schizophrenia/genetics

KW - Transcriptome/genetics

KW - ACUTE INTERMITTENT PORPHYRIA

KW - TRANSCRIPTOME

KW - VARIANTS

KW - MOUSE

KW - CHILDHOOD

KW - PSYCHOSIS

KW - DISORDER

KW - TRAITS

KW - ASSOCIATION

KW - COGNITIVE DEFICITS

U2 - 10.1038/s41588-019-0364-4

DO - 10.1038/s41588-019-0364-4

M3 - Journal article

C2 - 30911161

VL - 51

SP - 659

EP - 674

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 4

ER -