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Sebastian Ocklenburg - One of the best experts on this subject based on the ideXlab platform.
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the functional genetics of Handedness and language lateralization insights from gene ontology pathway and disease association analyses
Frontiers in Psychology, 2017Co-Authors: Judith Schmitz, Onur Gunturkun, Stephanie Lor, Rena Klose, Sebastian OcklenburgAbstract:Handedness and language lateralization are partially determined by genetic influences. It has been estimated that at least 40 (and potentially more) possibly interacting genes may influence the ontogenesis of hemispheric asymmetries. Recently, it has been suggested that analyzing the genetics of hemispheric asymmetries on the level of gene ontology sets, rather than at the level of individual genes, might be more informative for understanding the underlying functional cascades. Here, we performed gene ontology, pathway and disease association analyses on genes that have previously been associated with Handedness and language lateralization. Significant gene ontology sets for Handedness were anatomical structure development, pattern specification (especially asymmetry formation) and biological regulation. Pathway analysis highlighted the importance of the TGF-beta signaling pathway for Handedness ontogenesis. Significant gene ontology sets for language lateralization were responses to different stimuli, nervous system development, transport, signaling, and biological regulation. Despite the fact that some authors assume that Handedness and language lateralization share a common ontogenetic basis, gene ontology sets barely overlap between phenotypes. Compared to genes involved in Handedness, which mostly contribute to structural development, genes involved in language lateralization rather contribute to activity-dependent cognitive processes. Disease association analysis revealed associations of genes involved in Handedness with diseases affecting the whole body, while genes involved in language lateralization were specifically engaged in mental and neurological diseases. These findings further support the idea that Handedness and language lateralization are ontogenetically independent, complex phenotypes.
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left right axis differentiation and functional lateralization a haplotype in the methyltransferase encoding gene setdb2 might mediate Handedness in healthy adults
Molecular Neurobiology, 2016Co-Authors: Sebastian Ocklenburg, Wanda M Gerding, Larissa Arning, Joerg T Epplen, Onur Gunturkun, Jan G Hengstler, Denis A AkkadAbstract:Handedness is a multifactorial trait, and genes contributing to the differentiation of the left-right axis during embryogenesis have been identified as a major gene group associated with this trait. The methyltransferase SETDB2 (SET domain, bifurcated 2) has been shown to regulate structural left-right asymmetry in the vertebrate central nervous system by suppressing fgf8 expression. Here, we investigated the relation of genetic variation in SETDB2—and its paralogue SETDB1—with different Handedness phenotypes in 950 healthy adult participants. We identified a haplotype on SETDB2 for which homozygous individuals showed a significantly lower lateralization quotient for Handedness than the rest of the cohort after correction for multiple comparisons. Moreover, direction of Handedness was significantly associated with genetic variation in this haplotype. This effect was mainly, but not exclusively, driven by the sequence variation rs4942830, as individuals homozygous for the A allele of this single nucleotide polymorphism had a significantly lower lateralization quotient than individuals with at least one T allele. These findings further confirm a role of genetic pathways relevant for structural left-right axis differentiation for functional lateralization. Moreover, as the protein encoded by SETDB2 regulates gene expression epigenetically by histone H3 methylation, our findings highlight the importance of investigating the role of epigenetic modulations of gene expression in relation to Handedness.
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left right axis differentiation and functional lateralization a haplotype in the methyltransferase encoding gene setdb2 might mediate Handedness in healthy adults
Molecular Neurobiology, 2016Co-Authors: Sebastian Ocklenburg, Wanda M Gerding, Larissa Arning, Joerg T Epplen, Onur Gunturkun, Jan G Hengstler, Christian Beste, Denis A AkkadAbstract:Handedness is a multifactorial trait, and genes contributing to the differentiation of the left-right axis during embryogenesis have been identified as a major gene group associated with this trait. The methyltransferase SETDB2 (SET domain, bifurcated 2) has been shown to regulate structural left-right asymmetry in the vertebrate central nervous system by suppressing fgf8 expression. Here, we investigated the relation of genetic variation in SETDB2—and its paralogue SETDB1—with different Handedness phenotypes in 950 healthy adult participants. We identified a haplotype on SETDB2 for which homozygous individuals showed a significantly lower lateralization quotient for Handedness than the rest of the cohort after correction for multiple comparisons. Moreover, direction of Handedness was significantly associated with genetic variation in this haplotype. This effect was mainly, but not exclusively, driven by the sequence variation rs4942830, as individuals homozygous for the A allele of this single nucleotide polymorphism had a significantly lower lateralization quotient than individuals with at least one T allele. These findings further confirm a role of genetic pathways relevant for structural left-right axis differentiation for functional lateralization. Moreover, as the protein encoded by SETDB2 regulates gene expression epigenetically by histone H3 methylation, our findings highlight the importance of investigating the role of epigenetic modulations of gene expression in relation to Handedness.
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Handedness and the x chromosome the role of androgen receptor cag repeat length
Scientific Reports, 2015Co-Authors: Larissa Arning, Wanda M Gerding, Sebastian Ocklenburg, Joerg T Epplen, Onur Gunturkun, Jan G Hengstler, Stefanie Schulz, Vanessa Ness, Michael Falkenstein, Christian BesteAbstract:Prenatal androgen exposure has been suggested to be one of the factors influencing Handedness, making the androgen receptor gene (AR) a likely candidate gene for individual differences in Handedness. Here, we examined the relationship between the length of the CAG-repeat in AR and different Handedness phenotypes in a sample of healthy adults of both sexes (n = 1057). Since AR is located on the X chromosome, statistical analyses in women heterozygous for CAG-repeat lengths are complicated by X chromosome inactivation. We thus analyzed a sample of women that were homozygous for the CAG-repeat length (n = 77). Mixed-Handedness in men was significantly associated with longer CAG-repeat blocks and women homozygous for longer CAG-repeats showed a tendency for stronger left-Handedness. These results suggest that Handedness in both sexes is associated with the AR CAG-repeat length, with longer repeats being related to a higher incidence of non-right-Handedness. Since longer CAG-repeat blocks have been linked to less efficient AR function, these results implicate that differences in AR signaling in the developing brain might be one of the factors that determine individual differences in brain lateralization.
Ketil Joachim Oedegaard - One of the best experts on this subject based on the ideXlab platform.
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non right Handedness is associated with migraine and soft bipolarity in patients with mood disorders
Journal of Affective Disorders, 2008Co-Authors: Ole Bernt Fasmer, Ketil Joachim Oedegaard, Kenneth HugdahlAbstract:Abstract Background There is a substantial body of data showing differences in the functioning of the two hemispheres in unipolar depressive and bipolar disorders. Migraine is a frequent co-morbid disorder in these patients, and it has been proposed that migraine may be associated with left-Handedness. It would therefore be interesting to study migraine and Handedness in a population of patients with mood disorders. Methods A total of 201 patients with an index episode of either major depression or mania were interviewed with a semi-structured interview based partly on DSM-IV criteria and partly on TEMPS-I for affective temperaments. The criteria of the Headache Classification Committee of the International Headache Society were used to establish the diagnosis of migraine. Hand preference was assessed using the Edinburgh inventory, and the patients were classified as having right-, left-, or mixed-Handedness. Results In the whole group 117 patients had migraine (58%) and 59 (29%) were classified as having non-right hand preference. There was a significant increased prevalence of non-right-Handedness in the migraine group (37% vs. 19%, p = 0.021, Chi-square test; OR 2.5; 95% CI 1.3 –4.8, p = 0.007). In patients with cyclothymic, hyperthymic or irritable temperaments the prevalence of non-right-Handedness (42%) was significantly higher ( p = 0.013, Chi-square test; OR 2.2, 95% CI 1.2–4.3) compared to patients with a depressive or no affective temperament (24%). The prevalence of non-right-Handedness was also significantly higher both in patients with co-morbid eating disorders (48% vs. 26%, p = 0.008 Chi-square test; OR 2.7, 95% CI 1.3–5.9, p = 0.01) and asthma (45% vs. 26%, p = 0.026 Chi-square test; OR 2.3, 95% CI 1.1–5.1, p = 0.029). Limitations Non-blind evaluation of affective diagnosis, migraine and Handedness. Conclusions Our main finding supports the hypothesis that non-right-Handedness is associated with migraine and bipolar affective temperaments (“soft bipolarity”) in a sample of patients with major affective disorders.
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research report non right Handedness is associated with migraine and soft bipolarity in patients with mood disorders
2008Co-Authors: Ole Bernt Fasmer, Kenneth Hugdahl, Ketil Joachim OedegaardAbstract:Background: There is a substantial body of data showing differences in the functioning of the two hemispheres in unipolar depressive and bipolar disorders. Migraine is a frequent co-morbid disorder in these patients, and it has been proposed that migraine may be associated with left-Handedness. It would therefore be interesting to study migraine and Handedness in a population of patients with mood disorders. Methods: A total of 201 patients with an index episode of either major depression or mania were interviewed with a semi-structured interview based partly on DSM-IV criteria and partly on TEMPS-I for affective temperaments. The criteria of the Headache Classification Committee of the International Headache Society were used to establish the diagnosis of migraine. Hand preference was assessed using the Edinburgh inventory, and the patients were classified as having right-, left-, or mixed-Handedness. Results: In the whole group 117 patients had migraine (58%) and 59 (29%) were classified as having non-right hand preference. There was a significant increased prevalence of non-right-Handedness in the migraine group (37% vs. 19%, p=0.021, Chi-square test; OR 2.5; 95% CI 1.3 –4.8, p=0.007). In patients with cyclothymic, hyperthymic or irritable temperaments the prevalence of non-right-Handedness (42%) was significantly higher (p=0.013, Chi-square test; OR 2.2, 95% CI 1.2–4.3) compared to patients with a depressive or no affective temperament (24%). The prevalence of non-right-Handedness was also significantly higher both in patients with co-morbid eating disorders (48% vs. 26%, p=0.008 Chi-square test; OR 2.7, 95% CI 1.3–5.9, p=0.01) and asthma (45% vs. 26%, p=0.026 Chi-square test; OR 2.3, 95% CI 1.1–5.1, p=0.029). Limitations: Non-blind evaluation of affective diagnosis, migraine and Handedness. Conclusions: Our main finding supports the hypothesis that non-right-Handedness is associated with migraine and bipolar affective temperaments (“soft bipolarity”) in a sample of patients with major affective disorders. © 2007 Elsevier B.V. All rights reserved.
Denis A Akkad - One of the best experts on this subject based on the ideXlab platform.
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left right axis differentiation and functional lateralization a haplotype in the methyltransferase encoding gene setdb2 might mediate Handedness in healthy adults
Molecular Neurobiology, 2016Co-Authors: Sebastian Ocklenburg, Wanda M Gerding, Larissa Arning, Joerg T Epplen, Onur Gunturkun, Jan G Hengstler, Denis A AkkadAbstract:Handedness is a multifactorial trait, and genes contributing to the differentiation of the left-right axis during embryogenesis have been identified as a major gene group associated with this trait. The methyltransferase SETDB2 (SET domain, bifurcated 2) has been shown to regulate structural left-right asymmetry in the vertebrate central nervous system by suppressing fgf8 expression. Here, we investigated the relation of genetic variation in SETDB2—and its paralogue SETDB1—with different Handedness phenotypes in 950 healthy adult participants. We identified a haplotype on SETDB2 for which homozygous individuals showed a significantly lower lateralization quotient for Handedness than the rest of the cohort after correction for multiple comparisons. Moreover, direction of Handedness was significantly associated with genetic variation in this haplotype. This effect was mainly, but not exclusively, driven by the sequence variation rs4942830, as individuals homozygous for the A allele of this single nucleotide polymorphism had a significantly lower lateralization quotient than individuals with at least one T allele. These findings further confirm a role of genetic pathways relevant for structural left-right axis differentiation for functional lateralization. Moreover, as the protein encoded by SETDB2 regulates gene expression epigenetically by histone H3 methylation, our findings highlight the importance of investigating the role of epigenetic modulations of gene expression in relation to Handedness.
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left right axis differentiation and functional lateralization a haplotype in the methyltransferase encoding gene setdb2 might mediate Handedness in healthy adults
Molecular Neurobiology, 2016Co-Authors: Sebastian Ocklenburg, Wanda M Gerding, Larissa Arning, Joerg T Epplen, Onur Gunturkun, Jan G Hengstler, Christian Beste, Denis A AkkadAbstract:Handedness is a multifactorial trait, and genes contributing to the differentiation of the left-right axis during embryogenesis have been identified as a major gene group associated with this trait. The methyltransferase SETDB2 (SET domain, bifurcated 2) has been shown to regulate structural left-right asymmetry in the vertebrate central nervous system by suppressing fgf8 expression. Here, we investigated the relation of genetic variation in SETDB2—and its paralogue SETDB1—with different Handedness phenotypes in 950 healthy adult participants. We identified a haplotype on SETDB2 for which homozygous individuals showed a significantly lower lateralization quotient for Handedness than the rest of the cohort after correction for multiple comparisons. Moreover, direction of Handedness was significantly associated with genetic variation in this haplotype. This effect was mainly, but not exclusively, driven by the sequence variation rs4942830, as individuals homozygous for the A allele of this single nucleotide polymorphism had a significantly lower lateralization quotient than individuals with at least one T allele. These findings further confirm a role of genetic pathways relevant for structural left-right axis differentiation for functional lateralization. Moreover, as the protein encoded by SETDB2 regulates gene expression epigenetically by histone H3 methylation, our findings highlight the importance of investigating the role of epigenetic modulations of gene expression in relation to Handedness.
Onur Gunturkun - One of the best experts on this subject based on the ideXlab platform.
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the functional genetics of Handedness and language lateralization insights from gene ontology pathway and disease association analyses
Frontiers in Psychology, 2017Co-Authors: Judith Schmitz, Onur Gunturkun, Stephanie Lor, Rena Klose, Sebastian OcklenburgAbstract:Handedness and language lateralization are partially determined by genetic influences. It has been estimated that at least 40 (and potentially more) possibly interacting genes may influence the ontogenesis of hemispheric asymmetries. Recently, it has been suggested that analyzing the genetics of hemispheric asymmetries on the level of gene ontology sets, rather than at the level of individual genes, might be more informative for understanding the underlying functional cascades. Here, we performed gene ontology, pathway and disease association analyses on genes that have previously been associated with Handedness and language lateralization. Significant gene ontology sets for Handedness were anatomical structure development, pattern specification (especially asymmetry formation) and biological regulation. Pathway analysis highlighted the importance of the TGF-beta signaling pathway for Handedness ontogenesis. Significant gene ontology sets for language lateralization were responses to different stimuli, nervous system development, transport, signaling, and biological regulation. Despite the fact that some authors assume that Handedness and language lateralization share a common ontogenetic basis, gene ontology sets barely overlap between phenotypes. Compared to genes involved in Handedness, which mostly contribute to structural development, genes involved in language lateralization rather contribute to activity-dependent cognitive processes. Disease association analysis revealed associations of genes involved in Handedness with diseases affecting the whole body, while genes involved in language lateralization were specifically engaged in mental and neurological diseases. These findings further support the idea that Handedness and language lateralization are ontogenetically independent, complex phenotypes.
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left right axis differentiation and functional lateralization a haplotype in the methyltransferase encoding gene setdb2 might mediate Handedness in healthy adults
Molecular Neurobiology, 2016Co-Authors: Sebastian Ocklenburg, Wanda M Gerding, Larissa Arning, Joerg T Epplen, Onur Gunturkun, Jan G Hengstler, Denis A AkkadAbstract:Handedness is a multifactorial trait, and genes contributing to the differentiation of the left-right axis during embryogenesis have been identified as a major gene group associated with this trait. The methyltransferase SETDB2 (SET domain, bifurcated 2) has been shown to regulate structural left-right asymmetry in the vertebrate central nervous system by suppressing fgf8 expression. Here, we investigated the relation of genetic variation in SETDB2—and its paralogue SETDB1—with different Handedness phenotypes in 950 healthy adult participants. We identified a haplotype on SETDB2 for which homozygous individuals showed a significantly lower lateralization quotient for Handedness than the rest of the cohort after correction for multiple comparisons. Moreover, direction of Handedness was significantly associated with genetic variation in this haplotype. This effect was mainly, but not exclusively, driven by the sequence variation rs4942830, as individuals homozygous for the A allele of this single nucleotide polymorphism had a significantly lower lateralization quotient than individuals with at least one T allele. These findings further confirm a role of genetic pathways relevant for structural left-right axis differentiation for functional lateralization. Moreover, as the protein encoded by SETDB2 regulates gene expression epigenetically by histone H3 methylation, our findings highlight the importance of investigating the role of epigenetic modulations of gene expression in relation to Handedness.
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left right axis differentiation and functional lateralization a haplotype in the methyltransferase encoding gene setdb2 might mediate Handedness in healthy adults
Molecular Neurobiology, 2016Co-Authors: Sebastian Ocklenburg, Wanda M Gerding, Larissa Arning, Joerg T Epplen, Onur Gunturkun, Jan G Hengstler, Christian Beste, Denis A AkkadAbstract:Handedness is a multifactorial trait, and genes contributing to the differentiation of the left-right axis during embryogenesis have been identified as a major gene group associated with this trait. The methyltransferase SETDB2 (SET domain, bifurcated 2) has been shown to regulate structural left-right asymmetry in the vertebrate central nervous system by suppressing fgf8 expression. Here, we investigated the relation of genetic variation in SETDB2—and its paralogue SETDB1—with different Handedness phenotypes in 950 healthy adult participants. We identified a haplotype on SETDB2 for which homozygous individuals showed a significantly lower lateralization quotient for Handedness than the rest of the cohort after correction for multiple comparisons. Moreover, direction of Handedness was significantly associated with genetic variation in this haplotype. This effect was mainly, but not exclusively, driven by the sequence variation rs4942830, as individuals homozygous for the A allele of this single nucleotide polymorphism had a significantly lower lateralization quotient than individuals with at least one T allele. These findings further confirm a role of genetic pathways relevant for structural left-right axis differentiation for functional lateralization. Moreover, as the protein encoded by SETDB2 regulates gene expression epigenetically by histone H3 methylation, our findings highlight the importance of investigating the role of epigenetic modulations of gene expression in relation to Handedness.
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Handedness and the x chromosome the role of androgen receptor cag repeat length
Scientific Reports, 2015Co-Authors: Larissa Arning, Wanda M Gerding, Sebastian Ocklenburg, Joerg T Epplen, Onur Gunturkun, Jan G Hengstler, Stefanie Schulz, Vanessa Ness, Michael Falkenstein, Christian BesteAbstract:Prenatal androgen exposure has been suggested to be one of the factors influencing Handedness, making the androgen receptor gene (AR) a likely candidate gene for individual differences in Handedness. Here, we examined the relationship between the length of the CAG-repeat in AR and different Handedness phenotypes in a sample of healthy adults of both sexes (n = 1057). Since AR is located on the X chromosome, statistical analyses in women heterozygous for CAG-repeat lengths are complicated by X chromosome inactivation. We thus analyzed a sample of women that were homozygous for the CAG-repeat length (n = 77). Mixed-Handedness in men was significantly associated with longer CAG-repeat blocks and women homozygous for longer CAG-repeats showed a tendency for stronger left-Handedness. These results suggest that Handedness in both sexes is associated with the AR CAG-repeat length, with longer repeats being related to a higher incidence of non-right-Handedness. Since longer CAG-repeat blocks have been linked to less efficient AR function, these results implicate that differences in AR signaling in the developing brain might be one of the factors that determine individual differences in brain lateralization.
Stefan Knecht - One of the best experts on this subject based on the ideXlab platform.
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the association between scalp hair whorl direction Handedness and hemispheric language dominance is there a common genetic basis of lateralization
NeuroImage, 2007Co-Authors: Andreas Jansen, Hubertus Lohmann, Michael Deppe, Stefanie Scharfe, Christina Sehlmeyer, Stefan KnechtAbstract:The hemispheres of the human brain are functionally asymmetric. The left hemisphere tends to be dominant for language and superior in the control of manual dexterity. The mechanisms underlying these asymmetries are not known. Genetic as well as environmental factors are discussed. Recently, atypical anticlockwise hair-whorl direction has been related to an increased probability for non-right-Handedness and atypical hemispheric language dominance. These findings are fascinating and important since hair-whorl direction is a structural marker of lateralization and could provide a readily observable anatomical clue to functional brain lateralization. Based on data on Handedness and hair-whorl direction, Amar Klar proposed a genetic model ("random-recessive model") in that a single gene with two alleles controls both Handedness and hair-whorl orientation (Klar, A.J.S., 2003. Human Handedness and scalp hair-whorl direction develop from a common genetic mechanism. Genetics 165, 269-276). The present study was designed to further investigate the relationship between scalp hair-whorl direction with Handedness and hemispheric language dominance. 1212 subjects were investigated for scalp hair-whorl direction and Handedness. Additionally, we determined hemispheric language dominance (as assessed by a word generation task) in a subgroup of 212 subjects using functional transcranial Doppler sonography (fTCD). As for the single attributes - hair-whorl direction, Handedness, and language dominance - we reproduced previously published results. However, we found no association between hair-whorl direction and either language dominance or Handedness. These results strongly argue against a common genetic basis of Handedness or language lateralization with scalp hair-whorl direction. Inspection of hair patterns will not help us to determine language dominance.
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Handedness and hemispheric language dominance in healthy humans
Brain, 2000Co-Authors: Stefan Knecht, Bianca Drager, L Bobe, Hubertus Lohmann, Michael Deppe, E B Ringelstein, Agnes Floel, Henning HenningsenAbstract:In most people the left hemisphere of the brain is dominant for language. Because of the increased incidence of atypical right-hemispheric language in left-handed neurological patients, a systematic association between Handedness and dominance has long been suspected. To clarify the relationship between Handedness and language dominance in healthy subjects, we measured lateralization directly by functional transcranial Doppler sonography in 326 healthy individuals using a word-generation task. The incidence of right-hemisphere language dominance was found to increase linearly with the degree of left-Handedness, from 4% in strong right-handers (Handedness = 100) to 15% in ambidextrous individuals and 27% in strong left-handers (Handedness = -100). The relationship could be approximated by the formula: f1.gif" BORDER="0">. These results clearly demonstrate that the relationship between Handedness and language dominance is not an artefact of cerebral pathology but a natural phenomenon.
