Genome-wide analysis of self-reported risk-taking behaviour and cross-disorder genetic correlations in the UK Biobank cohort

AbstractRisk-taking behaviour is a key component of several psychiatric disorders and could influence lifestyle choices such as smoking, alcohol use and diet. As a phenotype, risk-taking behaviour therefore fits within a Research Domain Criteria (RDoC) approach, whereby identifying genetic determinants of this trait has the potential to improve our understanding across different psychiatric disorders. Here we report a genome wide association study in 116 255 UK Biobank participants who responded yes/no to the question “Would you consider yourself a risk-taker?” Risk-takers (compared to controls) were more likely to be men, smokers and have a history of psychiatric disorder. Genetic loci associated with risk-taking behaviour were identified on chromosomes 3 (rs13084531) and 6 (rs9379971). The effects of both lead SNPs were comparable between men and women. The chromosome 3 locus highlights CADM2, previously implicated in cognitive and executive functions, but the chromosome 6 locus is challenging to interpret due to the complexity of the HLA region. Risk-taking behaviour shared significant genetic risk with schizophrenia, bipolar disorder, attention deficit hyperactivity disorder and post-traumatic stress disorder, as well as with smoking and total obesity. Despite being based on only a single question, this study furthers our understanding of the biology of risk-taking behaviour, a trait which has a major impact on a range of common physical and mental health disorders.

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Genome-wide analyses of behavioural traits are subject to bias by misreports and longitudinal changes

Nature Communications ◽

10.1038/s41467-020-20237-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Angli Xue ◽

Longda Jiang ◽

Zhihong Zhu ◽

Naomi R. Wray ◽

Peter M. Visscher ◽

...

Keyword(s):

Alcohol Consumption ◽

Association Studies ◽

Genetic Correlations ◽

Genome Wide Association Studies ◽

Uk Biobank ◽

Longitudinal Changes ◽

Genome Wide ◽

The Uk ◽

Almost All ◽

Cardiovascular Traits

AbstractGenome-wide association studies (GWAS) have discovered numerous genetic variants associated with human behavioural traits. However, behavioural traits are subject to misreports and longitudinal changes (MLC) which can cause biases in GWAS and follow-up analyses. Here, we demonstrate that individuals with higher disease burden in the UK Biobank (n = 455,607) are more likely to misreport or reduce their alcohol consumption levels, and propose a correction procedure to mitigate the MLC-induced biases. The alcohol consumption GWAS signals removed by the MLC corrections are enriched in metabolic/cardiovascular traits. Almost all the previously reported negative estimates of genetic correlations between alcohol consumption and common diseases become positive/non-significant after the MLC corrections. We also observe MLC biases for smoking and physical activities in the UK Biobank. Our findings provide a plausible explanation of the controversy about the effects of alcohol consumption on health outcomes and a caution for future analyses of self-reported behavioural traits in biobank data.

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Genome-wide gene-environment analyses of depression and reported lifetime traumatic experiences in UK Biobank

10.1101/247353 ◽

2018 ◽

Cited By ~ 10

Author(s):

Jonathan R.I. Coleman ◽

Kirstin L. Purves ◽

Katrina A.S. Davis ◽

Christopher Rayner ◽

Shing Wan Choi ◽

...

Keyword(s):

Genetic Correlations ◽

Trauma Exposure ◽

Endogenous Depression ◽

European Ancestry ◽

Traumatic Experiences ◽

Uk Biobank ◽

Gene Environment ◽

Genome Wide ◽

Final Sample ◽

The Uk

AbstractDepression is more frequently observed among individuals exposed to traumatic events. The relationship between trauma exposure and depression, including the role of genetic variation, is complex and poorly understood. The UK Biobank concurrently assessed depression and reported trauma exposure in 126,522 genotyped individuals of European ancestry. We compared the shared aetiology of depression and a range of phenotypes, contrasting individuals reporting trauma exposure with those who did not (final sample size range: 24,094-92,957). Depression was heritable in participants reporting trauma exposure and in unexposed individuals, and the genetic correlation between the groups was substantial and not significantly different from 1. Genetic correlations between depression and psychiatric traits were strong regardless of reported trauma exposure, whereas genetic correlations between depression and body mass index (and related phenotypes) were observed only in trauma exposed individuals. The narrower range of genetic correlations in trauma unexposed depression and the lack of correlation with BMI echoes earlier ideas of endogenous depression.

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A genome-wide association study finds novel genetic associations with broadly-defined headache in UK Biobank (N = 223,773)

10.1101/217786 ◽

2017 ◽

Author(s):

Weihua Meng ◽

Mark J Adams ◽

Harry L Hebert ◽

Ian J Deary ◽

Andrew M McIntosh ◽

...

Keyword(s):

Association Study ◽

Genome Wide Association Study ◽

Genetic Correlations ◽

Genome Wide Association ◽

Uk Biobank ◽

Genetic Associations ◽

Psychological Traits ◽

Genome Wide ◽

A Genome ◽

The Uk

AbstractHeadache is the most common neurological symptom and a leading cause of years lived with disability. We sought to identify the genetic variants associated with a broadly-defined headache phenotype in 223,773 subjects from the UK Biobank cohort. We defined headache based on a specific question answered by the UK Biobank participants. We performed a genome-wide association study of headache as a single entity, using 74,461 cases and 149,312 controls. We identified 3,343 SNPs which reached the genome-wide significance level of P < 5 × 10−8. The SNPs were located in 28 loci, with the top SNP of rs11172113 in the LRP1 gene having a P value of 4.92 × 10−47. Of the 28 loci, 14 have previously been associated with migraine. Among 14 new loci, rs77804065 with a P value of 5.87 × 10−15 in the LINC02210-CRHR1 gene was the top SNP.Positive relationships (P < 0.001) between multiple brain tissues and genetic associations were identified through tissue expression analysis, whereas no vascular related tissues showed significant relationships. We identified several significant positive genetic correlations between headache and other psychological traits including neuroticism, depressive symptoms, insomnia, and major depressive disorder.Our results suggest that brain function is closely related to broadly-defined headache. In addition, we also found that many psychological traits have genetic correlations with headache.

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Insights into the aetiology of snoring from observational and genetic investigations in the UK Biobank (n=408,317)

10.1101/808691 ◽

2019 ◽

Author(s):

Adrián I. Campos ◽

Luis M. García-Marín ◽

Enda M. Byrne ◽

Nicholas G. Martin ◽

Gabriel Cuéllar-Partida ◽

...

Keyword(s):

Genetic Correlations ◽

Whole Body ◽

Mendelian Randomisation ◽

Uk Biobank ◽

Genome Wide ◽

A Genome ◽

Obstructive Sleep ◽

Polygenic Scores ◽

The Uk ◽

Cardinal Symptom

ABSTRACTWe conducted the largest study of snoring using data from the UK Biobank (n ∼ 408,000; snorers ∼152,000). A genome-wide association study (GWAS) identified 42 genome-wide significant loci, with a SNP-based heritability estimate of ∼10% on the liability scale. Genetic correlations with body mass index, alcohol intake, smoking, schizophrenia, anorexia nervosa and neuroticism were observed. Gene-based associations identified 173 genes, including DLEU7, MSRB3 and POC5 highlighting genes expressed in brain, cerebellum, lungs, blood, and oesophagus tissues. We used polygenic scores (PGS) to predict recent snoring and probable obstructive sleep apnoea (OSA) in an independent Australian sample (n∼8,000). Mendelian randomisation analyses provided evidence that larger whole body fat mass causes snoring. Altogether, our results uncover new insights into the aetiology of snoring as a complex sleep-related trait and its role in health and disease beyond being a cardinal symptom of OSA.

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Shared genetic aetiology between cognitive functions and physical and mental health in UK Biobank (N = 112 151) and 24 GWAS consortia.

10.1101/031120 ◽

2015 ◽

Cited By ~ 2

Author(s):

Saskia P Hagenaars ◽

Sarah E Harris ◽

Gail Davies ◽

William David Hill ◽

David CM Liewald ◽

...

Keyword(s):

Physical Health ◽

Test Scores ◽

Genome Wide Association Study ◽

Genetic Correlations ◽

Cognitive Test ◽

Uk Biobank ◽

Genome Wide ◽

The Uk ◽

Mental And Physical Health ◽

Shared Genetic

The causes of the known associations between poorer cognitive function and many adverse neuropsychiatric outcomes, poorer physical health, and earlier death remain unknown. We used linkage disequilibrium regression and polygenic profile scoring to test for shared genetic aetiology between cognitive functions and neuropsychiatric disorders and physical health. Using information provided by many published genome-wide association study consortia, we created polygenic profile scores for 24 vascular-metabolic, neuropsychiatric, physiological-anthropometric, and cognitive traits in the participants of UK Biobank, a very large population-based sample (N = 112 151). Pleiotropy between cognitive and health traits was quantified by deriving genetic correlations using summary genome-wide association study statistics applied to the method of linkage disequilibrium regression. Substantial and significant genetic correlations were observed between cognitive test scores in the UK Biobank sample and many of the mental and physical health-related traits and disorders assessed here. In addition, highly significant associations were observed between the cognitive test scores in the UK Biobank sample and many polygenic profile scores, including coronary artery disease, stroke, Alzheimer's disease, schizophrenia, autism, major depressive disorder, BMI, intracranial volume, infant head circumference, and childhood cognitive ability. Where disease diagnosis was available for UK Biobank participants we were able to show that these results were not confounded by those who had the relevant disease. These findings indicate that a substantial level of pleiotropy exists between cognitive abilities and many human mental and physical health disorders and traits and that it can be used to predict phenotypic variance across samples.

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Heritability And Genetic Correlations For Hormone-Sensitive Cancers In The UK Biobank: A Molecular Evidence of Shared Aetiology

10.21203/rs.3.rs-926833/v1 ◽

2021 ◽

Author(s):

Muktar Ahmed ◽

Ville-Petteri Mäkinen ◽

Anwar Mulugeta ◽

Jisu Shin ◽

Terry Boyle ◽

...

Keyword(s):

Genome Wide Association Study ◽

Genetic Correlations ◽

Significant Proportion ◽

Molecular Evidence ◽

Nucleotide Polymorphisms ◽

Uk Biobank ◽

Genome Wide ◽

A Genome ◽

Hormone Sensitive ◽

The Uk

Abstract Hormone-related cancers, including cancers of the breast, prostate, ovaries, uterine, and thyroid, globally contribute to the majority of cancer incidence. We hypothesize that hormone-sensitive cancers share common genetic risk factors that have rarely been investigated by previous genomic studies of site-specific cancers. To test this hypothesis, we analysed five hormone-sensitive cancers in the UK Biobank as a single disease. We observed that a significant proportion of variance in disease liability was explained by the genome-wide single nucleotide polymorphisms (SNPs), i.e., SNP-based heritability on the liability scale was estimated as 10.06% (SE 0.70%) for the disease. Moreover, we found 55 genome-wide significant SNPs for the disease, using a genome-wide association study. Our finding suggests that heritable genetic factors may be a key driver in the mechanism of carcinogenesis shared by hormone-sensitive cancers.

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The genetic and environmental hierarchical structure of anxiety and depression in the UK Biobank

10.31234/osf.io/pzh9n ◽

2019 ◽

Author(s):

Geneviève Morneau-Vaillancourt ◽

Jonathan Richard Iain Coleman ◽

Kirstin Lee Purves ◽

Rosa Cheesman ◽

Christopher Rayner ◽

...

Keyword(s):

Social Isolation ◽

Depressive Disorders ◽

Current Knowledge ◽

Genetic Correlations ◽

Anxiety And Depression ◽

Generalized Anxiety ◽

Uk Biobank ◽

Genome Wide ◽

The Uk ◽

Mental Health Questionnaire

Background. Anxiety and depressive disorders can be classified under a bi-dimensional model, where depression and generalized anxiety disorder are represented by distress and the other anxiety disorders, by fear. The phenotypic structure of this model has been validated, but twin studies only show partial evidence for genetic and environmental distinctions between distress and fear. Moreover, the effects of genetic variants are mostly shared between anxiety and depression, but the genome-wide genetic distinction between distress and fear remain unexplored. This study aimed to examine the degree of common genetic variation overlap between distress and fear, and their associations with the psychosocial risk factors of loneliness and social isolation. Methods. We used genome-wide data from 157,366 individuals in the UK Biobank who answered a mental health questionnaire. Results. Genetic correlations indicated that depression and generalized anxiety had a substantial genetic overlap, and that they were genetically partially distinct from fear disorders. Associations with loneliness, but not social isolation, showed that loneliness was more strongly associated with both distress disorders than with fear. Conclusions. Our findings shed light on genetic and environmental mechanisms that are common and unique to distress and fear and contribute to current knowledge on individuals’ susceptibility to anxiety and depression.

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Genome-wide analyses of behavioural traits biased by misreports and longitudinal changes

10.1101/2020.06.15.20131284 ◽

2020 ◽

Cited By ~ 2

Author(s):

Angli Xue ◽

Longda Jiang ◽

Zhihong Zhu ◽

Naomi R. Wray ◽

Peter M. Visscher ◽

...

Keyword(s):

Association Studies ◽

Genetic Correlations ◽

Genome Wide Association Studies ◽

Uk Biobank ◽

Longitudinal Changes ◽

Genome Wide ◽

The Uk ◽

Almost All ◽

Cardiovascular Traits

AbstractGenome-wide association studies (GWAS) have discovered numerous genetic variants associated with human behavioural traits. However, behavioural traits are subject to misreports and longitudinal changes (MLC) which can cause biases in GWAS and follow-up analyses. Here, we demonstrate that individuals with higher disease burden in the UK Biobank (n = 455,607) are more likely to misreport or reduce their alcohol consumption (AC) levels, and propose a correction procedure to mitigate the MLC-induced biases. The AC GWAS signals removed by the MLC corrections are enriched in metabolic/cardiovascular traits. Almost all the previously reported negative estimates of genetic correlations between AC and common diseases become positive/non-significant after the MLC corrections. We also observe MLC biases for smoking and physical activities in the UK Biobank. Our findings provide a plausible explanation of the controversy about the effects of AC on health outcomes and a caution for future analyses of self-reported behavioural traits in biobank data.

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