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

• Published in: Journal of affective disorders Vol. 145; no. 2; pp. 200 - 207
• Main Authors: Lee, Heon-Jeong, Woo, Hyun Goo, Greenwood, Tiffany A, Kripke, Daniel F, Kelsoe, John R
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 20.02.2013; Elsevier
• Subjects: Adult and adolescent clinical studies; Biological and medical sciences; Bipolar affective disorder; Bipolar disorder; Bipolar Disorder - genetics; Bipolar disorders; Genes; Genetic factors; Genetic Predisposition to Disease; Genome-wide association; Genome-Wide Association Study; Genotype; Haplotypes; Humans; Introns - genetics; Mania; Medical sciences; Mood disorders; NFI Transcription Factors - genetics; Polymorphism, Single Nucleotide; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Seasonal pattern; Seasons; Susceptibility; Variants; Genome-wide association; Bipolar disorder; Seasonal pattern; Mood disorder; Sensitivity; Gene; Seasonal variation; Mania; Genetics; Genetic determinism
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/j.jad.2012.07.032

Abstract 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.