The impact of inherited genetic variation on gene expression in humans is well-established. The majority of known expression quantitative trait loci (eQTLs) impact expression of local genes (
...-eQTLs). More research is needed to identify effects of genetic variation on distant genes (
-eQTLs) and understand their biological mechanisms. One common
-eQTLs mechanism is "mediation" by a local (
) transcript. Thus, mediation analysis can be applied to genome-wide SNP and expression data in order to identify transcripts that are "
-mediators" of
-eQTLs, including those "
-hubs" involved in regulation of many
-genes. Identifying such mediators helps us understand regulatory networks and suggests biological mechanisms underlying
-eQTLs, both of which are relevant for understanding susceptibility to complex diseases. The multitissue expression data from the Genotype-Tissue Expression (GTEx) program provides a unique opportunity to study
-mediation across human tissue types. However, the presence of complex hidden confounding effects in biological systems can make mediation analyses challenging and prone to confounding bias, particularly when conducted among diverse samples. To address this problem, we propose a new method: Genomic Mediation analysis with Adaptive Confounding adjustment (GMAC). It enables the search of a very large pool of variables, and adaptively selects potential confounding variables for each mediation test. Analyses of simulated data and GTEx data demonstrate that the adaptive selection of confounders by GMAC improves the power and precision of mediation analysis. Application of GMAC to GTEx data provides new insights into the observed patterns of
-hubs and
-eQTL regulation across tissue types.
This study reflects on the earliest literary representations in French (approximately 1790-1830) of close relations between black men and white women. Traditionally considered taboo, they are notably ...depicted in two white women writers, Caroline Auguste Fischer, who reinforces racial prejudice, despite an evident fascination with otherness, and Sophie Doin, who reveals a surprising degree of tolerance and elevates the Blanche/Noir couple to totemic status, anticipating Fanon's dream of 'une sainte rencontre' between Blacks and Whites. By freely choosing her black partner the white heroine of Doin's 'Blanche et noir' shows her own and the author's sociopsychological liberation.
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