Biology subjects

de Kovel, C. G. F.

Publications and source records attributed to de Kovel, C. G. F..

3 recordsLinked to original sources

bioRxiv2018

The molecular genetics of hand preference revisited

Hand preference is a prominent behavioural trait linked to human brain asymmetry. A handful of genetic variants have been reported to associate with hand preference or quantitative measures related to it. Most of these reports were on the basis of limited sample sizes, by current standards for genetic analysis of complex traits. Here we performed a genome-wide association analysis of hand preference in the large, population-based UK Biobank cohort (N=331,037). We used gene-set enrichment analysis to investigate whether genes involved in visceral asymmetry are particularly relevant to hand preference, following one previous report. We found no evidence implicating any specific candidate variants previously reported. We also found no evidence that genes involved in visceral laterality play a role in hand preference. It remains possible that some of the previously reported genes or pathways are relevant to hand preference as assessed in other ways, or else are relevant within specific disorder populations. However, some or all of the earlier findings are likely to be false positives, and none of them appear relevant to hand preference as defined categorically in the general population. Within the UK Biobank itself, a significant association implicates the gene MAP2 in handedness.

genetics↗

bioRxiv2018

Early life factors influencing hand preference in the UK biobank cohort

Hand preference is a conspicuous variation in human behaviour, with a worldwide proportion of around 90% of people preferring to use the right hand for many tasks, and 10% the left hand. We used the large, general population cohort of the UK biobank (~500,000 participants) to study possible relations between early life factors and adult hand preference. The probability of being left-handed was affected by the year and location of birth, likely due to cultural effects. In addition, handedness was affected by birthweight, being part of a multiple birth, season of birth, breastfeeding, and sex, with each effect remaining significant after accounting for all others. Maternal smoking showed no association with handedness. Analysis of genome-wide genotype data showed that left-handedness was very weakly heritable, but shared no genetic basis with birthweight. Although on average left-handers and right-handers differed for a number of early life factors, all together these factors had only a minimal predictive value for individual hand preference. Therefore other, unknown effects must be involved, including possible environmental factors, and/or random developmental variation with respect to the left-right formation of the embryonic brain.\n\nSignificance statementLeft-right laterality is an important aspect of human brain organization which is set up early in development. Left-handedness is an overt and relatively prevalent form of atypical brain laterality. Various, often related, early life factors have been previously studied in relation to handedness, but often in small samples, or samples with biased selection schemes. Here we have performed the largest ever study of left-handedness in relation to early life factors. Left-handedness was very weakly heritable and there were significant effects of various factors such as birthweight, which remained significant after controlling for all others. However, considered all together, early life factors still had poor predictive power for the handedness of any given individual. Very early developmental perturbations, caused by environmental or chance effects in embryonic development, are therefore likely to cause left-handedness.

developmental biology↗

bioRxiv2018

Subtle left-right asymmetry of gene expression profiles in embryonic and foetal human brains

Left-right laterality is an important aspect of human brain organization for which the genetic basis is poorly understood. Using RNA sequencing data we contrasted gene expression in left- and right-sided samples from several structures of the anterior central nervous systems of post mortem human embryos and fetuses. While few individual genes stood out as significantly lateralized, most structures showed evidence of laterality of their overall transcriptomic profiles. These left-right differences showed overlap with age-dependent changes in expression, indicating lateralized maturation rates, but not consistently in left-right orientation over all structures. Brain asymmetry may therefore originate in multiple locations, or if there is a single origin, it is earlier than 5 weeks post conception, with structure-specific lateralized processes already underway by this age. This pattern is broadly consistent with the weak correlations reported between various aspects of adult brain laterality, such as language dominance and handedness.

genomics↗