DNA methylation in peripheral tissues and left-handedness

Abstract

Handedness has low heritability and epigenetic mechanisms have been proposed as an etiological mechanism. To examine this hypothesis, we performed an epigenome-wide association study of left-handedness. In a meta-analysis of 3914 adults of whole-blood DNA methylation, we observed that CpG sites located in proximity of handedness-associated genetic variants were more strongly associated with left-handedness than other CpG sites (P = 0.04), but did not identify any differentially methylated positions. In longitudinal analyses of DNA methylation in peripheral blood and buccal cells from children (N = 1737), we observed moderately stable associations across age (correlation range [0.355–0.578]), but inconsistent across tissues (correlation range [− 0.384 to 0.318]). We conclude that DNA methylation in peripheral tissues captures little of the variance in handedness. Future investigations should consider other more targeted sources of tissue, such as the brain.

Handedness in post-traumatic stress disorder: A meta-analysis

“…The reasons why many, but not all, neurodevelopmental and psychiatric disorders are associated with a higher frequency of non-right-handedness, while none is related to a higher frequency of right-handedness are not well understood . In general, it has been suggested that both genetic and non-genetic factors relevant for handedness may to some extent overlap with those involved in the pathogenesis of neurodevelopmental and psychiatric disorders (Cuellar-Partida et al, 2021;Odintsova et al, 2022;Schmitz et al, 2017). Regarding non-genetic factors, stress is of particular importance, as it has been linked to both the pathogenesis of almost all neurodevelopmental and psychiatric disorders and the ontogenesis of handedness and other forms of hemispheric asymmetries (Berretz et al, 2020b).…”

Broadening the scope: Increasing phenotype diversity in laterality research

“…This is often the case for e.g., handedness, which is one of the most prominent lateralized phenotypes in humans, with 89.4% of the population being right-handers (Papadatou-Pastou et al, 2020 ). Handedness is a complex trait emerging from multiple genetic, epigenetic, environmental, and interacting effects (Güntürkün and Ocklenburg, 2017 ; Ocklenburg et al, 2017 ; Kovel and Francks, 2019 ; Cuellar-Partida et al, 2021 ; Odintsova et al, 2022 ). About 25% of variance in human handedness has a genetic origin (Medland et al, 2006 ).…”

“…Since a large part of the variance in handedness cannot be explained by genetic variation, epigenetic factors likely come into play (Schmitz et al, 2017 ). A recent epigenome-wide association study (EWAS) investigated the association between handedness and several hundred thousand cytosine-phosphate-guanine nucleotide base pairings (CpGs) from whole-blood samples (Odintsova et al, 2022 ). Methylations of two regions were significantly associated with left-handedness: BLCAP and IAH1.…”

Cognitive and Neurophysiological Models of Brain Asymmetry

“…Over the last decade, tremendous progress has been made in research on brain asymmetries, due to large-scale consortium or databank studies [5]. For example, largescale databank studies have investigated the genetics of structural brain asymmetries [6] and handedness [7][8][9][10], as well as the influence of early life factors on handedness [11], and the role of epigenetic processes in handedness ontogenesis [12]. Unfortunately, despite the vast number of data-driven studies on brain asymmetries, more recent publications featuring theoretical models that aim to provide mechanistic explanations of hemispheric asymmetries are sparse in the field.…”