RESUMEN
Genetic predisposition of social sensitivity might affect vulnerability to develop psychopathology after early life stress exposure. This study examined whether maternal verbally aggressive behavior in early infancy interacts with oxytocin polymorphisms in developing internalizing symptoms at ages 5-6 and 11-12. In the Amsterdam-Born-Children-and-their-Development (ABCD) study, a large observational, population-based birth cohort, maternal verbally aggressive behavior was assessed in the 13th postnatal week by a self-report questionnaire. Internalizing symptoms at age 5-6 were assessed by maternal report (N = 969) and internalizing symptoms at age 11-12 were assessed by self-report (N = 750). Data on oxytocin receptor polymorphisms rs53576 and rs2268498 and oxytocin polymorphisms rs2740210 and rs4813627 were collected. If the child was carrier of rs2740210 CA/AA polymorphism, exposure to maternal verbally aggressive behavior (10.6%) was positively associated with general anxiety at age 5-6 and emotional symptoms at age 11-12 (p for interaction = 0.011 and p = 0.015, respectively). If the child was carrier of rs4813627 GG (wild type), exposure to maternal verbally aggressive behavior was negatively associated with anxiety sensitivity and emotional symptoms at age 11-12 (p for interaction = 0.011 and p = 0.022, respectively). After exposure to maternal verbally aggressive behavior in early infancy, oxytocin polymorphisms may partly determine a child's vulnerability to internalizing symptoms.
Asunto(s)
Agresión , Síntomas Conductuales/etiología , Síntomas Conductuales/genética , Interacción Gen-Ambiente , Conducta Materna , Oxitocina/genética , Receptores de Oxitocina/genética , Conducta Verbal , Adulto , Síntomas Afectivos/etiología , Síntomas Afectivos/genética , Agresión/fisiología , Ansiedad/etiología , Ansiedad/genética , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Masculino , Conducta Materna/fisiología , Conducta Verbal/fisiologíaRESUMEN
Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.4 × 10(-6)), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 × 10(-8)). Common variants with minor allele frequencies greater than 5% were observed to be associated with height in 37 previously reported loci. In individuals of European ancestry, uncommon SNPs in IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide genotyping arrays, were strongly associated with height (p < 3 × 10(-11)). Conditional analysis within associated regions revealed five additional variants associated with height independent of lead SNPs within the locus, suggesting allelic heterogeneity. Although underpowered to replicate findings from individuals of European ancestry, the direction of effect of associated variants was largely consistent in African American, South Asian, and Hispanic populations. Overall, we show that dense coverage of genes for uncommon SNPs, coupled with large-scale meta-analysis, can successfully identify additional variants associated with a common complex trait.