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Genes Contributing to Pain Sensitivity in the Normal Population: An Exome Sequencing Study

Figure 3

The Angiotensin II regulatory network was identified by causal reasoning from 138 genes associated with pain sensitivity.

Causal reasoning uses directed molecular interactions to work upstream from the genes in this study (green) to identify regulators such as angiotensin II (blue) that have a causally correct regulatory role for a significant number of input genes. Correctness is determined by giving each input gene a direction of effect. Here, we presumed a loss of function (e.g. down regulation in activity) to all of our genes. Angiotensin II has direct causal connections to 12 of the genes from our 138, which can be increased to 30 if one intermediary node is allowed in the network (Figure S1). Distribution of novel rare variants identified according to minor allele frequency in a) TUK1 and b) TUK2 datasets.

Figure 3

doi: https://doi.org/10.1371/journal.pgen.1003095.g003