Chunk #15 — Three examples of misspecified models in the G×E literature — Cicchetti et al., 2007: A gene-by-environment or a gender-by-environment interaction?
Using a mixed-gender (54% male) sample of 267 individuals, Cicchetti et al. (24) found that a repeat polymorphism in the X-linked monoamine oxidase A (MAOA) gene interacted with childhood maltreatment to predict depression. The investigators coded “high activity” of the gene as having more than 3.5 repeats (63% allele frequency) and “low activity” as fewer than 3.5 repeats. Because males have only one copy of the gene, coding the genetic variable for males was straight-forward, but it was unclear how to code heterozygous (high/low) females, who were therefore excluded. However, this coding strategy probably induced a relationship between MAOA activity and gender. The proportion of males was ~.63 for the high activity allele and ~.37 for the low activity allele. However, for females these proportions were ~.632=.40 for the high activity and ~.372=.14 for the low activity alleles (assuming Hardy-Weinberg equilibrium). Thus, females were probably over-represented in the high activity group: there were ~1.7 times more males in the high vs. low activity groups but ~2.9 times more females in the high vs. low activity groups. Investigators controlled for the
