Literature DB >> 30424865

Polygenic Risk Scores Derived From a Tourette Syndrome Genome-wide Association Study Predict Presence of Tics in the Avon Longitudinal Study of Parents and Children Cohort.

Mohamed Abdulkadir1, Carol A Mathews2, Jeremiah M Scharf3, Dongmei Yu3, Jay A Tischfield4, Gary A Heiman4, Pieter J Hoekstra5, Andrea Dietrich5.   

Abstract

BACKGROUND: Tourette syndrome (TS) has a well-established genetic background, but its genetic architecture remains largely unknown. The authors investigated the role of polygenic risk scores (PRSs) derived from a TS genome-wide association study in relation to the occurrence of tics and associated traits in a general population cohort.
METHODS: Using the most recent TS genome-wide association study (n = 4819 cases; n = 9488 controls) as the discovery sample, PRSs were calculated in Avon Longitudinal Study of Parents and Children participants (n = 8941). Regression analyses were used to assess whether PRS predicted the presence and chronicity of tics, and symptom severity of obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, and autism spectrum disorder in Avon Longitudinal Study of Parents and Children participants.
RESULTS: Following correction for multiple testing, the PRS significantly predicted the presence (R2 = .48%, p empirical = .01, Q = .04) but not the chronicity (R2 = .16%, p empirical = .07, Q = .14) of tics in the Avon Longitudinal Study of Parents and Children cohort; it did not predict the severity of obsessive-compulsive disorder (R2 = .11%, p empirical = .11, Q = .15), attention-deficit/hyperactivity disorder (R2 = .09%, p empirical = .19, Q = .21), or autism spectrum disorder (R2 = .12%, p empirical = .09, Q = .14).
CONCLUSIONS: The authors found a significant polygenic component of tics occurring in a general population cohort based on PRS derived from a genome-wide association study of individuals with a TS diagnosis. This finding supports the notion that tics along a spectrum from nonclinical to clinical symptom levels share a similar genetic background.
Copyright © 2018 Society of Biological Psychiatry. All rights reserved.

Entities:  

Keywords:  Attention-deficit/hyperactivity disorder; Autism spectrum disorder; Avon Longitudinal Study of Parents and Children (ALSPAC); Obsessive-compulsive disorder; Polygenic risk score; Tourette syndrome

Mesh:

Year:  2018        PMID: 30424865      PMCID: PMC6342633          DOI: 10.1016/j.biopsych.2018.09.011

Source DB:  PubMed          Journal:  Biol Psychiatry        ISSN: 0006-3223            Impact factor:   13.382


  32 in total

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Authors:  Shaun Purcell; Benjamin Neale; Kathe Todd-Brown; Lori Thomas; Manuel A R Ferreira; David Bender; Julian Maller; Pamela Sklar; Paul I W de Bakker; Mark J Daly; Pak C Sham
Journal:  Am J Hum Genet       Date:  2007-07-25       Impact factor: 11.025

2.  De Novo Coding Variants Are Strongly Associated with Tourette Disorder.

Authors:  A Jeremy Willsey; Thomas V Fernandez; Dongmei Yu; Robert A King; Andrea Dietrich; Jinchuan Xing; Stephan J Sanders; Jeffrey D Mandell; Alden Y Huang; Petra Richer; Louw Smith; Shan Dong; Kaitlin E Samocha; Benjamin M Neale; Giovanni Coppola; Carol A Mathews; Jay A Tischfield; Jeremiah M Scharf; Matthew W State; Gary A Heiman
Journal:  Neuron       Date:  2017-05-03       Impact factor: 17.173

3.  ALSPAC--the Avon Longitudinal Study of Parents and Children. I. Study methodology.

Authors:  J Golding; M Pembrey; R Jones
Journal:  Paediatr Perinat Epidemiol       Date:  2001-01       Impact factor: 3.980

4.  Heritability of tic disorders: a twin-family study.

Authors:  N R Zilhão; M C Olthof; D J A Smit; D C Cath; L Ligthart; C A Mathews; K Delucchi; D I Boomsma; C V Dolan
Journal:  Psychol Med       Date:  2016-12-15       Impact factor: 7.723

5.  Prevalence of Tourette syndrome and chronic tics in the population-based Avon longitudinal study of parents and children cohort.

Authors:  Jeremiah M Scharf; Laura L Miller; Carol A Mathews; Yoav Ben-Shlomo
Journal:  J Am Acad Child Adolesc Psychiatry       Date:  2011-12-23       Impact factor: 8.829

6.  Cohort Profile: the Avon Longitudinal Study of Parents and Children: ALSPAC mothers cohort.

Authors:  Abigail Fraser; Corrie Macdonald-Wallis; Kate Tilling; Andy Boyd; Jean Golding; George Davey Smith; John Henderson; John Macleod; Lynn Molloy; Andy Ness; Susan Ring; Scott M Nelson; Debbie A Lawlor
Journal:  Int J Epidemiol       Date:  2012-04-16       Impact factor: 7.196

7.  Genetic risk for attention-deficit/hyperactivity disorder contributes to neurodevelopmental traits in the general population.

Authors:  Joanna Martin; Marian L Hamshere; Evangelia Stergiakouli; Michael C O'Donovan; Anita Thapar
Journal:  Biol Psychiatry       Date:  2014-02-25       Impact factor: 13.382

8.  Meta-Analysis of Tourette Syndrome and Attention Deficit Hyperactivity Disorder Provides Support for a Shared Genetic Basis.

Authors:  Fotis Tsetsos; Shanmukha S Padmanabhuni; John Alexander; Iordanis Karagiannidis; Margaritis Tsifintaris; Apostolia Topaloudi; Dimitrios Mantzaris; Marianthi Georgitsi; Petros Drineas; Peristera Paschou
Journal:  Front Neurosci       Date:  2016-07-22       Impact factor: 4.677

Review 9.  Pathogenetic model for Tourette syndrome delineates overlap with related neurodevelopmental disorders including Autism.

Authors:  R A Clarke; S Lee; V Eapen
Journal:  Transl Psychiatry       Date:  2012-09-04       Impact factor: 6.222

10.  Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population.

Authors:  Elise B Robinson; Beate St Pourcain; Verneri Anttila; Jack A Kosmicki; Brendan Bulik-Sullivan; Jakob Grove; Julian Maller; Kaitlin E Samocha; Stephan J Sanders; Stephan Ripke; Joanna Martin; Mads V Hollegaard; Thomas Werge; David M Hougaard; Benjamin M Neale; David M Evans; David Skuse; Preben Bo Mortensen; Anders D Børglum; Angelica Ronald; George Davey Smith; Mark J Daly
Journal:  Nat Genet       Date:  2016-03-21       Impact factor: 38.330

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6.  Enhancing neuroimaging genetics through meta-analysis for Tourette syndrome (ENIGMA-TS): A worldwide platform for collaboration.

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