Study Report

Reference	Rajkumar, A. P., 2014 PMID: 25053281
Citation	Rajkumar, A. P., et al. (2014). "Analysis of t(9;17)(q33.2;q25.3) chromosomal breakpoint regions and genetic association reveals novel candidate genes for bipolar disorder." Bipolar Disord.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	family-based and case-control
Study Type	Candidate-gene association study
Sample Size	A family including four people; PGC BD: 7481 cases and 9250 controls; PGC SZ: 9394 cases and 12462 controls.
SNP/Region/Marker Size	PGC BD: 2415422 imputed SNPs; PGC SZ: 1252901 imputed SNPs
Predominant Ethnicity	Caucasian
Population	Danish, PGC BD and SZ data
Gender	the proband was a 60-year-old man
Age Group	adult : the proband was a 60-year-old man

Sample Diagnosis	ICD-10
Sample Status	The proband was a 60-year-old man (II:1) belonging to a family of European descent. He was interviewed using the Schedule for Clinical Assessment in Neuropsychiatry (SCAN). Two experienced psychiatrists used the SCAN interview and the proband's clinical notes to confirm the diagnosis as BD, current episode hypomanic and alcohol dependence syndrome, currently abstinent, in full remission (ICD-10 DCR: F31.0, F10.202). A review of his medical records revealed that the proband had been first diagnosed to have BD, at the age of 47 years, and that he had been first hospitalized for BD at the age of 50 years. The review confirmed that he had not suffered any non-psychiatric medical comorbidity, especially neurological and neurodevelopmental disorders.
Statistical Method	Genetic associations between all SNPs within the breakpoint regions and BD as well as SZ were calculated using the PGC BioQ application. Regional genetic association results were visualized using the LocusZoom web tool. Nominally significant SNPs were investigated for expression quantitative trait loci (eQTLs) using the RegulomeDB database. We employed Bonferroni corrections to account for multiple testing of all SNPs within the breakpoint regions, irrespective of their linkage disequilibrium. The thresholds for statistical significance after Bonferroni correction for the associations between the SNPs within the 17q25.3 breakpoint region and BD, the associations between these SNPs and SZ, and for the gene-wide associations were 7.45E-05, 1.57E-04, and 0.0125, respectively. Gene-wide p-values, based on the fixed-effect Z-scores method, were calculated using the FORGE software, with PGC data and the genotype data from the HapMap II European samples. More information about the FORGE software and the fixed-effect Z score method are available elsewhere.
Result Summary	Four protein-coding genes [coding for (endonuclease V (ENDOV), neuronal pentraxin I (NPTX1), ring finger protein 213 (RNF213), and regulatory-associated protein of mammalian target of rapamycin (mTOR) (RPTOR)] were found to be located within the 17q25.3 breakpoint region. NPTX1 was significantly associated with BD (p=0.004), while ENDOV was significantly associated with SZ (p=0.0075) after Bonferroni correction.