TY - UNPB
T1 - The shared genetic risk architecture of neurological and psychiatric disorders
T2 - a genome-wide analysis
AU - Smeland, Olav B
AU - Kutrolli, Gleda
AU - Bahrami, Shahram
AU - Fominykh, Vera
AU - Parker, Nadine
AU - Hindley, Guy F L
AU - Rødevand, Linn
AU - Jaholkowski, Piotr
AU - Tesfaye, Markos
AU - Parekh, Pravesh
AU - Elvsåshagen, Torbjørn
AU - Grotzinger, Andrew D
AU - Steen, Nils Eiel
AU - van der Meer, Dennis
AU - O'Connell, Kevin S
AU - Djurovic, Srdjan
AU - Dale, Anders M
AU - Shadrin, Alexey A
AU - Frei, Oleksandr
AU - Andreassen, Ole A
AU - International Multiple Sclerosis Genetics Consortium (IMSGC)
AU - International Headache Genetics Consortium (IHGC)
PY - 2023/9/26
Y1 - 2023/9/26
N2 - While neurological and psychiatric disorders have historically been considered to reflect distinct pathogenic entities, recent findings suggest shared pathobiological mechanisms. However, the extent to which these heritable disorders share genetic influences remains unclear. Here, we performed a comprehensive analysis of GWAS data, involving nearly 1 million cases across ten neurological diseases and ten psychiatric disorders, to compare their common genetic risk and biological underpinnings. Using complementary statistical tools, we demonstrate widespread genetic overlap across the disorders, even in the absence of genetic correlations. This indicates that a large set of common variants impact risk of multiple neurological and psychiatric disorders, but with divergent effect sizes. Furthermore, biological interrogation revealed a range of biological processes associated with neurological diseases, while psychiatric disorders consistently implicated neuronal biology. Altogether, the study indicates that neurological and psychiatric disorders share key etiological aspects, which has important implications for disease classification, precision medicine, and clinical practice.
AB - While neurological and psychiatric disorders have historically been considered to reflect distinct pathogenic entities, recent findings suggest shared pathobiological mechanisms. However, the extent to which these heritable disorders share genetic influences remains unclear. Here, we performed a comprehensive analysis of GWAS data, involving nearly 1 million cases across ten neurological diseases and ten psychiatric disorders, to compare their common genetic risk and biological underpinnings. Using complementary statistical tools, we demonstrate widespread genetic overlap across the disorders, even in the absence of genetic correlations. This indicates that a large set of common variants impact risk of multiple neurological and psychiatric disorders, but with divergent effect sizes. Furthermore, biological interrogation revealed a range of biological processes associated with neurological diseases, while psychiatric disorders consistently implicated neuronal biology. Altogether, the study indicates that neurological and psychiatric disorders share key etiological aspects, which has important implications for disease classification, precision medicine, and clinical practice.
U2 - 10.1101/2023.07.21.23292993
DO - 10.1101/2023.07.21.23292993
M3 - Preprint
BT - The shared genetic risk architecture of neurological and psychiatric disorders
PB - MedRxiv
ER -