Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants

Lam C. Tsoi; Philip E. Stuart; Chao Tian; Johann E. Gudjonsson; Sayantan Das; Matthew Zawistowski; Eva Ellinghaus; Jonathan N. Barker; Vinod Chandran; Nick Dand; Kristina Callis Duffin; Charlotta Enerbäck; Tõnu Esko; Andre Franke; Dafna D. Gladman; Per Hoffmann; Külli Kingo; Sulev Kõks; Gerald G. Krueger; Henry W. Lim; Andres Metspalu; Ulrich Mrowietz; Sören Mucha; Proton Rahman; Andre Reis; Trilokraj Tejasvi; Richard Trembath; John J. Voorhees; Stephan Weidinger; Michael Weichenthal; Xiaoquan Wen; Nicholas Eriksson; Hyun M. Kang; David A. Hinds; Rajan P. Nair; Gonçalo R. Abecasis; James T. Elder

doi:10.1038/ncomms15382

Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants

Lam C. Tsoi, Philip E. Stuart, Chao Tian, Johann E. Gudjonsson, Sayantan Das, Matthew Zawistowski, Eva Ellinghaus, Jonathan N. Barker, Vinod Chandran, Nick Dand, Kristina Callis Duffin, Charlotta Enerbäck, Tõnu Esko, Andre Franke, Dafna D. Gladman, Per Hoffmann, Külli Kingo, Sulev Kõks, Gerald G. Krueger, Henry W. LimAndres Metspalu, Ulrich Mrowietz, Sören Mucha, Proton Rahman, Andre Reis, Trilokraj Tejasvi, Richard Trembath, John J. Voorhees, Stephan Weidinger, Michael Weichenthal, Xiaoquan Wen, Nicholas Eriksson, Hyun M. Kang, David A. Hinds, Rajan P. Nair, Gonçalo R. Abecasis, James T. Elder^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Psoriasis is a complex disease of skin with a prevalence of about 2%. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for psoriasis to date, including data from eight different Caucasian cohorts, with a combined effective sample size >39,000 individuals. We identified 16 additional psoriasis susceptibility loci achieving genome-wide significance, increasing the number of identified loci to 63 for European-origin individuals. Functional analysis highlighted the roles of interferon signalling and the NF B cascade, and we showed that the psoriasis signals are enriched in regulatory elements from different T cells (CD8 + T-cells and CD4 + T-cells including T H 0, T H 1 and T H 17). The identified loci explain â 1/428% of the genetic heritability and generate a discriminatory genetic risk score (AUC=0.76 in our sample) that is significantly correlated with age at onset (p=2 × 10 â '89). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis.

Original language	English
Article number	15382
Journal	Nature Communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms15382
Publication status	Published - 24 May 2017

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Tsoi, L. C., Stuart, P. E., Tian, C., Gudjonsson, J. E., Das, S., Zawistowski, M., Ellinghaus, E., Barker, J. N., Chandran, V., Dand, N., Duffin, K. C., Enerbäck, C., Esko, T., Franke, A., Gladman, D. D., Hoffmann, P., Kingo, K., Kõks, S., Krueger, G. G., ... Elder, J. T. (2017). Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants. Nature Communications, 8, Article 15382. https://doi.org/10.1038/ncomms15382

@article{d35fe5e74cb0451e95c27d0eb84901c7,

title = "Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants",

abstract = "Psoriasis is a complex disease of skin with a prevalence of about 2%. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for psoriasis to date, including data from eight different Caucasian cohorts, with a combined effective sample size >39,000 individuals. We identified 16 additional psoriasis susceptibility loci achieving genome-wide significance, increasing the number of identified loci to 63 for European-origin individuals. Functional analysis highlighted the roles of interferon signalling and the NF B cascade, and we showed that the psoriasis signals are enriched in regulatory elements from different T cells (CD8 + T-cells and CD4 + T-cells including T H 0, T H 1 and T H 17). The identified loci explain {\^a} 1/428% of the genetic heritability and generate a discriminatory genetic risk score (AUC=0.76 in our sample) that is significantly correlated with age at onset (p=2 × 10 {\^a} '89). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis.",

author = "Tsoi, {Lam C.} and Stuart, {Philip E.} and Chao Tian and Gudjonsson, {Johann E.} and Sayantan Das and Matthew Zawistowski and Eva Ellinghaus and Barker, {Jonathan N.} and Vinod Chandran and Nick Dand and Duffin, {Kristina Callis} and Charlotta Enerb{\"a}ck and T{\~o}nu Esko and Andre Franke and Gladman, {Dafna D.} and Per Hoffmann and K{\"u}lli Kingo and Sulev K{\~o}ks and Krueger, {Gerald G.} and Lim, {Henry W.} and Andres Metspalu and Ulrich Mrowietz and S{\"o}ren Mucha and Proton Rahman and Andre Reis and Trilokraj Tejasvi and Richard Trembath and Voorhees, {John J.} and Stephan Weidinger and Michael Weichenthal and Xiaoquan Wen and Nicholas Eriksson and Kang, {Hyun M.} and Hinds, {David A.} and Nair, {Rajan P.} and Abecasis, {Gon{\c c}alo R.} and Elder, {James T.}",

year = "2017",

month = may,

day = "24",

doi = "10.1038/ncomms15382",

language = "English",

volume = "8",

journal = "Nature Communications",

issn = "2041-1723",

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Tsoi, LC, Stuart, PE, Tian, C, Gudjonsson, JE, Das, S, Zawistowski, M, Ellinghaus, E, Barker, JN, Chandran, V, Dand, N, Duffin, KC, Enerbäck, C, Esko, T, Franke, A, Gladman, DD, Hoffmann, P, Kingo, K, Kõks, S, Krueger, GG, Lim, HW, Metspalu, A, Mrowietz, U, Mucha, S, Rahman, P, Reis, A, Tejasvi, T, Trembath, R, Voorhees, JJ, Weidinger, S, Weichenthal, M, Wen, X, Eriksson, N, Kang, HM, Hinds, DA, Nair, RP, Abecasis, GR & Elder, JT 2017, 'Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants', Nature Communications, vol. 8, 15382. https://doi.org/10.1038/ncomms15382

TY - JOUR

T1 - Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants

AU - Tsoi, Lam C.

AU - Stuart, Philip E.

AU - Tian, Chao

AU - Gudjonsson, Johann E.

AU - Das, Sayantan

AU - Zawistowski, Matthew

AU - Ellinghaus, Eva

AU - Barker, Jonathan N.

AU - Chandran, Vinod

AU - Dand, Nick

AU - Duffin, Kristina Callis

AU - Enerbäck, Charlotta

AU - Esko, Tõnu

AU - Franke, Andre

AU - Gladman, Dafna D.

AU - Hoffmann, Per

AU - Kingo, Külli

AU - Kõks, Sulev

AU - Krueger, Gerald G.

AU - Lim, Henry W.

AU - Metspalu, Andres

AU - Mrowietz, Ulrich

AU - Mucha, Sören

AU - Rahman, Proton

AU - Reis, Andre

AU - Tejasvi, Trilokraj

AU - Trembath, Richard

AU - Voorhees, John J.

AU - Weidinger, Stephan

AU - Weichenthal, Michael

AU - Wen, Xiaoquan

AU - Eriksson, Nicholas

AU - Kang, Hyun M.

AU - Hinds, David A.

AU - Nair, Rajan P.

AU - Abecasis, Gonçalo R.

AU - Elder, James T.

PY - 2017/5/24

Y1 - 2017/5/24

N2 - Psoriasis is a complex disease of skin with a prevalence of about 2%. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for psoriasis to date, including data from eight different Caucasian cohorts, with a combined effective sample size >39,000 individuals. We identified 16 additional psoriasis susceptibility loci achieving genome-wide significance, increasing the number of identified loci to 63 for European-origin individuals. Functional analysis highlighted the roles of interferon signalling and the NF B cascade, and we showed that the psoriasis signals are enriched in regulatory elements from different T cells (CD8 + T-cells and CD4 + T-cells including T H 0, T H 1 and T H 17). The identified loci explain â 1/428% of the genetic heritability and generate a discriminatory genetic risk score (AUC=0.76 in our sample) that is significantly correlated with age at onset (p=2 × 10 â '89). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis.

AB - Psoriasis is a complex disease of skin with a prevalence of about 2%. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for psoriasis to date, including data from eight different Caucasian cohorts, with a combined effective sample size >39,000 individuals. We identified 16 additional psoriasis susceptibility loci achieving genome-wide significance, increasing the number of identified loci to 63 for European-origin individuals. Functional analysis highlighted the roles of interferon signalling and the NF B cascade, and we showed that the psoriasis signals are enriched in regulatory elements from different T cells (CD8 + T-cells and CD4 + T-cells including T H 0, T H 1 and T H 17). The identified loci explain â 1/428% of the genetic heritability and generate a discriminatory genetic risk score (AUC=0.76 in our sample) that is significantly correlated with age at onset (p=2 × 10 â '89). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis.

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U2 - 10.1038/ncomms15382

DO - 10.1038/ncomms15382

M3 - Article

AN - SCOPUS:85019965749

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

M1 - 15382

ER -

Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants

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