Further evidence for a parent-of-origin effect at the NOP9 locus on language-related phenotypes

Background - Specific language impairment (SLI) is a common neurodevelopmental disorder, observed in 5–10 % of children. Family and twin studies suggest a strong genetic component, but relatively few candidate genes have been reported to date. A recent genome-wide association study (GWAS) described the first statistically significant association specifically for a SLI cohort between a missense variant (rs4280164) in the NOP9 gene and language-related phenotypes under a parent-of-origin model. Replications of these findings are particularly challenging because the availability of parental DNA is required. Methods - We used two independent family-based cohorts characterised with reading- and language-related traits: a longitudinal cohort (n = 106 informative families) including children with language and reading difficulties and a nuclear family cohort (n = 264 families) selected for dyslexia. Results - We observed association with language-related measures when modelling for parent-of-origin effects at the NOP9 locus in both cohorts: minimum P = 0.001 for phonological awareness with a paternal effect in the first cohort and minimum P = 0.0004 for irregular word reading with a maternal effect in the second cohort. Allelic and parental trends were not consistent when compared to the original study. Conclusions - A parent-of-origin effect at this locus was detected in both cohorts, albeit with different trends. These findings contribute in interpreting the original GWAS report and support further investigations of the NOP9 locus and its role in language-related traits. A systematic evaluation of parent-of-origin effects in genetic association studies has the potential to reveal novel mechanisms underlying complex traits

Further evidence for a parent-of-origin effect at the NOP9 locus on language-related phenotypes

Background: Specific Language Impairment (SLI) is a common neurodevelopmental disorder, observed in 5-10% of children. Family and twin studies suggest a strong genetic component, but relatively few candidate genes have been reported to date. A recent genome-wide association study (GWAS) described the first statistically significant association specifically for a SLI cohort between a missense variant (rs4280164) in the NOP9 gene and language-related phenotypes under a parent-of-origin model. Replications of these findings are particularly challenging because the availability of parental DNA is required. Methods: We used two independent family-based cohorts characterised with reading- and language-related traits: a longitudinal cohort (n = 106 informative families) including children with language and reading difficulties and a nuclear family cohort (n = 264 families) selected for dyslexia. Results: We observed association with languagerelated measures when modelling for parent-of-origin effects at the NOP9 locus in both cohorts: minimum P = 0.001 for phonological awareness with a paternal effect in the first cohort and minimum P = 0.0004 for irregular word reading with a maternal effect in the second cohort. Allelic and parental trends were not consistent when compared to the original study. Conclusions: A parent-of-origin effect at this locus was detected in both cohorts, albeit with different trends. These findings contribute in interpreting the original GWAS report and support further investigations of the NOP9 locus and its role in language-related traits. A systematic evaluation of parent-of-origin effects in genetic association studies has the potential to reveal novel mechanisms underlying complex traits

ManyDogs 1: A multi-lab replication study of dogs' pointing comprehension

To promote collaboration across canine science, address replicability issues, and advance open science practices within animal cognition, we have launched the ManyDogs consortium, modeled on similar ManyX projects in other fields. We aimed to create a collaborative network that (a) uses large, diverse samples to investigate and replicate findings, (b) promotes open science practices of pre-registering hypotheses, methods, and analysis plans, (c) investigates the influence of differences across populations and breeds, and (d) examines how different research methods and testing environments influence the robustness of results. Our first study combines a phenomenon that appears to be highly reliable—dogs’ ability to follow human pointing—with a question that remains controversial: do dogs interpret pointing as a social communicative gesture or as a simple associative cue? We collected data (N = 455) from 20 research sites on two conditions of a 2-alternative object choice task: (1) Ostensive (pointing to a baited cup after making eye-contact and saying the dog’s name); (2) Non-ostensive (pointing without eye-contact, after a throat-clearing auditory control cue). Comparing performance between conditions, while both were significantly above chance, there was no significant difference in dogs’ responses. This result was consistent across sites. Further, we found that dogs followed contralateral, momentary pointing at lower rates than has been reported in prior research, suggesting that there are limits to the robustness of point-following behavior: not all pointing styles are equally likely to elicit a response. Together, these findings underscore the important role of procedural details in study design and the broader need for replication studies in canine science