Genome-wide burden of deleterious coding variants increased in schizophrenia

Loes M.Olde Loohuis; Jacob A.S. Vorstman; Anil P. Ori; Kim A. Staats; Tina Wang; Alexander L. Richards; Ganna Leonenko; James T. Walters; Joseph Deyoung; Rita M. Cantor; Roel A. Ophoff; René S. Kahn; Don Linszen; Jim Van Os; Durk Wiersma; Richard Bruggeman; Wiepke Cahn; Lieuwe De Haan; Lydia Krabbendam; Inez Myin-Germeys

doi:10.1038/ncomms8501

Genome-wide burden of deleterious coding variants increased in schizophrenia

Loes M.Olde Loohuis, Jacob A.S. Vorstman, Anil P. Ori, Kim A. Staats, Tina Wang, Alexander L. Richards, Ganna Leonenko, James T. Walters, Joseph Deyoung, Rita M. Cantor, Roel A. Ophoff, René S. Kahn, Don Linszen, Jim Van Os, Durk Wiersma, Richard Bruggeman, Wiepke Cahn, Lieuwe De Haan, Lydia Krabbendam, Inez Myin-Germeys

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21 Scopus citations

Abstract

Schizophrenia is a common complex disorder with polygenic inheritance. Here we show that by using an approach that compares the individual loads of rare variants in 1,042 schizophrenia cases and 961 controls, schizophrenia cases carry an increased burden of deleterious mutations. At a genome-wide level, our results implicate non-synonymous, splice site as well as stop-altering single-nucleotide variations occurring at minor allele frequency of ≥ 0.01% in the population. In an independent replication sample of 5,585 schizophrenia cases and 8,103 controls of European ancestry we confirm an enrichment in cases of the alleles identified in our study. In addition, the genes implicated by the increased burden of rare coding variants highlight the involvement of neurodevelopment in the aetiology of schizophrenia.

Original language	English
Article number	7501
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8501
State	Published - 9 Jul 2015
Externally published	Yes

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Loohuis, L. M. O., Vorstman, J. A. S., Ori, A. P., Staats, K. A., Wang, T., Richards, A. L., Leonenko, G., Walters, J. T., Deyoung, J., Cantor, R. M., Ophoff, R. A., Kahn, R. S., Linszen, D., Van Os, J., Wiersma, D., Bruggeman, R., Cahn, W., De Haan, L., Krabbendam, L., & Myin-Germeys, I. (2015). Genome-wide burden of deleterious coding variants increased in schizophrenia. Nature Communications, 6, Article 7501. https://doi.org/10.1038/ncomms8501

@article{69b8c70237bd4d2f92e1e85ca036e33c,

title = "Genome-wide burden of deleterious coding variants increased in schizophrenia",

abstract = "Schizophrenia is a common complex disorder with polygenic inheritance. Here we show that by using an approach that compares the individual loads of rare variants in 1,042 schizophrenia cases and 961 controls, schizophrenia cases carry an increased burden of deleterious mutations. At a genome-wide level, our results implicate non-synonymous, splice site as well as stop-altering single-nucleotide variations occurring at minor allele frequency of ≥ 0.01% in the population. In an independent replication sample of 5,585 schizophrenia cases and 8,103 controls of European ancestry we confirm an enrichment in cases of the alleles identified in our study. In addition, the genes implicated by the increased burden of rare coding variants highlight the involvement of neurodevelopment in the aetiology of schizophrenia.",

author = "Loohuis, {Loes M.Olde} and Vorstman, {Jacob A.S.} and Ori, {Anil P.} and Staats, {Kim A.} and Tina Wang and Richards, {Alexander L.} and Ganna Leonenko and Walters, {James T.} and Joseph Deyoung and Cantor, {Rita M.} and Ophoff, {Roel A.} and Kahn, {Ren{\'e} S.} and Don Linszen and {Van Os}, Jim and Durk Wiersma and Richard Bruggeman and Wiepke Cahn and {De Haan}, Lieuwe and Lydia Krabbendam and Inez Myin-Germeys",

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month = jul,

day = "9",

doi = "10.1038/ncomms8501",

language = "English",

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Loohuis, LMO, Vorstman, JAS, Ori, AP, Staats, KA, Wang, T, Richards, AL, Leonenko, G, Walters, JT, Deyoung, J, Cantor, RM, Ophoff, RA, Kahn, RS, Linszen, D, Van Os, J, Wiersma, D, Bruggeman, R, Cahn, W, De Haan, L, Krabbendam, L & Myin-Germeys, I 2015, 'Genome-wide burden of deleterious coding variants increased in schizophrenia', Nature Communications, vol. 6, 7501. https://doi.org/10.1038/ncomms8501

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AU - Loohuis, Loes M.Olde

AU - Vorstman, Jacob A.S.

AU - Ori, Anil P.

AU - Staats, Kim A.

AU - Wang, Tina

AU - Richards, Alexander L.

AU - Leonenko, Ganna

AU - Walters, James T.

AU - Deyoung, Joseph

AU - Cantor, Rita M.

AU - Ophoff, Roel A.

AU - Kahn, René S.

AU - Linszen, Don

AU - Van Os, Jim

AU - Wiersma, Durk

AU - Bruggeman, Richard

AU - Cahn, Wiepke

AU - De Haan, Lieuwe

AU - Krabbendam, Lydia

AU - Myin-Germeys, Inez

PY - 2015/7/9

Y1 - 2015/7/9

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AB - Schizophrenia is a common complex disorder with polygenic inheritance. Here we show that by using an approach that compares the individual loads of rare variants in 1,042 schizophrenia cases and 961 controls, schizophrenia cases carry an increased burden of deleterious mutations. At a genome-wide level, our results implicate non-synonymous, splice site as well as stop-altering single-nucleotide variations occurring at minor allele frequency of ≥ 0.01% in the population. In an independent replication sample of 5,585 schizophrenia cases and 8,103 controls of European ancestry we confirm an enrichment in cases of the alleles identified in our study. In addition, the genes implicated by the increased burden of rare coding variants highlight the involvement of neurodevelopment in the aetiology of schizophrenia.

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SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

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Genome-wide burden of deleterious coding variants increased in schizophrenia

Abstract

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