Quantitative multidimensional phenotypes improve genetic analysis of laterality traits

Abstract Handedness is the most commonly investigated lateralised phenotype and is usually measured as a binary left/right category. Its links with psychiatric and neurodevelopmental disorders prompted studies aimed at understanding the underlying genetics, while other measures and side preferences...

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Main Authors: Judith Schmitz, Mo Zheng, Kelvin F. H. Lui, Catherine McBride, Connie S.-H. Ho, Silvia Paracchini
Format: Article
Language:English
Published: Nature Publishing Group 2022-02-01
Series:Translational Psychiatry
Online Access:https://doi.org/10.1038/s41398-022-01834-z
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author Judith Schmitz
Mo Zheng
Kelvin F. H. Lui
Catherine McBride
Connie S.-H. Ho
Silvia Paracchini
author_facet Judith Schmitz
Mo Zheng
Kelvin F. H. Lui
Catherine McBride
Connie S.-H. Ho
Silvia Paracchini
author_sort Judith Schmitz
collection DOAJ
description Abstract Handedness is the most commonly investigated lateralised phenotype and is usually measured as a binary left/right category. Its links with psychiatric and neurodevelopmental disorders prompted studies aimed at understanding the underlying genetics, while other measures and side preferences have been less studied. We investigated the heritability of hand, as well as foot, and eye preference by assessing parental effects (n ≤ 5028 family trios) and SNP-based heritability (SNP-h2, n ≤ 5931 children) in the Avon Longitudinal Study of Parents and Children (ALSPAC). An independent twin cohort from Hong Kong (n = 358) was used to replicate results from structural equation modelling (SEM). Parental left-side preference increased the chance of an individual to be left-sided for the same trait, with stronger maternal than paternal effects for footedness. By regressing out the effects of sex, age, and ancestry, we transformed laterality categories into quantitative measures. The SNP-h2 for quantitative handedness and footedness was 0.21 and 0.23, respectively, which is higher than the SNP-h2 reported in larger genetic studies using binary handedness measures. The heritability of the quantitative measure of handedness increased (0.45) compared to a binary measure for writing hand (0.27) in the Hong Kong twins. Genomic and behavioural SEM identified a shared genetic factor contributing to handedness, footedness, and eyedness, but no independent effects on individual phenotypes. Our analysis demonstrates how quantitative multidimensional laterality phenotypes are better suited to capture the underlying genetics than binary traits.
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spelling doaj.art-66f9df618738468e8a4c63b5f66ac68b2022-12-21T17:24:19ZengNature Publishing GroupTranslational Psychiatry2158-31882022-02-011211810.1038/s41398-022-01834-zQuantitative multidimensional phenotypes improve genetic analysis of laterality traitsJudith Schmitz0Mo Zheng1Kelvin F. H. Lui2Catherine McBride3Connie S.-H. Ho4Silvia Paracchini5School of Medicine, University of St AndrewsDepartment of Psychology, The Chinese University of Hong KongWofoo Joseph Lee Consulting and Counselling Psychology Research Centre, Lingnan UniversityDepartment of Psychology, The Chinese University of Hong KongPsychology Department, The University of Hong KongSchool of Medicine, University of St AndrewsAbstract Handedness is the most commonly investigated lateralised phenotype and is usually measured as a binary left/right category. Its links with psychiatric and neurodevelopmental disorders prompted studies aimed at understanding the underlying genetics, while other measures and side preferences have been less studied. We investigated the heritability of hand, as well as foot, and eye preference by assessing parental effects (n ≤ 5028 family trios) and SNP-based heritability (SNP-h2, n ≤ 5931 children) in the Avon Longitudinal Study of Parents and Children (ALSPAC). An independent twin cohort from Hong Kong (n = 358) was used to replicate results from structural equation modelling (SEM). Parental left-side preference increased the chance of an individual to be left-sided for the same trait, with stronger maternal than paternal effects for footedness. By regressing out the effects of sex, age, and ancestry, we transformed laterality categories into quantitative measures. The SNP-h2 for quantitative handedness and footedness was 0.21 and 0.23, respectively, which is higher than the SNP-h2 reported in larger genetic studies using binary handedness measures. The heritability of the quantitative measure of handedness increased (0.45) compared to a binary measure for writing hand (0.27) in the Hong Kong twins. Genomic and behavioural SEM identified a shared genetic factor contributing to handedness, footedness, and eyedness, but no independent effects on individual phenotypes. Our analysis demonstrates how quantitative multidimensional laterality phenotypes are better suited to capture the underlying genetics than binary traits.https://doi.org/10.1038/s41398-022-01834-z
spellingShingle Judith Schmitz
Mo Zheng
Kelvin F. H. Lui
Catherine McBride
Connie S.-H. Ho
Silvia Paracchini
Quantitative multidimensional phenotypes improve genetic analysis of laterality traits
Translational Psychiatry
title Quantitative multidimensional phenotypes improve genetic analysis of laterality traits
title_full Quantitative multidimensional phenotypes improve genetic analysis of laterality traits
title_fullStr Quantitative multidimensional phenotypes improve genetic analysis of laterality traits
title_full_unstemmed Quantitative multidimensional phenotypes improve genetic analysis of laterality traits
title_short Quantitative multidimensional phenotypes improve genetic analysis of laterality traits
title_sort quantitative multidimensional phenotypes improve genetic analysis of laterality traits
url https://doi.org/10.1038/s41398-022-01834-z
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