Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium : an application of Item Response Theory

Peer reviewe

Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion

Meta-analysis of genome-wide association studies for extraversion:Findings from the Genetics of Personality Consortium

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion

A generic drift reduction technique for orientation estimation from biomechanical angular velocity

Inertial measurement units are used in ambulatory human movement analysis, but their use is often subject to domain- or application-specific assumptions and methods to compensate for drift in kinematic estimations. Here, we propose and evaluate a generic drift reduction technique for orientation estimation. A second order Taylor approximation for 3D orientation estimation from sampled angular velocity is derived and evaluated on a publicly available dataset containing angular velocity data of 4 runners. The use of a second order Taylor approximation substantially reduces drift when the angular velocity has considerable contributions along all three axes. The second order Taylor approximation could therefore facilitate the use of minimal sensor setups for the study of dynamic 3D human movements

Estimation of vertical ground reaction forces and sagittal knee kinematics during running using three inertial sensors

Analysis of running mechanics has traditionally been limited to a gait laboratory using either force plates or an instrumented treadmill in combination with a full-body optical motion capture system. With the introduction of inertial motion capture systems, it becomes possible to measure kinematics in any environment. However, kinetic information could not be provided with such technology. Furthermore, numerous body-worn sensors are required for a full-body motion analysis. The aim of this study is to examine the validity of a method to estimate sagittal knee joint angles and vertical ground reaction forces during running using an ambulatory minimal body-worn sensor setup. Two concatenated artificial neural networks were trained (using data from eight healthy subjects) to estimate the kinematics and kinetics of the runners. The first artificial neural network maps the information (orientation and acceleration) of three inertial sensors (placed at the lower legs and pelvis) to lower-body joint angles. The estimated joint angles in combination with measured vertical accelerations are input to a second artificial neural network that estimates vertical ground reaction forces. To validate our approach, estimated joint angles were compared to both inertial and optical references, while kinetic output was compared to measured vertical ground reaction forces from an instrumented treadmill. Performance was evaluated using two scenarios: training and evaluating on a single subject and training on multiple subjects and evaluating on a different subject. The estimated kinematics and kinetics of most subjects show excellent agreement (ρ > 0.99) with the reference, for single subject training. Knee flexion/extension angles are estimated with a mean RMSE 0.9) is still achieved for seven of the eight different evaluated subjects. The performance of multiple subject learning depends on the diversity in the training dataset, as differences in accuracy were found for the different evaluated subjects

Estimation of Vertical Ground Reaction Forces and Sagittal Knee Kinematics During Running Using Three Inertial Sensors

Analysis of running mechanics has traditionally been limited to a gait laboratory using either force plates or an instrumented treadmill in combination with a full-body optical motion capture system. With the introduction of inertial motion capture systems, it becomes possible to measure kinematics in any environment. However, kinetic information could not be provided with such technology. Furthermore, numerous body-worn sensors are required for a full-body motion analysis. The aim of this study is to examine the validity of a method to estimate sagittal knee joint angles and vertical ground reaction forces during running using an ambulatory minimal body-worn sensor setup. Two concatenated artificial neural networks were trained (using data from eight healthy subjects) to estimate the kinematics and kinetics of the runners. The first artificial neural network maps the information (orientation and acceleration) of three inertial sensors (placed at the lower legs and pelvis) to lower-body joint angles. The estimated joint angles in combination with measured vertical accelerations are input to a second artificial neural network that estimates vertical ground reaction forces. To validate our approach, estimated joint angles were compared to both inertial and optical references, while kinetic output was compared to measured vertical ground reaction forces from an instrumented treadmill. Performance was evaluated using two scenarios: training and evaluating on a single subject and training on multiple subjects and evaluating on a different subject. The estimated kinematics and kinetics of most subjects show excellent agreement (ρ>0.99) with the reference, for single subject training. Knee flexion/extension angles are estimated with a mean RMSE <5°. Ground reaction forces are estimated with a mean RMSE < 0.27 BW. Additionaly, peak vertical ground reaction force, loading rate and maximal knee flexion during stance were compared, however, no significant differences were found. With multiple subject training the accuracy of estimating discrete and continuous outcomes decreases, however, good agreement (ρ > 0.9) is still achieved for seven of the eight different evaluated subjects. The performance of multiple subject learning depends on the diversity in the training dataset, as differences in accuracy were found for the different evaluated subjects

Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder

Abstract IMPORTANCE: Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63 000 participants (including MDD cases). OBJECTIVES: To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS: Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63 661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES: Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS: A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10-12 < P < .05) and MDD (4.02 × 10-9 < P < .05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE: This study identifies a novel locus for neuroticism. The variant is located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies. In addition, the study shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagged by common variants. These genetic variants also influence MDD. Future studies should confirm the role of the MAGI1 locus for neuroticism and further investigate the association of MAGI1 and the polygenic association to a range of other psychiatric disorders that are phenotypically correlated with neuroticism

Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion

Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion

Meta-analysis of genome-wide association studies for neuroticism, and the polygenic association with major depressive disorder

IMPORTANCE Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63 000 participants (including MDD cases). OBJECTIVES To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63 661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10-8). Common genetic variants explain 15%of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10-12 -9 < P < .05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE This study identifies a novel locus for neuroticism. The variant is located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies. In addition, the study shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagge