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      Using Polygenic Profiles to Predict Variation in Language and Psychosocial Outcomes in Early and Middle Childhood

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          Abstract

          Purpose

          Children with poor language tend to have worse psychosocial outcomes compared to their typically developing peers. The most common explanations for such adversities focus on developmental psychological processes whereby poor language triggers psychosocial difficulties. Here, we investigate the possibility of shared biological effects by considering whether the same genetic variants, which are thought to influence language development, are also predictors of elevated psychosocial difficulties during childhood.

          Method

          Using data from the U.K.-based Avon Longitudinal Study of Parents and Children, we created a number of multi–single-nucleotide polymorphism polygenic profile scores, based on language and reading candidate genes ( ATP2C2, CMIP, CNTNAP2, DCDC2, FOXP2, and KIAA0319, 1,229 single-nucleotide polymorphisms) in a sample of 5,435 children.

          Results

          A polygenic profile score for expressive language (8 years) that was created in a discovery sample ( n = 2,718) predicted not only expressive language (8 years) but also peer problems (11 years) in a replication sample ( n = 2,717).

          Conclusions

          These findings provide a proof of concept for the use of such a polygenic approach in child language research when larger data sets become available. Our indicative findings suggest consideration should be given to concurrent intervention targeting both linguistic and psychosocial development as early language interventions may not stave off later psychosocial difficulties in children.

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          Most cited references41

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          Phase 2 of CATALISE: a multinational and multidisciplinary Delphi consensus study of problems with language development: Terminology

          Background Lack of agreement about criteria and terminology for children's language problems affects access to services as well as hindering research and practice. We report the second phase of a study using an online Delphi method to address these issues. In the first phase, we focused on criteria for language disorder. Here we consider terminology. Methods The Delphi method is an iterative process in which an initial set of statements is rated by a panel of experts, who then have the opportunity to view anonymised ratings from other panel members. On this basis they can either revise their views or make a case for their position. The statements are then revised based on panel feedback, and again rated by and commented on by the panel. In this study, feedback from a second round was used to prepare a final set of statements in narrative form. The panel included 57 individuals representing a range of professions and nationalities. Results We achieved at least 78% agreement for 19 of 21 statements within two rounds of ratings. These were collapsed into 12 statements for the final consensus reported here. The term ‘Language Disorder’ is recommended to refer to a profile of difficulties that causes functional impairment in everyday life and is associated with poor prognosis. The term, ‘Developmental Language Disorder’ (DLD) was endorsed for use when the language disorder was not associated with a known biomedical aetiology. It was also agreed that (a) presence of risk factors (neurobiological or environmental) does not preclude a diagnosis of DLD, (b) DLD can co‐occur with other neurodevelopmental disorders (e.g. ADHD) and (c) DLD does not require a mismatch between verbal and nonverbal ability. Conclusions This Delphi exercise highlights reasons for disagreements about terminology for language disorders and proposes standard definitions and nomenclature.
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            GWAS of 126,559 individuals identifies genetic variants associated with educational attainment.

            A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (coefficient of determination R(2) ≈ 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for ≈2% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics.
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              No Support for Historical Candidate Gene or Candidate Gene-by-Interaction Hypotheses for Major Depression Across Multiple Large Samples

              Interest in candidate gene and candidate gene-by-environment interaction hypotheses regarding major depressive disorder remains strong despite controversy surrounding the validity of previous findings. In response to this controversy, the present investigation empirically identified eighteen candidate genes for depression studied ten or more times and examined evidence for their relevance to depression phenotypes. Utilizing data from large population-based and case-control samples ( n ranging from 62,138 to 443,264 across subsamples), we conducted a series of preregistered analyses examining polymorphism main effects, polymorphism × environmental moderator interactions, and gene-level effects across a number of operational definitions of depression (e.g., lifetime diagnosis, current severity, episode recurrence) and environmental moderators (e.g., sexual or physical abuse during childhood, socioeconomic adversity). There was no clear evidence for any candidate gene polymorphism associations with depression phenotypes or any polymorphism × environmental moderator effects. As a set, depression candidate genes were no more associated with depression phenotypes than noncandidate genes. We demonstrate that phenotypic measurement error is unlikely to account for these null findings. Our results do not support previous depression candidate gene findings, wherein large genetic effects are frequently reported in samples orders of magnitude smaller than those examined here. Instead, our results suggest that early hypotheses about depression candidate genes were incorrect and that the large number of associations reported in the depression candidate gene literature are likely to be false positives.
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                Author and article information

                Journal
                J Speech Lang Hear Res
                J. Speech Lang. Hear. Res
                JSLHR
                Journal of Speech, Language, and Hearing Research : JSLHR
                American Speech-Language-Hearing Association
                1092-4388
                1558-9102
                19 August 2019
                September 2019
                19 August 2019
                : 62
                : 9
                : 3381-3396
                Affiliations
                [a ]Department of Biological and Medical Sciences, Headington Campus, Oxford Brookes University, United Kingdom
                [b ]Faculty of Education, University of Cambridge, United Kingdom
                [c ]School of Health Sciences, The University of Manchester, United Kingdom
                [d ]Department of Biostatistics, Institute of Psychiatry, King's College London, United Kingdom
                [e ]School of Psychological Sciences, University of Strathclyde, United Kingdom
                [f ]Department of Education, Derwent College, University of York, United Kingdom
                Author notes

                Disclosure: The authors have declared that no competing interests existed at the time of publication.

                Correspondence to Umar Toseeb: umar.toseeb@ 123456york.ac.uk

                Editor-in-Chief: Sean Redmond

                Editor: Stephen Camarata

                Article
                23814764000300140072
                10.1044/2019_JSLHR-L-19-0001
                6808346
                31425657
                b31e3b8a-ff8d-48bb-8d9c-7ae26401a621
                Copyright © 2019 The Authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 02 January 2019
                : 07 March 2019
                : 29 April 2019
                Page count
                Pages: 16
                Funding
                The U.K. Medical Research Council and Wellcome (Grant 102215/2/13/2) and the University of Bristol provide core support for the Avon Longitudinal Study of Parents and Children (ALSPAC). This publication is the work of the authors, and Newbury, Gibson, Conti-Ramsden, Pickles, Durkin, and Toseeb will serve as guarantors for the contents of this article. A comprehensive list of grant funding is available on the ALSPAC website ( http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). The analysis undertaken in this article was specifically funded by the Economic and Social Research Council (Grants ES/P001955/1 and ES/P001955/2). G. C.-R. is supported by the National Institute for Health Research (NIHR) Manchester. A. P. is partially supported by NIHR NF-SI-0617-10120 and the Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, or the Department of Health and Social Care. J. G. is partially supported by the LEGO Foundation and by the Arts and Humanities Research Council (Grant AH/N004671/1).
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