Transmission disequilibrium tests confirm the link between DRD4 gene polymorphism and infant attachment

Abstract

Following up the results of a previous population association study (Lakatos et al. [2000: Mol Psychiatry 5:633-637; Lakatos et al. [2002: Mol Psychiatry 7:27-31]) by analyses based on parental genetic data confirmed the link between infant attachment and the dopamine D4 receptor (DRD4) gene. Extended transmission disequilibrium tests (ETDT) were performed to determine whether biased transmission of exon III 48 basepair repeat alleles occurred to infants displaying disorganized and secure attachment behavior with their mothers. The overall allele-wise TDTs were significant for both groups (P = 0.038 and 0.020, respectively): a trend for preferential transmission of the seven-repeat allele to disorganized infants was observed (TDT(chi)(2) = 3.27, df = 1, P = 0.071), and there was a significant non-transmission of the same allele to securely attached infants (TDT(chi)(2) = 6.00, df = 1, P = 0.014). Analysis of haplotypes of the exon III repeat and the -521 C/T promoter polymorphisms in family trios showed that the transmission bias in the larger secure group was due to the low-rate transmission of the T.7 haplotype containing both the seven-repeat and the -521 T alleles (TDT(chi)(2) = 4.46, df = 1, P = 0.035). This suggests that not carrying the T.7 haplotype of the DRD4 gene may act as a resilience factor in the optimal development of early attachment.

Infant genotype may moderate sensitivity to maternal affective communications: Attachment disorganization, quality of care, and the DRD4 polymorphism

“…Analysis of the -521 C/T regulatory (promoter) polymorphism of the same gene revealed that the association of the 7-repeat allele and disorganized attachment was observed only in the presence of the -521T allele (Lakatos et al, 2002). While a Dutch study failed to replicate this result in a small twin sample (Bakermans-Kranenburg & van IJzendoorn, 2004), further family-based transmission disequilibrium tests (TDT) in the Hungarian sample have found a highly significant non-transmission of the 7-repeat allele to securely attached infants, as well as a trend for preferential transmission to disorganized infants (Gervai et al, 2005). …”

“…Control for genetic stratification-In the ethnically homogeneous Hungarian sample, DRD4 genotypes in both the infant and the parental groups were in Hardy-Weinberg equilibrium, reflecting a random combination and stable frequencies of the DRD4 repeat alleles in this population (Gervai et al, 2005;Lakatos et al, 2000). For the ethnically heterogeneous US sample, 40 random marker polymorphisms distributed evenly along the human genome (1-3 markers per chromosome) were analyzed.…”

“…Lyons-Ruth et al (1999) developed the AMBIANCE coding scheme to assess disrupted communication between mother and infant, and reported the link between maternal behavior and disorganized attachment. The Hungarian group found an association between a polymorphism of the DRD4 gene and disorganized attachment (Lakatos et al, 2000;Gervai et al, 2005). The present collaborative work investigated the interplay between genetic and caregiving contributions to disorganized attachment.…”

The molecular genetic architecture of human personality: beyond self-report questionnaires

“…117,[160][161][162][163][164][165] As we first noted, 164,165 the study of temperament traits in children offers the opportunity to study gene effects at a time in development when environmental effects are conjectured to be minimal and genetic associations might be more robustly demonstrated.…”

2.47 the Dopamine D4 Receptor Gene, Birth Weight, Early Maternal Care, Maternal Depression Over the Postnatal Time Period, and the Prediction of Disorganized Attachment at 36-Months of Age: A Prospective Gene X Environment Analysis

“…Gervai et al (2005) Bakermans-Kranenburg & van Ijzendoorn, 2004;Gervai et al, 2007;Lee Raby et al, 2013;Luijk et al, 2011;Spangler et al, 2009; Strangely, Luijk et al (2011) actually found opposite trends in each cohort. In the American cohort, infants without the 7R allele developed higher levels of security if their mother was more sensitive but in the Dutch cohort, the trend was in the opposite direction.…”