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Comment
. 2023 Dec 21;6(1):1295.
doi: 10.1038/s42003-023-05658-5.

Genetic differentiation at probe SNPs leads to spurious results in meQTL discovery

Gillian L Meeks  1 , Brenna M Henn  2   3 , Shyamalika Gopalan  4
Affiliations
Comment

Genetic differentiation at probe SNPs leads to spurious results in meQTL discovery

Gillian L Meeks et al. Commun Biol. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. SNPs in Li et al.’s meQTL CpG probes are more differentiated than SNPs in non-meQTL CpG probes between 1000 Genomes EUR and AFR super-populations.
a Fst distributions between meQTL (red) and non-meQTL (gray) probe SNPs are significantly different (two-tailed t-test p-value = 2.2e−16, 95% confidence interval for the difference in mean Fst [0.20–0.23]). The boxplots show the median (horizontal line), interquartile range (box), and 1.5x interquartile range (whiskers). b Probe SNP frequencies in AFR vs. EUR of the same probe SNPs (red points, Li et al.’s meQTL; gray points, non-meQTL) further highlight that they tend to be significantly differentiated, i.e., they tend to deviate from the dashed black line that indicates identical EUR and AFR allele frequencies.
Fig. 2
Fig. 2. Probe SNPs bias effect size estimates.
a MeQTL involving CpGs with probe SNPs (blue) have larger effect sizes than those without (yellow) (95% confidence interval for difference in mean effect size [0.28, 0.45], two-tailed t-test p-value = 1.44e−15). b A cubic regression of the distance between the probe SNP and target CpG explains 42% of the variation in meQTL effect size for the 351 CpG probes with SNPs (F-test p-value over a quadratic model = 0.0006). c LA-specific meQTL involving CpGs with probe SNPs (blue) have larger differences in effect sizes (Δ) between European and African local ancestry than those without (yellow) (95% confidence interval for difference in mean Δ effect size [0.24, 0.70], two-tailed t-test p-value = 0.0002). d A quadratic regression of the distance between the probe SNP and target CpG explains 25% of the variation in Δ effect sizes for the 58 CpG probes with SNPs (F-test p-value over a linear model = 0.014). The boxplots in a and c show the median (horizontal line), interquartile range (box), and 1.5× interquartile range (whiskers). The ribbons in b and d show 2 standard errors above and below the model predictions.
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