Peer Review Report For: Negligible heritability of language laterality assessed by functional transcranial Doppler ultrasound: a twin study [version 1; peer review: 1 approved with reservations]. Wellcome Open Research 2019, 4:161

Abstract

Background: Prior studies have estimated heritability of around 0.25 for the trait of handedness, with studies of structural brain asymmetry giving estimates in a similar or lower range. Little is known about heritability of functional language lateralization. This report describes heritability estimates using functional language laterality and handedness phenotypes in a twin sample previously reported by Wilson and Bishop (2018). Methods: The total sample consisted of 194 twin pairs (49% monozygotic) aged from 6 to 11 years. A language laterality index was obtained for 141 twin pairs, who completed a protocol where relative blood flow through left and right middle cerebral arteries was measured using functional transcranial Doppler ultrasound (fTCD) while the child described animation sequences. Handedness data was available from the Edinburgh Handedness Inventory (EHI) and Quantification of Hand Preference (QHP) for all 194 pairs. Heritability was assessed using conventional structural equation modeling, assuming no effect of shared environment (AE model). Results: For the two handedness measures, heritability estimates (95% CI) were consistent with prior research: .25 (.03 - .34) and .18 (0 – .31) respectively for the EHI and QHP. For the language laterality index, however, the twin-cotwin correlations were close to zero for both MZ and DZ twins, and the heritability estimate was zero (0 - .15). Conclusions: A single study cannot rule out a genetic effect on language lateralisation. It is possible that the low twin-cotwin correlations were affected by noisy data: although the split-half reliability of the fTCD-based laterality index was high (0.85), we did not have information on test-retest reliability in children, which is likely to be lower. We cannot reject the hypothesis that there is low but nonzero heritability for this trait, but our data suggest that individual variation in language lateralisation is predominantly due to stochastic variation in neurodevelopment.