title: Seasonality shows evidence for polygenic architecture and genetic correlation with schizophrenia and bipolar disorder.
abstract: OBJECTIVE
  To test common genetic variants for association with seasonality (seasonal changes in mood and behavior) and to investigate whether there are shared genetic risk factors between psychiatric disorders and seasonality.
  
  
  METHODS
  Genome-wide association studies (GWASs) were conducted in Australian (between 1988 and 1990 and between 2010 and 2013) and Amish (between May 2010 and December 2011) samples in whom the Seasonal Pattern Assessment Questionnaire (SPAQ) had been administered, and the results were meta-analyzed in a total sample of 4,156 individuals. Genetic risk scores based on results from prior large GWAS studies of bipolar disorder, major depressive disorder (MDD), and schizophrenia were calculated to test for overlap in risk between psychiatric disorders and seasonality.
  
  
  RESULTS
  The most significant association was with rs11825064 (P = 1.7 × 10⁻⁶, β = 0.64, standard error = 0.13), an intergenic single nucleotide polymorphism (SNP) found on chromosome 11. The evidence for overlap in risk factors was strongest for schizophrenia and seasonality, with the schizophrenia genetic profile scores explaining 3% of the variance in log-transformed global seasonality scores. Bipolar disorder genetic profile scores were also associated with seasonality, although at much weaker levels (minimum P value = 3.4 × 10⁻³), and no evidence for overlap in risk was detected between MDD and seasonality.
  
  
  CONCLUSIONS
  Common SNPs of large effect most likely do not exist for seasonality in the populations examined. As expected, there were overlapping genetic risk factors for bipolar disorder (but not MDD) with seasonality. Unexpectedly, the risk for schizophrenia and seasonality had the largest overlap, an unprecedented finding that requires replication in other populations and has potential clinical implications considering overlapping cognitive deficits in seasonal affective disorders and schizophrenia.
authors.affiliation: The University of Queensland, Queensland Brain Institute, Upland Rd, St Lucia, QLD 4072, Brisbane, Australia enda.byrne@uq.edu.au.
authors.forename: Enda M
authors.initials: EM
authors.lastname: Byrne
authors.forename: Uttam K
authors.initials: UK
authors.lastname: Raheja
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Stephens
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Heath
authors.forename: Pamela A F
authors.initials: PA
authors.lastname: Madden
authors.forename: Dipika
authors.initials: D
authors.lastname: Vaswani
authors.forename: Gagan V
authors.initials: GV
authors.lastname: Nijjar
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Ryan
authors.forename: Hassaan
authors.initials: H
authors.lastname: Youssufi
authors.forename: Philip R
authors.initials: PR
authors.lastname: Gehrman
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Naomi R
authors.initials: NR
authors.lastname: Wray
authors.forename: Elliot C
authors.initials: EC
authors.lastname: Nelson
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
authors.forename: Teodor T
authors.initials: TT
authors.lastname: Postolache
mesh_terms: D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000235:genetics / Q000523:psychology; D061365:Amish / Q000235:genetics / Q000523:psychology; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D004200:Diseases in Twins / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D005260:Female; D005838:Genotype; D006801:Humans; D008016:Life Change Events; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D011793:Queensland; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D012565:Schizophrenic Psychology; D014481:United States; D055815:Young Adult