TY - JOUR
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 - AUTHOR GROUP
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, Stéphanie
AU - Salachas, François
AU - Meininger, Vincent
AU - de Carvalho, Mamede
AU - Pinto, Susana
AU - Mora, Jesus S.
AU - Rojas-García, Ricardo
AU - Polak, Meraida
AU - Chandran, Siddharthan
AU - Colville, Shuna
AU - Swingler, Robert
AU - Morrison, Karen E.
AU - Shaw, Pamela J.
AU - Hardy, John
AU - van der Kooi, Anneke J.
AU - Weber, Markus
AU - de Haan, Lieuwe
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 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 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 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 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 - https://doi.org/10.1038/ncomms14774
DO - https://doi.org/10.1038/ncomms14774
M3 - Article
C2 - 28322246
SN - 2041-1723
VL - 8
SP - 14774
JO - Nature communications
JF - Nature communications
ER -