|Title:||Genetic loci associated with an earlier age at onset in multiplex schizophrenia||Authors:||Woolston A.L.
ERIC YAO-YU CHUANG
WEI J. CHEN
|Issue Date:||2017||Publisher:||Nature Publishing Group||Journal Volume:||7||Journal Issue:||1||Source:||Scientific Reports||Abstract:||
An earlier age at onset (AAO) has been associated with greater genetic loadings in schizophrenia. This study aimed to identify modifier loci associated with an earlier AAO of schizophrenia. A genome-wide association analysis (GWAS) was conducted in 94 schizophrenia probands with the earliest AAO and 91 with the latest AAO. Candidate single nucleotide polymorphisms (SNPs) were then genotyped in the co-affected siblings and unrelated probands. Multi-SNP genetic risk scores (GRS) composed of the candidate loci were used to distinguish patients with an early or late AAO. The 14-SNP GRS could distinguish the co-affected siblings (n = 90) of the earliest probands from those (n = 91) of the latest probands. When 132 patients with an earlier AAO and 158 patients with a later AAO were included, a significant trend in the 14-SNP GRS was detected among those unrelated probands from 4 family groups with the earliest, earlier, later, and latest AAO. The overall effect of the 14 SNPs on an AAO in schizophrenia was verified using co-affected siblings of the GWAS probands and trend effect across unrelated patients. Preliminary network analysis of these loci revealed the involvement of PARK2, a gene intensively reported in Parkinson's disease and schizophrenia research. © 2017 The Author(s).
|ISSN:||2045-2322||DOI:||10.1038/s41598-017-06795-8||SDG/Keyword:||adult; aged; case control study; female; gene locus; genetic marker; genetic predisposition; genetics; genome-wide association study; genotype; human; male; middle aged; onset age; schizophrenia; sibling; single nucleotide polymorphism; Adult; Age of Onset; Aged; Case-Control Studies; Female; Genetic Loci; Genetic Markers; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Schizophrenia; Siblings|
|Appears in Collections:||流行病學與預防醫學研究所|
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