CHRM2, parental monitoring, and adolescent externalizing behavior: evidence for gene-environment interaction.
- Authors
- Dick, Danielle M; Meyers, Jacquelyn L; Latendresse, Shawn J; Creemers, Hanneke E; Lansford, Jennifer E; Pettit, Gregory S; Bates, John E; Dodge, Kenneth A; Budde, John; Goate, Alison; Buitelaar, Jan K; Ormel, Johannes; Verhulst, Frank C; Huizink, Anja C
- Year
- 2011
- Journal
- Psychological science
- PMID
- 21441226
- DOI
- 10.1177/0956797611403318
- PMCID
- PMC3391964
Psychologists, with their long-standing tradition of studying mechanistic processes, can make important contributions to further characterizing the risk associated with genes identified as influencing risk for psychiatric disorders. We report one such effort with respect to CHRM2, which codes for the cholinergic muscarinic 2 receptor and was of interest originally for its association with alcohol dependence. We tested for association between CHRM2 and prospectively measured externalizing behavior in a longitudinal, community-based sample of adolescents, as well as for moderation of this association by parental monitoring. We found evidence for an interaction in which the association between the genotype and externalizing behavior was stronger in environments with lower parental monitoring. There was also suggestion of a crossover effect, in which the genotype associated with the highest levels of externalizing behavior under low parental monitoring had the lowest levels of externalizing behavior at the extreme high end of parental monitoring. The difficulties involved in distinguishing mechanisms of gene-environment interaction are discussed.
Location of (top), and correlations between (bottom), the single-nucleotide polymorphisms (SNPs) genotyped in the CHRM2 gene in the Child Development Project (CDP) sample. The output was obtained from Haploview (Barrett, Fry, Maller, & Daly, 2005) using the CEPH (Centre d’Etude du Polymorphisme Humain) data from the HapMap database (The International HapMap Consortium, 2003). Shading indicates the degree of correlation as measured by D′ (Hedrick & Kumar, 2001); darker red shading indicates higher correlations, and white shading indicates that markers are unlinked or uncorrelated. The numbers inside the diamonds are R2 values, another measure of correlation between SNPs. R2 is more sensitive to allele frequencies than D′ is and ranges from 0 to 1.0 (as a standard correlation does). The black triangle grouping a subset of SNPs on the figure indicates a block (33 kilobases, or kb) of SNPs that are highly correlated (as defined by criteria detailed in Gabriel et al., 2002). Not all SNPs genotyped in the CDP sample were in the HapMap database; in these cases, proxy SNPs that were the SNPs most highly correlated with the genotyped SNPs are listed: rs1364409 represents rs36210735 (r2 = .7), and rs1364407 represents rs978437 (r2 = .9). The dagger and asterisks indicate SNPs that showed a significant or marginally significant interaction with parental monitoring (†p < .10; *p < .05). In addition to the nine SNPs genotyped in the CDP sample, the figure shows the location of a SNP that showed a significant interaction with parental monitoring in the TRacking Adolescents’ Individual Lives Survey (TRAILS; marked €).
Regression lines showing externalizing behavior as a function of parental monitoring and genotype for each of the three CHRM2 single-nucleotide polymorphisms (SNPs) showing a significant gene-environment interaction in the Child Development Project sample. A median split on parental monitoring was used to graph the data to illustrate the shape of the interaction; however, a continuous measure of parental monitoring was used in the statistical analyses reported in the text.
Regression lines showing externalizing behavior as a function of parental monitoring and genotype for the single-nucleotide polymorphism (SNP) showing a significant gene-environment interaction in the TRacking Adolescents’ Individual Lives Survey (TRAILS). A median split on parental monitoring was used to graph the data to illustrate the shape of the interaction; however, a continuous measure of parental monitoring was used in the statistical analyses reported in the text.
Different models of gene-environment interactions. The diathesis-stress framework (a) predicts that there is a stronger association between genotype and outcome under adverse environmental conditions than under benign environmental conditions (a fan-shaped interaction). In contrast, the differential-susceptibility hypothesis (b) predicts that the individuals at highest risk under adverse environmental conditions are at lowest risk under positive environmental conditions (a crossover interaction).
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| Gene-environment interaction in psychological traits and disorders. | Dick DM | — | 2011 | → |