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.
Highlights
Handedness is the most obvious manifestation of cerebral lateralization in humans, with more than 90% preferring to use their right hand [1]
To date, only few specific genes have been suggested as candidates influencing handedness: Francks et al (2007) reported evidence for the involvement of the imprinted gene leucine-rich repeat transmembrane neuronal 1 (LRRTM1) on chromosome 2p12 in the development of schizophrenia/schizoaffective disorder and human handedness [12]
We report 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 1113 unrelated healthy Caucasian adults
Summary
Handedness is the most obvious manifestation of cerebral lateralization in humans, with more than 90% preferring to use their right hand [1]. Francks et al (2007) report the association of a three-marker haplotype within an intron of CTNNA2, 137kb upstream of LRRTM1, with schizophrenia when inherited paternally [12]. This haplotype was found to be paternally associated with handedness in a sample of reading-disabled sibships, implying the existence of specific imprinting effects on human brain [12,14,15]. A genome-wide association study for a quantitative measure of relative handskill in individuals with reading disability (RD) revealed association with SNPs in PCSK6 (proprotein convertase subtilisin/kexin type 6, known as PACE4) which is known to have regulatory function during anterior CNS patterning and left-right axis formation [17,18]. The results show a significant association with an intronic 33bp variablenumber tandem repeat (VNTR) polymorphism in PCSK6 (rs10523972) and handedness
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