Fig 1.
ESR1 gene structure, mRNA isoforms and variants (A), and allelic mRNA ratios in Stanley PFC brain samples(B). A) Estrogen receptor α gene map showing exon structure, location of genotyped SNPs, and the mRNA isoforms ESR1-203 and ESR1-008. The 150 kb upstream region contains multiple alternative promoters and first exons. With deep sequencing, additional exons have been added to the ESR1 locus, in particular within the 150 kb 5’ region; numbering of the exons here reflects historical usage. B) Absolute allelic ratios measured in 70 Stanley PFC samples using 2 marker SNPs, sorted by disease status. *subjects heterozygous for rs2144025. Dashed lines: cut off 2.0 for high AEI ratios and 1.4 for moderate AEI. +2 samples with discrepant allelic ratios from the two marker SNPs were counted as moderate AEI. None of the subjects with moderate and high AEI were in the control group.rs2144025is in low LD with the two marker SNPs rs3798577 (R2 = 0.003) and rs1801132 (R2 = 0.044) in the CEU(1000 genomes) cohort; therefore, only absolute AEI ratios are shown.
Table 1.
Association of ESR1 variants with large allelic expression imbalance (ratios >2) in the Stanley prefrontal cortex brain samples.
Table 2.
Distribution of AEI ratio category versus diagnosis.
Fig 2.
Minor allele frequency (MAF) of rs2144025 and age of onset in 211 females (A) and 197 males (B) with bipolar disorder in GAIN (dotted lines: MAF in GAIN controls; f = 12.8%; males = 15.6%). Age of BD onset was nominally associated with rs2144025 in females (additive model p = 0.04), but did not reach significance in males (p = 0.29).
Table 3.
Associations of rs2144025C>T with bipolar bisorder in the GAIN Bipolar Disorder study.
Table 4.
Associations of rs2144025C>T with bipolar episode subtype in the GAIN Bipolar Disorder study.
Table 5.
Association of rs2144025 with grandiose delusions in both male and female Caucasian schizophrenia patients from the GAIN Schizophrenia GWAS.
Table 6.
Subject count and allele frequency information for the grandiose delusions diagnosis in Caucasian schizophrenia patients from the GAIN Schizophrenia GWAS.
Table 7.
Associations of rs2144025 with comorbid psychiatric diagnoses in the GAIN Attention Deficit Hyperactivity Disorder study.
Table 8.
Associations of rs2144025 in eMERGE GWAS with psychological disorders of Caucasian children (eMERGE Boston Children’s Hospital).