Evidence for plasticity genotypes in a gene-gene-environment interaction: the TRAILS study.
The purpose was to study how functional polymorphisms in the brain derived neurotrophic factor gene (BDNF val66met) and the serotonin transporter gene linked promotor region (5-HTTLPR) interact with childhood adversities in predicting Effortful Control. Effortful Control refers to the ability to regulate behavior in a goal-directed manner and is an interesting endophenotype for psychopathology because of its heritability and the association of low Effortful Control with both internalizing and externalizing problems. In a longitudinal population-based study Effortful Control was assessed with the parent version of the Early Adolescent Temperament Questionnaire at age 11. Pregnancy and delivery adversities and childhood events were assessed in a parent interview at age 11. Long-term difficulties until age 11 were assessed with a parent questionnaire at age 13.5. Blood or buccal cells were collected at age 16 for genotyping the rs6265 and rs25531 SNPs and the 5-HTTLPR length polymorphism. The study included 1032 complete data sets. Effortful Control was significantly predicted by the interaction between BDNF val66met, 5-HTTLPR and childhood events. The BDNF val66met val/val-5-HTTLPR l'/l' genotype was unaffected by childhood events, while having either at least one BDNF val66met met or 5-HTTLPR s' allele (l'/l'-met-carrier; l'/s'-val/val; s'/s'-val/val) made children sensitive to childhood events. Predictions of Effortful Control by pregnancy and delivery adversities and long-term difficulties were largely independent of genotype. We concluded that the l'/l'-met-carrier, l'/s'-val/val and the s'/s'-val/val genotypes showed greatest plasticity while the l'/l'-val/val genotype was unaffected by childhood events.
Nederhof
E
E
Interdisciplinary Center for Psychiatric Epidemiology, Department of Psychiatry and Unit of Genetic Epidemiology & Bioinformatics, Department of Epidemiology (HR), University Medical Center Groningen, University of Groningen, The Netherlands. e.nederhof@med.umcg.nl
Bouma
E M C
EM
Riese
H
H
Laceulle
O M
OM
Ormel
J
J
Oldehinkel
A J
AJ
D000223:Adaptation, Psychological; D000293:Adolescent; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002648:Child; D002657:Child Development / Q000502:physiology; D002675:Child, Preschool; D015331:Cohort Studies; D056344:Executive Function / Q000502:physiology*; D005838:Genotype; D006040:Goals; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007389:Internal-External Control; D008016:Life Change Events; D008137:Longitudinal Studies; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D000297:Psychology, Adolescent; D055500:Resilience, Psychological; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012927:Social Control, Informal; D013315:Stress, Psychological / Q000150:complications* / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins