|Title:||Identification of susceptible loci and enriched pathways for Bipolar II disorder using genome-wide association studies||Authors:||Kao C.-F.
|Issue Date:||2016||Journal Volume:||19||Journal Issue:||12||Source:||International Journal of Neuropsychopharmacology||Abstract:||
Background: This study aimed to identify susceptible loci and enriched pathways for bipolar disorder subtype II. Methods: We conducted a genome-wide association scan in discovery samples with 189 bipolar disorder subtype II patients and 1773 controls, and replication samples with 283 bipolar disorder subtype II patients and 500 controls in a Taiwanese Han population using Affymetrix Axiom Genome-Wide CHB1 Array. We performed single-marker and gene-based association analyses, as well as calculated polygeneic risk scores for bipolar disorder subtype II. Pathway enrichment analyses were employed to reveal significant biological pathways. Results: Seven markers were found to be associated with bipolar disorder subtype II in meta-analysis combining both discovery and replication samples (P < 5.0 × 10-6), including markers in or close to MYO16, HSP90AB3P, noncoding gene LOC100507632, and markers in chromosomes 4 and 10. A novel locus, ETF1, was associated with bipolar disorder subtype II (P < 6.0 × 10-3) in gene-based association tests. Results of risk evaluation demonstrated that higher genetic risk scores were able to distinguish bipolar disorder subtype II patients from healthy controls in both discovery (P = 3.9 × 10-4 ?1.0 × 10-3) and replication samples (2.8 × 10-4 ?1.7 × 10-3). Genetic variance explained by chip markers for bipolar disorder subtype II was substantial in the discovery (55.1%) and replication (60.5%) samples. Moreover, pathways related to neurodevelopmental function, signal transduction, neuronal system, and cell adhesion molecules were significantly associated with bipolar disorder subtype II. Conclusion: We reported novel susceptible loci for pure bipolar subtype II disorder that is less addressed in the literature. Future studies are needed to confirm the roles of these loci for bipolar disorder subtype II. ? The Author 2016.
|ISSN:||14611457||DOI:||10.1093/ijnppy/pyw064||SDG/Keyword:||cell adhesion molecule; genomic DNA; AL355490.1 gene; Article; bipolar II disorder; CDKL4 gene; chromosome 10; chromosome 4; controlled study; DNA extraction; ETF1 gene; gene; gene locus; gene mapping; genetic risk; genetic susceptibility; genetic variability; genome-wide association study; genotyping technique; heritability; human; IWS1 gene; KCNAB2 gene; major clinical study; MAP4K3 gene; nerve cell differentiation; PJA2 gene; priority journal; risk assessment; RRP12 gene; signal transduction; TLL2 gene; VSIG10 gene; adolescent; adult; aged; bipolar disorder; case control study; DNA microarray; female; gene expression profiling; gene frequency; gene locus; gene regulatory network; genetic marker; genetic predisposition; genetics; heredity; male; middle aged; multifactorial inheritance; phenotype; procedures; psychology; risk factor; single nucleotide polymorphism; Taiwan; young adult; Adolescent; Adult; Aged; Bipolar Disorder; Case-Control Studies; Female; Gene Expression Profiling; Gene Frequency; Gene Regulatory Networks; Genetic Loci; Genetic Markers; Genetic Predisposition to Disease; Genome-Wide Association Study; Heredity; Humans; Male; Middle Aged; Multifactorial Inheritance; Oligonucleotide Array Sequence Analysis; Phenotype; Polymorphism, Single Nucleotide; Risk Assessment; Risk Factors; Taiwan; Young Adult
|Appears in Collections:||醫學院附設醫院 (臺大醫院)|
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