PCSK6 VNTR Polymorphism Is Associated with Degree of Handedness but Not Direction of Handedness

Abstract

Although the left and right human cerebral hemispheres differ both functionally and anatomically, the mechanisms that underlie the establishment of these hemispheric specializations, as well as their physiological and behavioral implications, remain largely unknown. Since cerebral asymmetry is strongly correlated with handedness, and handedness is assumed to be influenced by a number of genetic and environmental factors, we performed an association study of LRRTM1 rs6733871 and a number of polymorphisms in PCSK6 and different aspects of handedness assessed with the Edinburgh handedness inventory in a sample of unrelated healthy adults (n = 1113). An intronic 33bp variable-number tandem repeat (VNTR) polymorphism in PCSK6 (rs10523972) shows a significant association (significance threshold: p<0.0025, adjusted for multiple comparisons) with a handedness category comparison (P = 0.0005) and degree of handedness (P = 0.001). These results provide further evidence for the role of PCSK6 as candidate for involvement in the biological mechanisms that underlie the establishment of normal brain lateralization and thus handedness and support the assumption that the degree of handedness, instead the direction, may be the more appropriate indicator of cerebral organization.

On the other hand: including left-handers in cognitive neuroscience and neurogenetics

“…Statistically significant differences between activity in the left versus right hemisphere are indicated by an asterisk. seem to be subject to imprinting and may be linked to the degree rather than direction of handedness 128 . PCSK6 encodes a protease enzyme that cleaves Nodal, a protein that has a role in the regulation of the left-right visceral axis (of the heart, lungs, and so on) in early embryogenesis 127 .…”

Stability of right visual field advantage in an international lateralized lexical decision task irrespective of participants’ sex, handedness or bilingualism

“…We calculated the following laterality index: ((sum of right hand crosses -sum of left hand crosses) / sum of all crosses) *100. Thus, scores ranged from -100 to 100 with negative values indicating a left hand preference and positive values a right hand preference (including zero) (Arning et al, 2013;Nicholls, Thomas, Loetscher, & Grimshaw, 2013). Based on the laterality index, participants were allocated to one of the following groups: left-handers (LI's between -100 and -50), mixed-handers (LI's between -50 to 50), and right-handers (LI's between 50 to 100).…”

The Genetics of Asymmetry: Whole Exome Sequencing in a Consanguineous Turkish Family with an Overrepresentation of Left-Handedness

“…Thus, most authors today agree that handedness is likely to be a multifactorial trait that is determined by several different genetic and non-genetic factors (e.g., [5][6][7][8]). A number of contributing loci have been identified by GWAS and candidate gene studies using handedness questionnaires or hand skill tests like the pegboard test as phenotypes, e.g., LRRTM1, PCSK6 and AR [9][10][11][12][13][14][15]. However, the general understanding is that there is likely a large number of yet unidentified genetic contributions to handedness [5].…”

“…However, it is commonly measured as a continuous variable using a lateralization quotient (LQ) [18], ranging from −100 (consistent left-handedness) to +100 (consistent right-handedness). Interestingly, findings from a recent PCSK6 candidate gene study on handedness showed that the direction and degree of handedness might underlie differential genetic influences [9]. Thus, using the LQ as a phenotype instead of differentiating between left-and right-handers could potentially yield interesting insights into the genetics of handedness.…”