Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

groep; 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; Andre G. Uitterlinden; Fernando Rivadeneira; Albert Hofman; Lyudmila Georgieva; Tao Li; Danielle Posthuma

doi:10.1038/ncomms14774

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

groep, 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, Andre G. Uitterlinden, Fernando Rivadeneira, Albert Hofman, Lyudmila GeorgievaTao Li, Danielle Posthuma

^*Corresponding author for this work

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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.

Original language	English
Article number	14774
Journal	Nature Communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms14774
Publication status	Published - 21 Mar 2017

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© 2017 The Author(s).

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groep, 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., Uitterlinden, A. G., Rivadeneira, F., Hofman, A., ... Posthuma, D. (2017). Genetic correlation between amyotrophic lateral sclerosis and schizophrenia. Nature Communications, 8, Article 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 = "groep and 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 Shuna Colville and Robert Swingler and Uitterlinden, {Andre G.} and Fernando Rivadeneira and Albert Hofman and Lyudmila Georgieva and Tao Li and Danielle Posthuma",

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

month = mar,

day = "21",

doi = "10.1038/ncomms14774",

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groep, 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, Uitterlinden, AG , Rivadeneira, F , Hofman, A, Georgieva, L, Li, T & Posthuma, D 2017, 'Genetic correlation between amyotrophic lateral sclerosis and schizophrenia', Nature Communications, vol. 8, 14774. https://doi.org/10.1038/ncomms14774

TY - JOUR

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AU - groep

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 - Colville, Shuna

AU - Swingler, Robert

AU - Uitterlinden, Andre G.

AU - Rivadeneira, Fernando

AU - Hofman, Albert

AU - Georgieva, Lyudmila

AU - Li, Tao

AU - Posthuma, Danielle

PY - 2017/3/21

Y1 - 2017/3/21

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.

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DO - 10.1038/ncomms14774

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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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