title: Linkage analysis in a Dutch population isolate shows no major gene for left-handedness or atypical language lateralization.
abstract: Cerebral dominance of language function and hand preference are suggested to be heritable traits with possible shared genetic background. However, joined genetic studies of these traits have never been conducted. We performed a genetic linkage study in 37 multigenerational human pedigrees of both sexes (consisting of 355 subjects) enriched with left-handedness in which we also measured language lateralization. Hand preference was measured with the Edinburgh Handedness Inventory, and language lateralization was measured with functional transcranial Doppler during language production. The estimated heritability of left-handedness and language lateralization in these pedigrees is 0.24 and 0.31, respectively. A parametric major gene model was tested for left-handedness. Nonparametric analyses were performed for left-handedness, atypical lateralization, and degree of language lateralization. We did not observe genome-wide evidence for linkage in the parametric or nonparametric analyses for any of the phenotypes tested. However, multiple regions showed suggestive evidence of linkage. The parametric model showed suggestive linkage for left-handedness in the 22q13 region [heterogeneity logarithm of odds (HLOD) = 2.18]. Nonparametric multipoint analysis of left-handedness showed suggestive linkage in the same region [logarithm of odds (LOD) = 2.80]. Atypical language lateralization showed suggestive linkage in the 7q34 region (LODMax = 2.35). For strength of language lateralization, we observed suggestive linkage in the 6p22 (LODMax = 2.54), 7q32 (LODMax = 1.93), and 9q33 (LODMax = 2.10) regions. We did not observe any overlap of suggestive genetic signal between handedness and the extent of language lateralization. The absence of significant linkage argues against the presence of a major gene coding for both traits; rather, our results are suggestive of these traits being two independent polygenic complex traits.
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands, M.Somers@umcutrecht.nl.
authors.forename: Metten
authors.identifier: http://orcid.org/0000-0002-9381-5596
authors.initials: M
authors.lastname: Somers
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands, Department of Human Genetics David Geffen School of Medicine at University of California, Los Angeles, Gonda (Goldschmied) Neuroscience and Genetics Research Center, Los Angeles, California 90095-7088, Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, Los Angeles, California 90095-1761, and.
authors.forename: Roel A
authors.initials: RA
authors.lastname: Ophoff
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
authors.forename: Maartje F
authors.initials: MF
authors.lastname: Aukes
authors.affiliation: Department of Human Genetics David Geffen School of Medicine at University of California, Los Angeles, Gonda (Goldschmied) Neuroscience and Genetics Research Center, Los Angeles, California 90095-7088.
authors.forename: Rita M
authors.initials: RM
authors.lastname: Cantor
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
authors.forename: Marco P
authors.initials: MP
authors.lastname: Boks
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Dauwan
authors.affiliation: Department of General Practice, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, The Netherlands.
authors.forename: Kees L
authors.initials: KL
authors.lastname: de Visser
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
authors.forename: René S
authors.initials: RS
authors.lastname: Kahn
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
authors.forename: Iris E
authors.initials: IE
authors.lastname: Sommer
mesh_terms: D000328:Adult; D001921:Brain / Q000033:anatomy & histology* / Q000502:physiology; D005260:Female; D007839:Functional Laterality / Q000235:genetics*; D008040:Genetic Linkage; D006801:Humans; D007802:Language; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D017585:Ultrasonography, Doppler, Transcranial; D055815:Young Adult
keywords: asymmetry; genetics; hand-preference; language lateralization; left-handedness; linkage analysis