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Ian J. Deary - One of the best experts on this subject based on the ideXlab platform.
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genetic stratification of depression by Neuroticism revisiting a diagnostic tradition
Psychological Medicine, 2020Co-Authors: Mark J Adams, Ian J. Deary, Michelle Luciano, Gail Davies, Toni-kim Clarke, David W Hill, David J Porteous, Daniel J Smith, David M Howard, Andrew M McintoshAbstract:Background. Major depressive disorder and Neuroticism share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression. Methods. We analysed summary statistics from genome-wide association studies of depression (from the Psychiatric Genomics Consortium, 23andMe, and UK Biobank) and compared them to genome-wide association studies (GWAS) of Neuroticism (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only Neuroticism, or with both. Second, we estimated partial genetic correlations to test whether the depression’s genetic link with other phenotypes was explained by shared overlap with Neuroticism. Results. We found evidence that most genomic regions (25/37) associated with depression are likely to be shared with Neuroticism. The overlapping common genetic variance of depression and Neuroticism was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that was not shared with Neuroticism, was positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with Neuroticism, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease, and age of first birth. Independent of depression, Neuroticism had specific genetic correlates in ulcerative colitis, pubertal growth, anorexia, and education. Conclusion. Our findings demonstrate that, while genetic risk factors for depression are largely shared with Neuroticism, there are also non-Neuroticism related features of depression that may be useful for further patient or phenotypic stratification.
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genetic contribution to two factors of Neuroticism is associated with affluence better health and longer life
bioRxiv, 2017Co-Authors: W D Hill, Andrew M Mcintosh, Alexander Weiss, Catharine R Gale, Ian J. DearyAbstract:Neuroticism is a personality trait that describes the tendency to experience negative emotions. Individual differences in Neuroticism are moderately stable across much of the life course; the trait is heritable, and higher levels are associated with psychiatric disorders, and have been estimated to have an economic burden to society greater than that of substance abuse, mood, or anxiety disorders. Understanding the genetic architecture of Neuroticism therefore has the potential to offer insight into the causes of psychiatric disorders, general wellbeing, and longevity. The broad trait of Neuroticism is composed of narrower traits, or factors. It was recently discovered that, whereas higher scores on the broad trait of Neuroticism are associated with earlier death, higher scores on a worry/vulnerability factor are associated with living longer. Here, we examine the genetic architectures of two Neuroticism factors, worry/vulnerability and anxiety/tension, and how they contrast with the architecture of the general factor of Neuroticism. We show that, whereas the polygenic load for general factor of Neuroticism is associated with an increased risk of coronary artery disease (CAD), major depressive disorder, and poorer self-rated health, the genetic variants associated with high levels of the anxiety/tension and worry/vulnerability factors are associated with affluence, higher cognitive ability, better self-rated health, and longer life. We also identify the first genes associated with factors of Neuroticism that are linked with these positive outcomes that show no relationship with the general factor of Neuroticism.
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intelligence and Neuroticism in relation to depression and psychological distress evidence from two large population cohorts
European Psychiatry, 2017Co-Authors: Lauren Navrady, Ian J. Deary, David J Porteous, Stuart J Ritchie, Stella Wy Chan, Mark J Adams, Emma L Hawkins, D KerrAbstract:Abstract Background Neuroticism is a risk factor for selected mental and physical illnesses and is inversely associated with intelligence. Intelligence appears to interact with Neuroticism and mitigate its detrimental effects on physical health and mortality. However, the inter-relationships of Neuroticism and intelligence for major depressive disorder (MDD) and psychological distress has not been well examined. Methods Associations and interactions between Neuroticism and general intelligence ( g ) on MDD, self-reported depression, and psychological distress were examined in two population-based cohorts: Generation Scotland: Scottish Family Health Study (GS:SFHS, n =19,200) and UK Biobank ( n =90,529). The Eysenck Personality Scale Short Form-Revised measured Neuroticism and g was extracted from multiple cognitive ability tests in each cohort. Family structure was adjusted for in GS:SFHS. Results Neuroticism was strongly associated with increased risk for depression and higher psychological distress in both samples. Although intelligence conferred no consistent independent effects on depression, it did increase the risk for depression across samples once Neuroticism was adjusted for. Results suggest that higher intelligence may ameliorate the association between Neuroticism and self-reported depression although no significant interaction was found for clinical MDD. Intelligence was inversely associated with psychological distress across cohorts. A small interaction was found across samples such that lower psychological distress associates with higher intelligence and lower Neuroticism, although effect sizes were small. Conclusions From two large cohort studies, our findings suggest intelligence acts a protective factor in mitigating the effects of Neuroticism on psychological distress. Intelligence does not confer protection against diagnosis of depression in those high in Neuroticism.
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intelligence and Neuroticism in relation to depression and psychological distress evidence of interaction using data from generation scotland scottish family health study and uk biobank
bioRxiv, 2016Co-Authors: Lauren Navrady, Ian J. Deary, David J Porteous, Stuart J Ritchie, Stella Wy Chan, Daniel M Kerr, Mark J Adams, Emma L Hawkins, C R Gale, David BattyAbstract:Background Neuroticism is a risk factor for selected mental and physical illnesses and is inversely associated with intelligence. Intelligence appears to interact with Neuroticism and mitigate its detrimental effects on physical health and mortality. However, the inter-ralationships of Neuroticism and intelligence for major depressive disorder (MDD) and psychological distress has not been well examined. Methods Associations and interactions between Neuroticism and general intelligence (g) on MDD and psychological distress were examined in two population-based cohorts: Generation Scotland: Scottish Family Health Study (GS:SFHS, N=19,200) and UK Biobank (N=90,529). The Eysenck Personality Scale Short Form-Revised measured Neuroticism and g was extracted from multiple cognitive ability tests in each cohort. Family structure was adjusted for in GS:SFHS. Results Neuroticism was associated with MDD and psychological distress in both samples. A significant interaction between Neuroticism and g in predicting MDD status was found in UK Biobank (OR = 0.96, p < .01), suggesting that higher g ameliorated the adverse effects of Neuroticism on the likelihood of having MDD. This interaction was not found in GS:SFHS. In both samples, higher Neuroticism and lower intelligence were associated with increased psychological distress. A significant interaction was also found in both cohorts (GS:SFHS: β = -0.05, p < .01; UK Biobank: β = -0.02, p < .01), such that intelligence protected against the deleterious effect of Neuroticism on psychological distress. Conclusions From two large cohort studies, our findings suggest intelligence acts a protective factor in mitigating the effects of Neuroticism on risk for depressive illness and psychological distress.
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pleiotropy between Neuroticism and physical and mental health findings from 108 038 men and women in uk biobank
bioRxiv, 2015Co-Authors: Catharine R Gale, Saskia P. Hagenaars, Gail Davies, David C. Liewald, David W Hill, Andrew M Mcintosh, Daniel J Smith, Breda Cullen, Jill P Pell, Ian J. DearyAbstract:There is considerable evidence that people with higher levels of the personality trait Neuroticism have an increased risk of several types of mental disorder. Higher Neuroticism has also been associated, less consistently, with increased risk of various physical health outcomes. We hypothesised that these associations may, in part, be due to shared genetic influences. We tested for pleiotropy between Neuroticism and 12 mental and physical diseases or health traits using linkage disequilibrium regression and polygenic profile scoring. Genetic correlations were derived between Neuroticism scores in 108 038 people in UK Biobank and health-related measures from 12 large genome-wide association studies(GWAS). Summary information for the 12 GWAS was used to create polygenic risk scores for the health-related measures in the UK Biobank participants. Associations between the health-related polygenic scores and Neuroticism were examined using regression, adjusting for age, sex, genotyping batch, genotyping array, assessment centre, and population stratification. Genetic correlations were identified between Neuroticism and anorexia nervosa(rg = 0.17), major depressive disorder (rg = 0.66) and schizophrenia (rg = 0.21). Polygenic risk for several health-related measures were associated with Neuroticism, in a positive direction in the case of bipolar disorder (β = 0.017), major depressive disorder (β = 0.036), schizophrenia (β = 0.036), and coronary artery disease (β = 0.011), and in a negative direction in the case of BMI (β = -0.0095). These findings indicate that a high level of pleiotropy exists between Neuroticism and some measures of mental and physical health, particularly major depressive disorder and schizophrenia.
Catharine R Gale - One of the best experts on this subject based on the ideXlab platform.
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genetic contributions to two special factors of Neuroticism are associated with affluence higher intelligence better health and longer life
Molecular Psychiatry, 2020Co-Authors: David W Hill, Gail Davies, David C. Liewald, Alexander Weiss, David J Porteous, Caroline Hayward, Andrew M Mcintosh, Catharine R GaleAbstract:Higher scores on the personality trait of Neuroticism, the tendency to experience negative emotions, are associated with worse mental and physical health. Studies examining links between Neuroticism and health typically operationalize Neuroticism by summing the items from a Neuroticism scale. However, Neuroticism is made up of multiple heterogeneous facets, each contributing to the effect of Neuroticism as a whole. A recent study showed that a 12-item Neuroticism scale described one broad trait of general Neuroticism and two special factors, one characterizing the extent to which people worry and feel vulnerable, and the other characterizing the extent to which people are anxious and tense. This study also found that, although individuals who were higher on general Neuroticism lived shorter lives, individuals whose Neuroticism was characterized by worry and vulnerability lived longer lives. Here, we examine the genetic contributions to the two special factors of Neuroticism—anxiety/tension and worry/vulnerability—and how they contrast with that of general Neuroticism. First, we show that, whereas the polygenic load for Neuroticism is associated with the genetic risk of coronary artery disease, lower intelligence, lower socioeconomic status (SES), and poorer self-rated health, the genetic variants associated with high levels of anxiety/tension, and high levels of worry/vulnerability are associated with genetic variants linked to higher SES, higher intelligence, better self-rated health, and longer life. Second, we identify genetic variants that are uniquely associated with these protective aspects of Neuroticism. Finally, we show that different neurological pathways are linked to each of these Neuroticism phenotypes.
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genetic contribution to two factors of Neuroticism is associated with affluence better health and longer life
bioRxiv, 2017Co-Authors: W D Hill, Andrew M Mcintosh, Alexander Weiss, Catharine R Gale, Ian J. DearyAbstract:Neuroticism is a personality trait that describes the tendency to experience negative emotions. Individual differences in Neuroticism are moderately stable across much of the life course; the trait is heritable, and higher levels are associated with psychiatric disorders, and have been estimated to have an economic burden to society greater than that of substance abuse, mood, or anxiety disorders. Understanding the genetic architecture of Neuroticism therefore has the potential to offer insight into the causes of psychiatric disorders, general wellbeing, and longevity. The broad trait of Neuroticism is composed of narrower traits, or factors. It was recently discovered that, whereas higher scores on the broad trait of Neuroticism are associated with earlier death, higher scores on a worry/vulnerability factor are associated with living longer. Here, we examine the genetic architectures of two Neuroticism factors, worry/vulnerability and anxiety/tension, and how they contrast with the architecture of the general factor of Neuroticism. We show that, whereas the polygenic load for general factor of Neuroticism is associated with an increased risk of coronary artery disease (CAD), major depressive disorder, and poorer self-rated health, the genetic variants associated with high levels of the anxiety/tension and worry/vulnerability factors are associated with affluence, higher cognitive ability, better self-rated health, and longer life. We also identify the first genes associated with factors of Neuroticism that are linked with these positive outcomes that show no relationship with the general factor of Neuroticism.
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pleiotropy between Neuroticism and physical and mental health findings from 108 038 men and women in uk biobank
Translational Psychiatry, 2016Co-Authors: Saskia P. Hagenaars, Gail Davies, David C. Liewald, David W Hill, Catharine R Gale, Breda Cullen, B W J H Penninx, Dorret I Boomsma, Jill P PellAbstract:People with higher levels of Neuroticism have an increased risk of several types of mental disorder. Higher Neuroticism has also been associated, less consistently, with increased risk of various physical health outcomes. We hypothesised that these associations may, in part, be due to shared genetic influences. We tested for pleiotropy between Neuroticism and 17 mental and physical diseases or health traits using linkage disequilibrium regression and polygenic profile scoring. Genetic correlations were derived between Neuroticism scores in 108 038 people in the UK Biobank and health-related measures from 14 large genome-wide association studies (GWASs). Summary information for the 17 GWASs was used to create polygenic risk scores for the health-related measures in the UK Biobank participants. Associations between the health-related polygenic scores and Neuroticism were examined using regression, adjusting for age, sex, genotyping batch, genotyping array, assessment centre and population stratification. Genetic correlations were identified between Neuroticism and anorexia nervosa (rg=0.17), major depressive disorder (rg=0.66) and schizophrenia (rg=0.21). Polygenic risk for several health-related measures were associated with Neuroticism, in a positive direction in the case of bipolar disorder, borderline personality, major depressive disorder, negative affect, Neuroticism (Genetics of Personality Consortium), schizophrenia, coronary artery disease, and smoking (β between 0.009–0.043), and in a negative direction in the case of body mass index (β=−0.0095). A high level of pleiotropy exists between Neuroticism and some measures of mental and physical health, particularly major depressive disorder and schizophrenia.
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pleiotropy between Neuroticism and physical and mental health findings from 108 038 men and women in uk biobank
bioRxiv, 2015Co-Authors: Catharine R Gale, Saskia P. Hagenaars, Gail Davies, David C. Liewald, David W Hill, Andrew M Mcintosh, Daniel J Smith, Breda Cullen, Jill P Pell, Ian J. DearyAbstract:There is considerable evidence that people with higher levels of the personality trait Neuroticism have an increased risk of several types of mental disorder. Higher Neuroticism has also been associated, less consistently, with increased risk of various physical health outcomes. We hypothesised that these associations may, in part, be due to shared genetic influences. We tested for pleiotropy between Neuroticism and 12 mental and physical diseases or health traits using linkage disequilibrium regression and polygenic profile scoring. Genetic correlations were derived between Neuroticism scores in 108 038 people in UK Biobank and health-related measures from 12 large genome-wide association studies(GWAS). Summary information for the 12 GWAS was used to create polygenic risk scores for the health-related measures in the UK Biobank participants. Associations between the health-related polygenic scores and Neuroticism were examined using regression, adjusting for age, sex, genotyping batch, genotyping array, assessment centre, and population stratification. Genetic correlations were identified between Neuroticism and anorexia nervosa(rg = 0.17), major depressive disorder (rg = 0.66) and schizophrenia (rg = 0.21). Polygenic risk for several health-related measures were associated with Neuroticism, in a positive direction in the case of bipolar disorder (β = 0.017), major depressive disorder (β = 0.036), schizophrenia (β = 0.036), and coronary artery disease (β = 0.011), and in a negative direction in the case of BMI (β = -0.0095). These findings indicate that a high level of pleiotropy exists between Neuroticism and some measures of mental and physical health, particularly major depressive disorder and schizophrenia.
Gail Davies - One of the best experts on this subject based on the ideXlab platform.
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genetic stratification of depression by Neuroticism revisiting a diagnostic tradition
Psychological Medicine, 2020Co-Authors: Mark J Adams, Ian J. Deary, Michelle Luciano, Gail Davies, Toni-kim Clarke, David W Hill, David J Porteous, Daniel J Smith, David M Howard, Andrew M McintoshAbstract:Background. Major depressive disorder and Neuroticism share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression. Methods. We analysed summary statistics from genome-wide association studies of depression (from the Psychiatric Genomics Consortium, 23andMe, and UK Biobank) and compared them to genome-wide association studies (GWAS) of Neuroticism (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only Neuroticism, or with both. Second, we estimated partial genetic correlations to test whether the depression’s genetic link with other phenotypes was explained by shared overlap with Neuroticism. Results. We found evidence that most genomic regions (25/37) associated with depression are likely to be shared with Neuroticism. The overlapping common genetic variance of depression and Neuroticism was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that was not shared with Neuroticism, was positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with Neuroticism, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease, and age of first birth. Independent of depression, Neuroticism had specific genetic correlates in ulcerative colitis, pubertal growth, anorexia, and education. Conclusion. Our findings demonstrate that, while genetic risk factors for depression are largely shared with Neuroticism, there are also non-Neuroticism related features of depression that may be useful for further patient or phenotypic stratification.
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genetic contributions to two special factors of Neuroticism are associated with affluence higher intelligence better health and longer life
Molecular Psychiatry, 2020Co-Authors: David W Hill, Gail Davies, David C. Liewald, Alexander Weiss, David J Porteous, Caroline Hayward, Andrew M Mcintosh, Catharine R GaleAbstract:Higher scores on the personality trait of Neuroticism, the tendency to experience negative emotions, are associated with worse mental and physical health. Studies examining links between Neuroticism and health typically operationalize Neuroticism by summing the items from a Neuroticism scale. However, Neuroticism is made up of multiple heterogeneous facets, each contributing to the effect of Neuroticism as a whole. A recent study showed that a 12-item Neuroticism scale described one broad trait of general Neuroticism and two special factors, one characterizing the extent to which people worry and feel vulnerable, and the other characterizing the extent to which people are anxious and tense. This study also found that, although individuals who were higher on general Neuroticism lived shorter lives, individuals whose Neuroticism was characterized by worry and vulnerability lived longer lives. Here, we examine the genetic contributions to the two special factors of Neuroticism—anxiety/tension and worry/vulnerability—and how they contrast with that of general Neuroticism. First, we show that, whereas the polygenic load for Neuroticism is associated with the genetic risk of coronary artery disease, lower intelligence, lower socioeconomic status (SES), and poorer self-rated health, the genetic variants associated with high levels of anxiety/tension, and high levels of worry/vulnerability are associated with genetic variants linked to higher SES, higher intelligence, better self-rated health, and longer life. Second, we identify genetic variants that are uniquely associated with these protective aspects of Neuroticism. Finally, we show that different neurological pathways are linked to each of these Neuroticism phenotypes.
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association analysis in over 329 000 individuals identifies 116 independent variants influencing Neuroticism
Nature Genetics, 2018Co-Authors: Michelle Luciano, Saskia P. Hagenaars, Gail Davies, Toni-kim Clarke, Masoud Shirali, Sarah E. Harris, David W Hill, Riccardo E. MarioniAbstract:Neuroticism is a relatively stable personality trait characterized by negative emotionality (for example, worry and guilt)1; heritability estimated from twin studies ranges from 30 to 50%2, and SNP-based heritability ranges from 6 to 15%3–6. Increased Neuroticism is associated with poorer mental and physical health7,8, translating to high economic burden9. Genome-wide association studies (GWAS) of Neuroticism have identified up to 11 associated genetic loci3,4. Here we report 116 significant independent loci from a GWAS of Neuroticism in 329,821 UK Biobank participants; 15 of these loci replicated at P < 0.00045 in an unrelated cohort (N = 122,867). Genetic signals were enriched in neuronal genesis and differentiation pathways, and substantial genetic correlations were found between Neuroticism and depressive symptoms (rg = 0.82, standard error (s.e.) = 0.03), major depressive disorder (MDD; rg = 0.69, s.e. = 0.07) and subjective well-being (rg = –0.68, s.e. = 0.03) alongside other mental health traits. These discoveries significantly advance understanding of Neuroticism and its association with MDD. Analysis of 329,000 individuals in the UK Biobank identifies 116 loci associated with Neuroticism. Genes implicated are enriched in neuronal differentiation pathways, and genetic correlations between Neuroticism and other mental health traits are elucidated.
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116 independent genetic variants influence the Neuroticism personality trait in over 329,000 UK Biobank individuals.
2017Co-Authors: Michelle Luciano, Saskia P. Hagenaars, Gail Davies, W. David Hill, Toni-kim Clarke, Masoud Shirali, Riccardo E. Marioni, Sarah E. Harris, David C. Liewald, Chloe Fawns-ritchieAbstract:Neuroticism is a stable personality trait; twin studies report heritability between 30% and 50%, and SNP-based heritability is about 15%. Higher levels of Neuroticism are associated with poorer mental and physical health, and the economic burden of Neuroticism for societies is high. To date, genome-wide association (GWA) studies of Neuroticism have identified up to 11 genetic loci. Here we report 116 significant independent genetic loci from a GWA of Neuroticism in 329,821 UK Biobank participants, with replication available in a GWA meta-analysis of Neuroticism in 122,867 individuals. Genetic signals for Neuroticism were enriched in neuronal genesis and differentiation pathways, and substantial genetic correlations were found between Neuroticism and depressive symptoms (rg = .82, SE=.03), major depressive disorder (rg = .69, SE=.07) and subjective wellbeing (rg = -.68, SE=.03) alongside other mental health traits. These discoveries significantly advance our understanding of Neuroticism and its association with major depressive disorder.
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pleiotropy between Neuroticism and physical and mental health findings from 108 038 men and women in uk biobank
Translational Psychiatry, 2016Co-Authors: Saskia P. Hagenaars, Gail Davies, David C. Liewald, David W Hill, Catharine R Gale, Breda Cullen, B W J H Penninx, Dorret I Boomsma, Jill P PellAbstract:People with higher levels of Neuroticism have an increased risk of several types of mental disorder. Higher Neuroticism has also been associated, less consistently, with increased risk of various physical health outcomes. We hypothesised that these associations may, in part, be due to shared genetic influences. We tested for pleiotropy between Neuroticism and 17 mental and physical diseases or health traits using linkage disequilibrium regression and polygenic profile scoring. Genetic correlations were derived between Neuroticism scores in 108 038 people in the UK Biobank and health-related measures from 14 large genome-wide association studies (GWASs). Summary information for the 17 GWASs was used to create polygenic risk scores for the health-related measures in the UK Biobank participants. Associations between the health-related polygenic scores and Neuroticism were examined using regression, adjusting for age, sex, genotyping batch, genotyping array, assessment centre and population stratification. Genetic correlations were identified between Neuroticism and anorexia nervosa (rg=0.17), major depressive disorder (rg=0.66) and schizophrenia (rg=0.21). Polygenic risk for several health-related measures were associated with Neuroticism, in a positive direction in the case of bipolar disorder, borderline personality, major depressive disorder, negative affect, Neuroticism (Genetics of Personality Consortium), schizophrenia, coronary artery disease, and smoking (β between 0.009–0.043), and in a negative direction in the case of body mass index (β=−0.0095). A high level of pleiotropy exists between Neuroticism and some measures of mental and physical health, particularly major depressive disorder and schizophrenia.
David W Hill - One of the best experts on this subject based on the ideXlab platform.
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genetic stratification of depression by Neuroticism revisiting a diagnostic tradition
Psychological Medicine, 2020Co-Authors: Mark J Adams, Ian J. Deary, Michelle Luciano, Gail Davies, Toni-kim Clarke, David W Hill, David J Porteous, Daniel J Smith, David M Howard, Andrew M McintoshAbstract:Background. Major depressive disorder and Neuroticism share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression. Methods. We analysed summary statistics from genome-wide association studies of depression (from the Psychiatric Genomics Consortium, 23andMe, and UK Biobank) and compared them to genome-wide association studies (GWAS) of Neuroticism (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only Neuroticism, or with both. Second, we estimated partial genetic correlations to test whether the depression’s genetic link with other phenotypes was explained by shared overlap with Neuroticism. Results. We found evidence that most genomic regions (25/37) associated with depression are likely to be shared with Neuroticism. The overlapping common genetic variance of depression and Neuroticism was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that was not shared with Neuroticism, was positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with Neuroticism, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease, and age of first birth. Independent of depression, Neuroticism had specific genetic correlates in ulcerative colitis, pubertal growth, anorexia, and education. Conclusion. Our findings demonstrate that, while genetic risk factors for depression are largely shared with Neuroticism, there are also non-Neuroticism related features of depression that may be useful for further patient or phenotypic stratification.
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genetic contributions to two special factors of Neuroticism are associated with affluence higher intelligence better health and longer life
Molecular Psychiatry, 2020Co-Authors: David W Hill, Gail Davies, David C. Liewald, Alexander Weiss, David J Porteous, Caroline Hayward, Andrew M Mcintosh, Catharine R GaleAbstract:Higher scores on the personality trait of Neuroticism, the tendency to experience negative emotions, are associated with worse mental and physical health. Studies examining links between Neuroticism and health typically operationalize Neuroticism by summing the items from a Neuroticism scale. However, Neuroticism is made up of multiple heterogeneous facets, each contributing to the effect of Neuroticism as a whole. A recent study showed that a 12-item Neuroticism scale described one broad trait of general Neuroticism and two special factors, one characterizing the extent to which people worry and feel vulnerable, and the other characterizing the extent to which people are anxious and tense. This study also found that, although individuals who were higher on general Neuroticism lived shorter lives, individuals whose Neuroticism was characterized by worry and vulnerability lived longer lives. Here, we examine the genetic contributions to the two special factors of Neuroticism—anxiety/tension and worry/vulnerability—and how they contrast with that of general Neuroticism. First, we show that, whereas the polygenic load for Neuroticism is associated with the genetic risk of coronary artery disease, lower intelligence, lower socioeconomic status (SES), and poorer self-rated health, the genetic variants associated with high levels of anxiety/tension, and high levels of worry/vulnerability are associated with genetic variants linked to higher SES, higher intelligence, better self-rated health, and longer life. Second, we identify genetic variants that are uniquely associated with these protective aspects of Neuroticism. Finally, we show that different neurological pathways are linked to each of these Neuroticism phenotypes.
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association analysis in over 329 000 individuals identifies 116 independent variants influencing Neuroticism
Nature Genetics, 2018Co-Authors: Michelle Luciano, Saskia P. Hagenaars, Gail Davies, Toni-kim Clarke, Masoud Shirali, Sarah E. Harris, David W Hill, Riccardo E. MarioniAbstract:Neuroticism is a relatively stable personality trait characterized by negative emotionality (for example, worry and guilt)1; heritability estimated from twin studies ranges from 30 to 50%2, and SNP-based heritability ranges from 6 to 15%3–6. Increased Neuroticism is associated with poorer mental and physical health7,8, translating to high economic burden9. Genome-wide association studies (GWAS) of Neuroticism have identified up to 11 associated genetic loci3,4. Here we report 116 significant independent loci from a GWAS of Neuroticism in 329,821 UK Biobank participants; 15 of these loci replicated at P < 0.00045 in an unrelated cohort (N = 122,867). Genetic signals were enriched in neuronal genesis and differentiation pathways, and substantial genetic correlations were found between Neuroticism and depressive symptoms (rg = 0.82, standard error (s.e.) = 0.03), major depressive disorder (MDD; rg = 0.69, s.e. = 0.07) and subjective well-being (rg = –0.68, s.e. = 0.03) alongside other mental health traits. These discoveries significantly advance understanding of Neuroticism and its association with MDD. Analysis of 329,000 individuals in the UK Biobank identifies 116 loci associated with Neuroticism. Genes implicated are enriched in neuronal differentiation pathways, and genetic correlations between Neuroticism and other mental health traits are elucidated.
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pleiotropy between Neuroticism and physical and mental health findings from 108 038 men and women in uk biobank
Translational Psychiatry, 2016Co-Authors: Saskia P. Hagenaars, Gail Davies, David C. Liewald, David W Hill, Catharine R Gale, Breda Cullen, B W J H Penninx, Dorret I Boomsma, Jill P PellAbstract:People with higher levels of Neuroticism have an increased risk of several types of mental disorder. Higher Neuroticism has also been associated, less consistently, with increased risk of various physical health outcomes. We hypothesised that these associations may, in part, be due to shared genetic influences. We tested for pleiotropy between Neuroticism and 17 mental and physical diseases or health traits using linkage disequilibrium regression and polygenic profile scoring. Genetic correlations were derived between Neuroticism scores in 108 038 people in the UK Biobank and health-related measures from 14 large genome-wide association studies (GWASs). Summary information for the 17 GWASs was used to create polygenic risk scores for the health-related measures in the UK Biobank participants. Associations between the health-related polygenic scores and Neuroticism were examined using regression, adjusting for age, sex, genotyping batch, genotyping array, assessment centre and population stratification. Genetic correlations were identified between Neuroticism and anorexia nervosa (rg=0.17), major depressive disorder (rg=0.66) and schizophrenia (rg=0.21). Polygenic risk for several health-related measures were associated with Neuroticism, in a positive direction in the case of bipolar disorder, borderline personality, major depressive disorder, negative affect, Neuroticism (Genetics of Personality Consortium), schizophrenia, coronary artery disease, and smoking (β between 0.009–0.043), and in a negative direction in the case of body mass index (β=−0.0095). A high level of pleiotropy exists between Neuroticism and some measures of mental and physical health, particularly major depressive disorder and schizophrenia.
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pleiotropy between Neuroticism and physical and mental health findings from 108 038 men and women in uk biobank
bioRxiv, 2015Co-Authors: Catharine R Gale, Saskia P. Hagenaars, Gail Davies, David C. Liewald, David W Hill, Andrew M Mcintosh, Daniel J Smith, Breda Cullen, Jill P Pell, Ian J. DearyAbstract:There is considerable evidence that people with higher levels of the personality trait Neuroticism have an increased risk of several types of mental disorder. Higher Neuroticism has also been associated, less consistently, with increased risk of various physical health outcomes. We hypothesised that these associations may, in part, be due to shared genetic influences. We tested for pleiotropy between Neuroticism and 12 mental and physical diseases or health traits using linkage disequilibrium regression and polygenic profile scoring. Genetic correlations were derived between Neuroticism scores in 108 038 people in UK Biobank and health-related measures from 12 large genome-wide association studies(GWAS). Summary information for the 12 GWAS was used to create polygenic risk scores for the health-related measures in the UK Biobank participants. Associations between the health-related polygenic scores and Neuroticism were examined using regression, adjusting for age, sex, genotyping batch, genotyping array, assessment centre, and population stratification. Genetic correlations were identified between Neuroticism and anorexia nervosa(rg = 0.17), major depressive disorder (rg = 0.66) and schizophrenia (rg = 0.21). Polygenic risk for several health-related measures were associated with Neuroticism, in a positive direction in the case of bipolar disorder (β = 0.017), major depressive disorder (β = 0.036), schizophrenia (β = 0.036), and coronary artery disease (β = 0.011), and in a negative direction in the case of BMI (β = -0.0095). These findings indicate that a high level of pleiotropy exists between Neuroticism and some measures of mental and physical health, particularly major depressive disorder and schizophrenia.
Parra Alejandro - One of the best experts on this subject based on the ideXlab platform.
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Diferencias individuales en la frecuencia del recuerdo de sueños exóticos
Fundación Universitaria Konrad Lorenz. Production and hosting by Elsevier España S.L., 2014Co-Authors: Parra AlejandroAbstract:ResumenEl objetivo de este estudio es, por una parte, determinar las características de personalidad entre individuos que recuerdan sueños y, por otra, comparar las puntuaciones obtenidas en la alteración dormital, el Neuroticismo y la extroversión, y los indicadores de propensión a la esquizotipia en individuos que no recuerdan sueños. Para este fin, se examinó la frecuencia del recuerdo del sueño con contenido extraño, inusual, y anómalo-paranormal. Vale la pena resaltar que pocos estudios han explorado las diferencias individuales en relación con tales sueños. En este estudio se reagrupó una muestra de 231 individuos de ambos sexos que puntuaron su calidad en el recuerdo del sueño entre alta (n=57) y baja (n=174). Se emplearon tres instrumentos que miden la etapa dormital y dos que miden el Neuroticismo, la extroversión y la esquizotipia. Los sueños exóticos más frecuentes son los auditivos, los lúcidos, los recurrentes, los psíquicos y los asociados al recuerdo de personas fallecidas. Las puntuaciones altas en la alteración del sueño, las experiencias esquizotípicas y las experiencias hipnagógicas e hipnopómpicas caracterizan a los soñadores en comparación con los no soñadores. Este estudio sostiene la idea de que ciertos indicadores de propensión a la esquizotipia están asociados a la frecuencia del recuerdo de sueños exóticos.AbstractThis study aimed to assess personality traits amongst individuals who remember dreams, on the one hand, and to compare scores obtained in sleep disorder, Neuroticism and extroversion, as well as indicators of proneness to schizotypy in individuals who cannot remember dreams, on the other. To this end, dream recall frequency was assessed as including strange, unusual and anomalous/paranormal content. Notably, few studies have explored individual differences in such dreams. A sample of 231 men and women with high (n=57) and low (n=174) scores on dream recall quality was clustered in this study. Three instruments that measure sleep stage and two which measure Neuroticism, extroversion and schizotypy were used. The most common exotic dreams were auditory dreams, lucid dreams, recurring dreams, psychic dreams, and dreams associated with deceased persons. In comparison with non-dreamers, dreamers had higher scores for sleep disorder, schizotypal experiences, and hypnagogic/hypnopompic experiences. This study supports the idea that some indicators of proneness to schizotypy are associated with the frequency of exotic dream recall
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Diferencias individuales en la frecuencia del recuerdo de sueños exóticos
2014Co-Authors: Parra AlejandroAbstract:This study aimed to assess personality traits amongst individuals who remember dreams, on the one hand, and to compare scores obtained in sleep disorder, Neuroticism and extroversion, as well as indicators of proneness to schizotypy in individuals who cannot remember dreams, on the other. To this end, dream recall frequency was assessed as including strange, unusual and anomalous/paranormal content. Notably, few studies have explored individual differences in such dreams. A sample of 231 men and women with high (n=57) and low (n=174) scores on dream recall quality was clustered in this study. Three instruments that measure sleep stage and two which measure Neuroticism, extroversion and schizotypy were used. The most common exotic dreams were auditory dreams, lucid dreams, recurring dreams, psychic dreams, and dreams associated with deceased persons. In comparison with non-dreamers, dreamers had higher scores for sleep disorder, schizotypal experiences, and hypnagogic/hypnopompic experiences. This study supports the idea that some indicators of proneness to schizotypy are associated with the frequency of exotic dream recall.El objetivo de este estudio es, por una parte, determinar las características de personalidad entre individuos que recuerdan sueños y, por otra, comparar las puntuaciones obtenidas en la alteración dormital, el Neuroticismo y la extroversión, y los indicadores de propensión a la esquizotipia en individuos que no recuerdan sueños. Para este fin, se examinó la frecuencia del recuerdo del sueño con contenido extraño, inusual, y anómalo-paranormal. Vale la pena resaltar que pocos estudios han explorado las diferencias individuales en relación con tales sueños. En este estudio se reagrupó una muestra de 231 individuos de ambos sexos que puntuaron su calidad en el recuerdo del sueño entre alta (n = 57) y baja (n = 174). Se emplearon tres instrumentos que miden la etapa dormital y dos que miden el Neuroticismo, la extroversión y la esquizotipia. Los sueños exóticos más frecuentes son los auditivos, los lúcidos, los recurrentes, los psíquicos y los asociados al recuerdo de personas fallecidas. Las puntuaciones altas en la alteración del sueño, las experiencias esquizotípicas y las experiencias hipnagógicas e hipnopómpicas caracterizan a los soñadores en comparación con los no soñadores. Este estudio sostiene la idea de que ciertos indicadores de propensión a la esquizotipia están asociados a la frecuencia del recuerdo de sueños exóticos
