Regional enrichment analyses on genetic profiles for schizophrenia and bipolar disorder

Schizophr Res. 2018 Feb;192:240-246. doi: 10.1016/j.schres.2017.04.033. Epub 2017 Apr 22.


Both schizophrenia (SZ) and bipolar disorder (BD) are highly heritable psychiatric disorders. The significant genomic risk loci are of great importance but with no guarantee of known functional impact and they cannot totally explain the genetic inheritance. In this study we present regional enrichment analyses across the genome, aiming to strike a balance between individual risk loci and integrated regional effects. Chromosomes were partitioned into 2 million base-pair regions (indicated by an underscore sign in the cytogenetic bands) on which enrichment tests are performed. In the discovery phase, we leverage the Psychiatric Genomics Consortium SZ and BD initial association test results for European Ancestry (EA) population and dbGAP SNP data for African Ancestry (AA) population. 78 and 48 regions show significantly enriched associations with SZ and BD respectively in the EA population, and nine are in common including MHC, 3p21.1, 7p22.3_2, 2q32.3_2, 8q24.3_4, and 19q13.33_1. The most unique SZ associated region is 1p21.3_3, while the most unique BD associated region is 6q25.2_1. For the AA population fewer regions are discovered with only 10% overlapping with that of EA population. A replication test using Wellcome Trust Case Control Consortium data for EA population verified 9% of the SZ enriched regions and 40% of the BD enriched regions. In summary, we showed that regional enrichment analyses produce reliable genetic association profiles using about one tenth of samples compared to single base-pair genome wide association approach. The identified association regions will be useful for further genetic functional studies.

Keywords: African ancestry; Bipolar disorder; European ancestry; Genetic association; Regional enrichment; Schizophrenia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bipolar Disorder / genetics*
  • Blacks / genetics
  • Chromosomes / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Male
  • Polymorphism, Single Nucleotide / genetics*
  • Schizophrenia / genetics*
  • Whites / genetics