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FMR1, circadian genes and depression: suggestive associations or false discovery? Cover

FMR1, circadian genes and depression: suggestive associations or false discovery?

Open Access
|Mar 2013

Figures & Tables

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Figure 1

Minor allele frequency versus QIDS score. For the Sleep Clinic sample, the rs25702 minor allele frequency (MAF) with its 95% confidence interval range is plotted versus QIDS score ranges. QIDS scores correspond to the following levels of depression: mild (6–10), moderate (11–15), severe (16–20), and very severe (≥21) depression, where patients with scores <6 are not likely depressed and those >20 would usually not be observed in the clinic because they would need hospitalization. The lower the QIDS and the less depression observed, the more likely a patient was to have a minor allele.

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Figure 2

QIDS scores for 0, 1, or 2 minor alleles. For the Sleep Clinic sample, the QIDS depression score is plotted (with 95% confidence limits) for zero, one, or two minor alleles in rs25702. Since the sample was largely male, there were only 3 females (less than 1%) with two minor alleles in rs28900, rs25714, or rs25702. The small number with two minor alleles accounted for the large confidence limit in QIDS scores for that group. It appeared that women with one or two minor alleles had averaged about the same QIDS score, suggesting a dominant trait associated with lower QIDS score.

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Figure 3

Q-Q plot for Sleep Clinic SNPs. The ranked observed and randomly-expected linear regression probabilities (P values) are plotted for the Sleep Clinic SNPs on a negative log10 scale. Higher values indicate smaller P values with greater significance. The three upper SNPs (from left to right) are FMR1 rs28900, rs25714, and rs25702. The red line indicates the expected trend were there no genomic inflation.

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Figure 4

Stratified Q-Q plot for SNPs Associated with QIDS-SR. For SNP association with QIDS-SR, the ranked observed meta-analysis probabilities (P values) are plotted versus the expected probabilities. The scale is –log10(P), so that points above and to the right represent more significant (i.e. smaller) P values. Unlike Figure 3, only the 614 SNPs are plotted for which meta-analysis P values were available both for the QIDS-SR (Additional file 1, worksheet 1) and for DSPS classification in a dominant logistic genetic model. The P values for QIDS-SR association are stratified by whether the association of that SNP with DSPS was nominally significant (P<0.05). The expectation for 614 SNPs with random association is plotted in the black dashed line. Since the distance of the most deviant p values for PDSPS<0.05 (red line) is approximately 1 log unit from the random expectation (black dotted line) and from the line for PDSPS>0.05 (blue line), one may estimate that the probability of false discovery of pleiotropy for the most significant SNPs was ~0.10. FMR1 SNPs were not included in Figure 4 because the dominant model could not be computed for this part of the X chromosome, but no FMR1 SNP was significantly associated with DSPS in an additive model.

Language: English
Published on: Mar 23, 2013
Published by: Ubiquity Press
In partnership with: Paradigm Publishing Services
Publication frequency: 1 issue per year

© 2013 Daniel F Kripke, Caroline M Nievergelt, Gregory J Tranah, Sarah S Murray, Katharine M Rex, Alexandra P Grizas, Elizabeth K Hahn, Heon-Jeong Lee, John R Kelsoe, Lawrence E Kline, published by Ubiquity Press
This work is licensed under the Creative Commons Attribution 4.0 License.