Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

Russell L. McLaughlin; Dick Schijven; Wouter Van Rheenen; Kristel R. Van Eijk; Margaret O'Brien; René S. Kahn; Roel A. Ophoff; An Goris; Daniel G. Bradley; Ammar Al-Chalabi; Leonard H. Van Den Berg; Jurjen J. Luykx; Orla Hardiman; Jan H. Veldink; Aleksey Shatunov; Annelot M. Dekker; Frank P. Diekstra; Sara L. Pulit; Rick A.A. Van Der Spek; Perry T.C. Van Doormaal; William Sproviero; Ashley R. Jones; Garth A. Nicholson; Dominic B. Rowe; Roger Pamphlett; Matthew C. Kiernan; Denis Bauer; Tim Kahlke; Kelly Williams; Filip Eftimov; Isabella Fogh; Nicola Ticozzi; Kuang Lin; Stephanie Millecamps; Francois Salachas; Vincent Meininger; Mamede De Carvalho; Susana Pinto; Jesus S. Mora; Ricardo Rojas-Garcyá; Meraida Polak; Siddharthan Chandran; Peter M. Andersen; Tune H. Pers; Mark Hansen; Thomas Hansen; Tao Li; Line Olsen; Henrik B. Rasmussen; Thomas Werge; Project MinE GWAS Consortium & Schizophrenia Working Group of the Psychiatric Genomics Consortium

doi:10.1038/ncomms14774

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

Russell L. McLaughlin^*, Dick Schijven, Wouter Van Rheenen, Kristel R. Van Eijk, Margaret O'Brien, René S. Kahn, Roel A. Ophoff, An Goris, Daniel G. Bradley, Ammar Al-Chalabi, Leonard H. Van Den Berg, Jurjen J. Luykx, Orla Hardiman, Jan H. Veldink, Aleksey Shatunov, Annelot M. Dekker, Frank P. Diekstra, Sara L. Pulit, Rick A.A. Van Der Spek, Perry T.C. Van DoormaalWilliam Sproviero, Ashley R. Jones, Garth A. Nicholson, Dominic B. Rowe, Roger Pamphlett, Matthew C. Kiernan, Denis Bauer, Tim Kahlke, Kelly Williams, Filip Eftimov, Isabella Fogh, Nicola Ticozzi, Kuang Lin, Stephanie Millecamps, Francois Salachas, Vincent Meininger, Mamede De Carvalho, Susana Pinto, Jesus S. Mora, Ricardo Rojas-Garcyá, Meraida Polak, Siddharthan Chandran, Peter M. Andersen, Tune H. Pers, Mark Hansen, Thomas Hansen, Tao Li, Line Olsen, Henrik B. Rasmussen, Thomas Werge, Project MinE GWAS Consortium & Schizophrenia Working Group of the Psychiatric Genomics Consortium

^*Corresponding author af dette arbejde

Institut for Klinisk Medicin

61 Citationer (Scopus)

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Abstract

We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P=1 × 10^-4) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10^-7). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.

Originalsprog	Engelsk
Artikelnummer	14774
Tidsskrift	Nature Communications
Vol/bind	8
ISSN	2041-1723
DOI	https://doi.org/10.1038/ncomms14774
Status	Udgivet - 2017

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10.1038/ncomms14774Licens: CC BY

Genetic correlation between amyotrophic lateral sclerosis and schizophreniaForlagets udgivne version, 783 KBLicens: CC BY

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McLaughlin, R. L., Schijven, D., Van Rheenen, W., Van Eijk, K. R., O'Brien, M., Kahn, R. S., Ophoff, R. A., Goris, A., Bradley, D. G., Al-Chalabi, A., Van Den Berg, L. H., Luykx, J. J., Hardiman, O., Veldink, J. H., Shatunov, A., Dekker, A. M., Diekstra, F. P., Pulit, S. L., Van Der Spek, R. A. A., ... Project MinE GWAS Consortium & Schizophrenia Working Group of the Psychiatric Genomics Consortium (2017). Genetic correlation between amyotrophic lateral sclerosis and schizophrenia. Nature Communications, 8, Artikel 14774. https://doi.org/10.1038/ncomms14774

McLaughlin, RL, Schijven, D, Van Rheenen, W, Van Eijk, KR, O'Brien, M, Kahn, RS, Ophoff, RA, Goris, A, Bradley, DG, Al-Chalabi, A, Van Den Berg, LH, Luykx, JJ, Hardiman, O, Veldink, JH, Shatunov, A, Dekker, AM, Diekstra, FP, Pulit, SL, Van Der Spek, RAA, Van Doormaal, PTC, Sproviero, W, Jones, AR, Nicholson, GA, Rowe, DB, Pamphlett, R, Kiernan, MC, Bauer, D, Kahlke, T, Williams, K, Eftimov, F, Fogh, I, Ticozzi, N, Lin, K, Millecamps, S, Salachas, F, Meininger, V, Carvalho, MD, Pinto, S, Mora, JS, Rojas-Garcyá, R, Polak, M, Chandran, S, Andersen, PM, Pers, TH, Hansen, M, Hansen, T, Li, T, Olsen, L, Rasmussen, HB, Werge, T & Project MinE GWAS Consortium & Schizophrenia Working Group of the Psychiatric Genomics Consortium 2017, 'Genetic correlation between amyotrophic lateral sclerosis and schizophrenia', Nature Communications, bind 8, 14774. https://doi.org/10.1038/ncomms14774

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title = "Genetic correlation between amyotrophic lateral sclerosis and schizophrenia",

abstract = "We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P=1 × 10-4) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10-7). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.",

author = "McLaughlin, {Russell L.} and Dick Schijven and {Van Rheenen}, Wouter and {Van Eijk}, {Kristel R.} and Margaret O'Brien and Kahn, {Ren{\'e} S.} and Ophoff, {Roel A.} and An Goris and Bradley, {Daniel G.} and Ammar Al-Chalabi and {Van Den Berg}, {Leonard H.} and Luykx, {Jurjen J.} and Orla Hardiman and Veldink, {Jan H.} and Aleksey Shatunov and Dekker, {Annelot M.} and Diekstra, {Frank P.} and Pulit, {Sara L.} and {Van Der Spek}, {Rick A.A.} and {Van Doormaal}, {Perry T.C.} and William Sproviero and Jones, {Ashley R.} and Nicholson, {Garth A.} and Rowe, {Dominic B.} and Roger Pamphlett and Kiernan, {Matthew C.} and Denis Bauer and Tim Kahlke and Kelly Williams and Filip Eftimov and Isabella Fogh and Nicola Ticozzi and Kuang Lin and Stephanie Millecamps and Francois Salachas and Vincent Meininger and Carvalho, {Mamede De} and Susana Pinto and Mora, {Jesus S.} and Ricardo Rojas-Garcy{\'a} and Meraida Polak and Siddharthan Chandran and Andersen, {Peter M.} and Pers, {Tune H.} and Mark Hansen and Thomas Hansen and Tao Li and Line Olsen and Rasmussen, {Henrik B.} and Thomas Werge and {Project MinE GWAS Consortium & Schizophrenia Working Group of the Psychiatric Genomics Consortium}",

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T1 - Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

AU - McLaughlin, Russell L.

AU - Schijven, Dick

AU - Van Rheenen, Wouter

AU - Van Eijk, Kristel R.

AU - O'Brien, Margaret

AU - Kahn, René S.

AU - Ophoff, Roel A.

AU - Goris, An

AU - Bradley, Daniel G.

AU - Al-Chalabi, Ammar

AU - Van Den Berg, Leonard H.

AU - Luykx, Jurjen J.

AU - Hardiman, Orla

AU - Veldink, Jan H.

AU - Shatunov, Aleksey

AU - Dekker, Annelot M.

AU - Diekstra, Frank P.

AU - Pulit, Sara L.

AU - Van Der Spek, Rick A.A.

AU - Van Doormaal, Perry T.C.

AU - Sproviero, William

AU - Jones, Ashley R.

AU - Nicholson, Garth A.

AU - Rowe, Dominic B.

AU - Pamphlett, Roger

AU - Kiernan, Matthew C.

AU - Bauer, Denis

AU - Kahlke, Tim

AU - Williams, Kelly

AU - Eftimov, Filip

AU - Fogh, Isabella

AU - Ticozzi, Nicola

AU - Lin, Kuang

AU - Millecamps, Stephanie

AU - Salachas, Francois

AU - Meininger, Vincent

AU - Carvalho, Mamede De

AU - Pinto, Susana

AU - Mora, Jesus S.

AU - Rojas-Garcyá, Ricardo

AU - Polak, Meraida

AU - Chandran, Siddharthan

AU - Andersen, Peter M.

AU - Pers, Tune H.

AU - Hansen, Mark

AU - Hansen, Thomas

AU - Li, Tao

AU - Olsen, Line

AU - Rasmussen, Henrik B.

AU - Werge, Thomas

AU - Project MinE GWAS Consortium & Schizophrenia Working Group of the Psychiatric Genomics Consortium

PY - 2017

Y1 - 2017

N2 - We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P=1 × 10-4) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10-7). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.

AB - We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P=1 × 10-4) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10-7). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.

U2 - 10.1038/ncomms14774

DO - 10.1038/ncomms14774

M3 - Journal article

C2 - 28322246

AN - SCOPUS:85016060348

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

M1 - 14774

ER -

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

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