Figure 2.

The Interaction between rs1783165 and rs1673426 Associated with the Expression of PKHD1L1 May Be a Ceiling Effect

The ceiling effect, caused by limitations in the detectable range of gene expression, has a hallmark pattern—both variants have main effects with concordant direction of effect, and the interaction term has a discordant direction.

(A and B) The minor allele of rs1673426 (A) increases the expression of PKHD1L1. The minor allele of rs1783165 (B) also increases the expression of PKHD1L1, meaning both variants have a concordant direction of effect.

(C) The interaction plot depicts the mean gene expression for all individuals with the specified genotype combination, with each line representing the number of minor alleles at rs1673426. When there is only one minor allele at rs1673426, the mean gene expression increases for each minor allele at rs1783165; however, when there are two minor alleles at rs1673426, the increase in gene expression due to minor alleles at rs1783165 reaches a “maximum” at one minor allele. There is no additional increase in expression for having two minor alleles at rs1783165. This is denoted by the flat line connecting the two genotype combinations. Given that each minor allele at rs1783165 increases gene expression on the background of one minor allele at rs1673426, and that the maximum reached on the background of two minor alleles at rs1673426 is very close to the maximum gene expression levels possible to observe, we consider this an example of the ceiling effect.