Handedness and 23 Early Life Characteristics in 37,495 Dutch Twins

Odintsova, Veronika V.; Dongen, Jenny van; Beijsterveldt, Catharina E. M. van; Ligthart, Lannie; Willemsen, Gonneke; Geus, Eco J. C. de; Dolan, Conor V.; Boomsma, Dorret I.

doi:10.1017/thg.2023.23

Cited by 4 publications

(2 citation statements)

References 66 publications

(112 reference statements)

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“…Mixed-handed individuals perform some tasks better with the left hand and some with the right hand, whereas ambidextrous individuals perform a tasks such as writing equally well with both hands, which is rare (3.3%) [5]. The prevalence of non-right-handedness is almost double in twins, with 11.11-16.19% [6,7] compared to 7.23% in singletons [7]. Moreover, an increase in neurodevelopmental delays and higher externalizing problems were reported in mixed-handed twins in a study with over 35.000 Dutch twins [6].…”

Section: Introductionmentioning

confidence: 99%

“…The prevalence of non-right-handedness is almost double in twins, with 11.11-16.19% [6,7] compared to 7.23% in singletons [7]. Moreover, an increase in neurodevelopmental delays and higher externalizing problems were reported in mixed-handed twins in a study with over 35.000 Dutch twins [6]. In clinical samples, metaanalyses revealed significantly increased rates of non-righthandedness for attention deficit hyperactivity disorder [8], autism spectrum disorders [9], posttraumatic stress disorder [10], and schizophrenia [11].…”

Section: Introductionmentioning

confidence: 99%

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Handedness in schizophrenia and affective disorders: a large-scale cross-disorder study

Mundorf,

Lischke,

Peterburs

et al. 2024

Eur Arch Psychiatry Clin Neurosci

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While most people are right-handed, a minority are left-handed or mixed-handed. It has been suggested that mental and developmental disorders are associated with increased prevalence of left-handedness and mixed-handedness. However, substantial heterogeneity exists across disorders, indicating that not all disorders are associated with a considerable shift away from right-handedness. Increased frequencies in left- and mixed-handedness have also been associated with more severe clinical symptoms, indicating that symptom severity rather than diagnosis explains the high prevalence of non-right-handedness in mental disorders. To address this issue, the present study investigated the association between handedness and measures of stress reactivity, depression, mania, anxiety, and positive and negative symptoms in a large sample of 994 healthy controls and 1213 patients with DSM IV affective disorders, schizoaffective disorders, or schizophrenia. A series of complementary analyses revealed lower lateralization and a higher percentage of mixed-handedness in patients with major depression (14.9%) and schizophrenia (24.0%) compared to healthy controls (12%). For patients with schizophrenia, higher symptom severity was associated with an increasing tendency towards left-handedness. No associations were found for patients diagnosed with major depression, bipolar disorder, or schizoaffective disorder. In healthy controls, no association between hand preference and symptoms was evident. Taken together, these findings suggest that both diagnosis and symptom severity are relevant for the shift away from right-handedness in mental disorders like schizophrenia and major depression.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Handedness in schizophrenia and affective disorders: a large-scale cross-disorder study

Mundorf,

Lischke,

Peterburs

et al. 2024

Eur Arch Psychiatry Clin Neurosci

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Exome-wide analysis implicates rare protein-altering variants in human handedness

Schijven,

Soheili-Nezhad,

Fisher

et al. 2024

Nat Commun

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Handedness is a manifestation of brain hemispheric specialization. Left-handedness occurs at increased rates in neurodevelopmental disorders. Genome-wide association studies have identified common genetic effects on handedness or brain asymmetry, which mostly involve variants outside protein-coding regions and may affect gene expression. Implicated genes include several that encode tubulins (microtubule components) or microtubule-associated proteins. Here we examine whether left-handedness is also influenced by rare coding variants (frequencies ≤ 1%), using exome data from 38,043 left-handed and 313,271 right-handed individuals from the UK Biobank. The beta-tubulin gene TUBB4B shows exome-wide significant association, with a rate of rare coding variants 2.7 times higher in left-handers than right-handers. The TUBB4B variants are mostly heterozygous missense changes, but include two frameshifts found only in left-handers. Other TUBB4B variants have been linked to sensorineural and/or ciliopathic disorders, but not the variants found here. Among genes previously implicated in autism or schizophrenia by exome screening, DSCAM and FOXP1 show evidence for rare coding variant association with left-handedness. The exome-wide heritability of left-handedness due to rare coding variants was 0.91%. This study reveals a role for rare, protein-altering variants in left-handedness, providing further evidence for the involvement of microtubules and disorder-relevant genes.

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