title: Whole-genome-wide association study in the Bulgarian population reveals HHAT as schizophrenia susceptibility gene.
abstract: OBJECTIVE
  Schizophrenia, the most common major psychiatric disorder (or group of disorders), entails severe decline of higher functions, principally with alterations in cognitive functioning and reality perception. Both genetic and environmental factors are involved in its pathogenesis; however, its genetic background still needs to be clarified. The objective of the study was to reveal genetic markers associated with schizophrenia in the Bulgarian population.
  
  
  METHODS
  We have conducted a genome-wide association study using 554 496 single nucleotide polymorphisms (SNPs) in 188 affected and 376 unaffected Bulgarian individuals. Subsequently, the 100 candidate SNPs that revealed the smallest P-values were further evaluated in an additional set of 99 case and 328 control samples.
  
  
  RESULTS
  We found a significant association between schizophrenia and the intronic SNP rs7527939 in the HHAT gene (P-value of 6.49×10 with an odds ratio of 2.63, 95% confidence interval of 1.89-3.66). We also genotyped additional SNPs within a 58-kb linkage disequilibrium block surrounding the landmark SNP.
  
  
  CONCLUSIONS
  We suggest rs7527939 to be the strongest indicator of susceptibility to schizophrenia in the Bulgarian population within the HHAT locus.
authors.affiliation: Laboratory for International Alliance, RIKEN Center for Genomic Medicine, Yokohama City, Kanagawa, UK.
authors.forename: Elitza T
authors.initials: ET
authors.lastname: Betcheva
authors.forename: Adelina G
authors.initials: AG
authors.lastname: Yosifova
authors.forename: Taisei
authors.initials: T
authors.lastname: Mushiroda
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Sena K
authors.initials: SK
authors.lastname: Karachanak
authors.forename: Irina T
authors.initials: IT
authors.lastname: Zaharieva
authors.forename: Savina P
authors.initials: SP
authors.lastname: Hadjidekova
authors.forename: Ivanka I
authors.initials: II
authors.lastname: Dimova
authors.forename: Radoslava V
authors.initials: RV
authors.lastname: Vazharova
authors.forename: Drozdstoy S
authors.initials: DS
authors.lastname: Stoyanov
authors.forename: Vihra K
authors.initials: VK
authors.lastname: Milanova
authors.forename: Todor
authors.initials: T
authors.lastname: Tolev
authors.forename: George
authors.initials: G
authors.lastname: Kirov
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Draga I
authors.initials: DI
authors.lastname: Toncheva
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D000217:Acyltransferases / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002031:Bulgaria; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D020161:Physical Chromosome Mapping; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results; D012559:Schizophrenia / Q000201:enzymology* / Q000235:genetics*; D055815:Young Adult
chemical_list: D000217:Acyltransferases; C105599:HHAT protein, human