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Williams Syndrome neuroanatomical score associates with GTF2IRD1 in large-scale magnetic resonance imaging cohorts: a proof of concept for multivariate endophenotypes.

ABSTRACT: Despite great interest in using magnetic resonance imaging (MRI) for studying the effects of genes on brain structure in humans, current approaches have focused almost entirely on predefined regions of interest and had limited success. Here, we used multivariate methods to define a single neuroanatomical score of how William's Syndrome (WS) brains deviate structurally from controls. The score is trained and validated on measures of T1 structural brain imaging in two WS cohorts (training, n?=?38; validating, n?=?60). We then associated this score with single nucleotide polymorphisms (SNPs) in the WS hemi-deleted region in five cohorts of neurologically and psychiatrically typical individuals (healthy European descendants, n?=?1863). Among 110 SNPs within the 7q11.23 WS chromosomal region, we found one associated locus (p?=?5e-5) located at GTF2IRD1, which has been implicated in animal models of WS. Furthermore, the genetic signals of neuroanatomical scores are highly enriched locally in the 7q11.23 compared with summary statistics based on regions of interest, such as hippocampal volumes (n?=?12,596), and also globally (SNP-heritability?=?0.82, se?=?0.25, p?=?5e-4). The role of genetic variability in GTF2IRD1 during neurodevelopment extends to healthy subjects. Our approach of learning MRI-derived phenotypes from clinical populations with well-established brain abnormalities characterized by known genetic lesions may be a powerful alternative to traditional region of interest-based studies for identifying genetic variants regulating typical brain development.

SUBMITTER: Fan CC

PROVIDER: S-EPMC5993783 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Williams Syndrome neuroanatomical score associates with GTF2IRD1 in large-scale magnetic resonance imaging cohorts: a proof of concept for multivariate endophenotypes.

Fan Chun Chieh CC Schork Andrew J AJ Brown Timothy T TT Spencer Barbara E BE Akshoomoff Natacha N Chen Chi-Hua CH Kuperman Joshua M JM Hagler Donald J DJ Steen Vidar M VM Le Hellard Stephanie S Håberg Asta Kristine AK Espeseth Thomas T Andreassen Ole A OA Dale Anders M AM Jernigan Terry L TL Halgren Eric E

Translational psychiatry 20180608 1

Despite great interest in using magnetic resonance imaging (MRI) for studying the effects of genes on brain structure in humans, current approaches have focused almost entirely on predefined regions of interest and had limited success. Here, we used multivariate methods to define a single neuroanatomical score of how William's Syndrome (WS) brains deviate structurally from controls. The score is trained and validated on measures of T1 structural brain imaging in two WS cohorts (training, n = 38; ...[more]

PMID: 29884845

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Project description:Infant sociability is generally conceived in terms of dyadic capacities and behaviors. Recently, quantitative evidence has been published to support arguments that infants achieve a criterion for groupness: the capacity to interact simultaneously with two others. Such studies equate this capacity with alternating dyadic acts to the two other members of an interacting trio. Here we propose a stricter threefold criterion for infant groupness, of which the crux is whether the social behavior of an infant at time B is shown to be influenced by what two or more group-members were previously doing at time A. We test the viability of this conceptualization: (a) through its justification of the novel laboratory procedure of studying infant sociability in infant-peer quartets (rather than trios); and, (b) in an analysis of a pilot study of gaze-behavior recorded in 5-min interactions among two quartets of infants aged 6-9 months. We call this a 'proof of concept' because our aim is to show that infants are capable of groupness, when groupness is conceptualized in a supra-dyadic way-not that all infants will manifest it, nor that all conditions will produce it, nor that it is commonplace in infants' everyday lives. We found that both quartets did achieve the minimum criterion of groupness that we propose: mutual gaze predicting coordinated gaze (where two babies, A and B, are looking at each other, and B is then looked at by C, and sometimes D) more strongly than the reverse. There was a significant absence of 'parallel mutual gaze,' where the four babies pair off. We conclude that, under specific conditions, preverbal infants can manifest supra-dyadic groupness. Infants' capacities to exhibit groupness by 9 months of age, and the paucity of parallel mutual gaze in our data, run counter to the assumption that infant sociability, when in groups, is always generated by a dyadic program. Our conceptualization and demonstration of groupness in 8-month-olds thus opens a host of empirical, theoretical, and practical questions about the sociability and care of young babies.

Dataset Information

Williams Syndrome neuroanatomical score associates with GTF2IRD1 in large-scale magnetic resonance imaging cohorts: a proof of concept for multivariate endophenotypes.

Publications

Williams Syndrome neuroanatomical score associates with GTF2IRD1 in large-scale magnetic resonance imaging cohorts: a proof of concept for multivariate endophenotypes.

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