GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study
Rongve, Arvid; Witoelar, Aree; Ruiz, Agustín; Athanasiu, Lavinia; Abdelnour, Carla; Clarimon, Jordi; Heilmann-Heimbach, Stefanie; Hernández, Isabel; Moreno-Grau, Sonia; de Rojas, Itziar; Morenas-Rodríguez, Estrella; Fladby, Tormod; Sando, Sigrid Botne; Bråthen, Geir; Blanc, Frédéric; Bousiges, Olivier; Lemstra, Afina W.; van Steenoven, Inger; Londos, Elisabet; Almdahl, Ina Selseth; Pålhaugen, Lene; Eriksen, Jon Alm; Djurovic, Srdjan; Stordal, Eystein; Saltvedt, Ingvild; Ulstein, Ingun; Bettella, Francesco; Desikan, Rahul S.; Idland, Ane-Victoria; Toft, Mathias; Pihlstrøm, Lasse; Snaedal, Jon; Tárraga, Lluís; Boada, Mercè; Lleó, Alberto; Stefánsson, Hreinn; Stefánsson, Kári; Ramírez, Alfredo; Aarsland, Dag; Andreassen, Ole Andreas
Peer reviewed, Journal article
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Dementia with Lewy Bodies (DLB) is a common neurodegenerative disorder with poor prognosis and mainly unknown pathophysiology. Heritability estimates exceed 30% but few genetic risk variants have been identified. Here we investigated common genetic variants associated with DLB in a large European multisite sample. We performed a genome wide association study in Norwegian and European cohorts of 720 DLB cases and 6490 controls and included 19 top-associated single-nucleotide polymorphisms in an additional cohort of 108 DLB cases and 75545 controls from Iceland. Overall the study included 828 DLB cases and 82035 controls. Variants in the ASH1L/GBA (Chr1q22) and APOE ε4 (Chr19) loci were associated with DLB surpassing the genome-wide significance threshold (p < 5 × 10−8). One additional genetic locus previously linked to psychosis in Alzheimer’s disease, ZFPM1 (Chr16q24.2), showed suggestive association with DLB at p-value < 1 × 10−6. We report two susceptibility loci for DLB at genome-wide significance, providing insight into etiological factors. These findings highlight the complex relationship between the genetic architecture of DLB and other neurodegenerative disorders.