A genome-wide association study of seasonal pattern mania identifies NF1A as a possible susceptibility gene for bipolar disorder

Objective: The use of subphenotypes may be an effective approach for genetic studies of complex diseases. Manic episodes with a seasonal pattern may distinguish phenotypic subgroups of bipolar subjects that may also differ genetically. Method: We have performed a genome-wide association study using GAIN genotype data from the Bipolar Genome Study (BiGS) and bipolar subjects that were categorized as having either seasonal or non-seasonal patterned manic episodes. Results: A bipolar case-only analysis identified three genomic regions that differed between seasonal and non-seasonal patterned manic episodes of bipolar subjects. The most significant association was for rs41350144, which lies within an intron of NF1A gene on 1p31 (P=3.08×10^-7, OR=2.27). Haplotype construction using flanking three SNPs (rs41453448, rs1125777, and rs12568010) spanning 7549 bp showed a more significant association (P=2.12×10^-7, OR=0.4). Conclusions: These data suggest that genetic variants in the NF1A gene region may predispose to seasonal patterned of mania in bipolar disorder.