Karin Verweij

Karin Verweij
Queensland Institute of Medical Research | QIMR · Genetic Epidemiology Laboratory

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164
Publications
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Publications

Publications (164)
Article
Background Mental health and cognitive achievement are partly heritable, highly polygenic, and associated with brain variations in structure and function. However, the underlying neural mechanisms remains unclear. Methods We investigated the association between genetic predispositions to various mental health and cognitive traits and a large set o...
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This study aims to disentangle the contribution of genetic liability, educational attainment (EA), and their overlap and interaction in lifetime smoking. We conducted genome-wide association studies (GWASs) in UK Biobank (N = 394,718) to (i) capture variants for lifetime smoking, (ii) variants for EA, and (iii) variants that contribute to lifetime...
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Background: For centuries, it has been suspected that the vulnerability to psychiatric problems might be heritable. In the 20th century, this was confirmed through twin and family studies, with heritability estimates ranging from ~30-40% for posttraumatic stress disorder and major depression to ~80 for schizophrenia and autism. In the 21st century...
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Individuals with schizophrenia have a reduced life-expectancy compared to the general population, largely due to an increased risk of cardiovascular disease (CVD). Clinical and epidemiological studies have been unable to unravel the nature of this relationship. We obtained summary-data of genome-wide-association studies of schizophrenia (N = 130 64...
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Many adolescents start using tobacco, alcohol, and cannabis. Genetic vulnerability, parent characteristics in young adolescence, and interaction (GxE) and correlation (rGE) between these factors could contribute to the development of substance use. Using prospective data from the TRacking Adolescent Individuals’ Lives Survey (TRAILS; N = 1,645), we...
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Human same-sex sexual behaviour (SSB) is heritable, confers no immediately obvious direct reproductive or survival benefit and can divert mating effort from reproductive opportunities. This presents a Darwinian paradox: why has SSB been maintained despite apparent selection against it? We show that genetic effects associated with SSB may, in indivi...
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Epidemiological studies show high comorbidity between different mental health problems, indicating that individuals with a diagnosis of one disorder are more likely to develop other mental health problems. Genetic studies reveal substantial sharing of genetic factors across mental health traits. However, mental health is also genetically correlated...
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Behaviors and disorders related to self-regulation, such as substance use, antisocial behavior and attention-deficit/hyperactivity disorder, are collectively referred to as externalizing and have shared genetic liability. We applied a multivariate approach that leverages genetic correlations among externalizing traits for genome-wide association an...
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Background Structural variation in subcortical brain regions has been linked to substance use, including the most commonly used substances nicotine and alcohol. Pre-existing differences in subcortical brain volume may affect smoking and alcohol use, but there is also evidence that smoking and alcohol use can lead to structural changes. Aims We ass...
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Background Patients with psychiatric disorders often experience cognitive dysfunction, but the precise relationship between cognitive deficits and psychopathology remains unclear. We investigated the relationships between domains of cognitive functioning and psychopathology in a transdiagnostic sample using a data-driven approach. Methods Cross-se...
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Background Poor mental health has consistently been associated with substance use (smoking, alcohol drinking, cannabis use, and consumption of caffeinated drinks). To properly inform public health policy it is crucial to understand the mechanisms underlying these associations, and most importantly, whether or not they are causal. Methods In this p...
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Genome-wide association studies on human behavioural traits are producing large amounts of polygenic signals with significant predictive power and potentially useful biological clues. Behavioural traits are more distal and are less directly under biological control compared with physical characteristics, which makes the associated genetic effects h...
Preprint
This phenomewide association study examined SNP and genebased associations of the CADM2 gene with 242 psychobehavioral traits (N=12,211 to 453,349). We found significant associations with 51 traits, many more than for other genes. We replicated previously reported associations with substance use, risk taking, and health behavior, and uncovered nove...
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Hamer et al . argue that the variable “ever versus never had a same-sex partner” does not capture the complexity of human sexuality. We agree and said so in our paper. But Hamer et al . neglect to mention that we also reported follow-up analyses showing substantial overlap of the genetic influences on our main variable and on more nuanced measures...
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Background Cognitive dysfunction is widespread in psychiatric disorders and can significantly impact quality of life. Deficits cut across traditional diagnostic boundaries, necessitating new approaches to understand how cognitive function relates to large-scale brain activity and psychiatric symptoms across the diagnostic spectrum. Objective Using...
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Gene-environment correlations can bias associations between genetic variants and complex traits in genome-wide association studies (GWASs). Here, we control for geographic sources of gene-environment correlation in GWASs on 56 complex traits (N=69,772-271,457). Controlling for geographic region significantly decreases heritability signals for SES-r...
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Mental health and cognitive achievement are partly heritable. To identify the underlying neural mechanisms, we associated genetic predispositions to various mental health and cognitive traits with a large set of structural and functional brain measures from the UK Biobank (N=36,799). We show that genetic predispositions to attention deficit hyperac...
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Risky behaviors, such as substance use and unprotected sex, are associated with various physical and mental health problems. Recent genome-wide association studies indicated that variation in the cell adhesion molecule 2 (CADM2) gene plays a role in risky behaviors and self-control. In this phenome-wide scan for risky behavior, it was tested if und...
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The heart muscle diseases hypertrophic (HCM) and dilated (DCM) cardiomyopathies are leading causes of sudden death and heart failure in young, otherwise healthy, individuals. We conducted genome-wide association studies and multi-trait analyses in HCM (1,733 cases), DCM (5,521 cases) and nine left ventricular (LV) traits (19,260 UK Biobank particip...
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Background A recent study investigated the genetic associations and latent genetic structure among eight psychiatric disorders using findings from genome-wide association studies (GWASs). No data from substance use disorders were included, while these represent an important category of mental disorders and could influence the latent genetic structu...
Preprint
Full-text available
Behaviors and disorders related to self-regulation, such as substance use, antisocial conduct, and ADHD, are collectively referred to as externalizing and have a shared genetic liability. We applied a multivariate approach that leverages genetic correlations among externalizing traits for genome-wide association analyses. By pooling data from ~1.5...
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Full-text available
Background Poor sleep quality and insomnia have been associated with the use of tobacco, alcohol, and cannabis, but it is unclear if there is a causal link. In this Mendelian Randomization (MR) study we examine if insomnia causes substance use and/or if substance use causes insomnia. Methods MR uses summary effect estimates from a genome-wide asso...
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Family studies have identified a heritable component to self-harm that is partially independent from comorbid psychiatric disorders. However, the genetic aetiology of broad sense (non-suicidal and suicidal) self-harm has not been characterised on the molecular level. In addition, controversy exists about the degree to which suicidal and non-suicida...
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Background and aims: A recent study investigated the genetic associations and latent genetic structure among eight psychiatric disorders using findings from genome-wide association studies (GWASs). No data from substance use disorders were included, while these represent an important category of mental disorders and could influence the latent genet...
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Genetic research into human sexuality was scarce at the end of last century. In 1992 Nick developed a 12-page questionnaire to send to twins to investigate the underpinnings of sexuality. The questionnaire included items about sexual orientation, sociosexuality and sexual behavior, and was completed by almost 5000 twins. The resulting data, unique...
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Background The use of illicit substances is correlated, meaning that individuals who use one illicit substance are more likely to also use another illicit substance. This association could (partly) be explained by overlapping genetic factors. Genetic overlap may indicate a common underlying genetic predisposition, or can be the result of a causal a...
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Background: Patients with psychiatric disorders, such as major depressive disorder, schizophrenia or obsessive-compulsive disorder, often suffer from cognitive dysfunction. The nature of these dysfunctions and their relation with clinical symptoms and biological parameters is not yet clear. Traditionally, cognitive dysfunction is studied in patien...
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Background and Aims Loneliness is associated with cigarette smoking and problematic alcohol use. Observational evidence suggests these associations arise because loneliness increases substance use; however, there is potential for reverse causation (problematic drinking damages social networks, leading to loneliness). With conventional epidemiologic...
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Background: Poor sleep quality and insomnia have been associated with the use of tobacco, alcohol, and cannabis, but it is unclear if there is a causal link. In this Mendelian Randomization (MR) study we examine if insomnia causes substance use and/or if substance use causes insomnia. Methods: MR uses summary effect estimates from a genome-wide ass...
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Background Caffeine, alcohol, nicotine and cannabis are commonly used psychoactive substances. While the use of these substances has been previously shown to be genetically correlated, causality between these substance use traits remains unclear. We aimed to revisit the genetic relationships among different measures of SU using genome-wide associat...
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Objective Ecstasy is one of the most commonly used illicit substances in Western countries. The aim of this study is to identify characteristics of ecstasy users in a large population-based sample of adults aged 18-45 years. Method With generalized estimating equation models we explored the association between self-reported lifetime ecstasy use an...
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Full-text available
Epidemiological studies show high comorbidity between different mental health problems, indicating that individuals with a diagnosis of one disorder are more likely to develop other mental health problems. Genetic studies reveal substantial sharing of genetic risk factors across mental health traits. However, mental health is genetically correlated...
Article
The ratio of males to females among an individual's offspring at birth (offspring sex ratio) has long been of great interest to evolutionary biologists. The human offspring sex ratio is around 1 : 1 and is understood primarily in terms of Fisher's principle (R. A. Fisher, The genetical theory of natural selection, 1930), which is based on the insig...
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Background Tobacco, alcohol, and cannabis use are prevalent behaviors that pose considerable health risks. Genetic vulnerability and characteristics of the neighborhood of residence form important risk factors for substance use. Possibly, these factors do not act in isolation. This study tested the interaction between neighborhood characteristics a...
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Human DNA polymorphisms vary across geographic regions, with the most commonly observed variation reflecting distant ancestry differences. Here we investigate the geographic clustering of common genetic variants that influence complex traits in a sample of ~450,000 individuals from Great Britain. Of 33 traits analysed, 21 showed significant geograp...
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We investigated whether obsessive–compulsive (OC) symptoms from a population‐based sample could be analyzed to detect genetic variants influencing obsessive–compulsive disorder (OCD). We performed a genome‐wide association studies (GWAS) on the obsession (rumination and impulsions) and compulsion (checking, washing, and ordering/precision) subscale...
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Attention-deficit hyperactivity disorder (ADHD) has consistently been associated with substance use, but the nature of this association is not fully understood. To inform intervention development and public health messages, a vital question is whether there are causal pathways from ADHD to substance use and/or vice versa. We applied bidirectional M...
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Using data from 5500 adolescents from the National Longitudinal Study of Adolescent to Adult Health, Domingue et al. (Proc Natl Acad Sci 25:256., 2018) claimed to show that friends are genetically more similar to one another than randomly selected peers, beyond the confounding effects of population stratification by ancestry. The authors also claim...
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Background: Little is known about the functional mechanisms through which genetic loci associated with substance use traits ascertain their effect. This study aims to identify and functionally annotate loci associated with substance use traits based on their role in genetic regulation of gene expression. Methods: We evaluated expression Quantita...
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Humans are social animals that experience intense suffering when they perceive a lack of social connection. Modern societies are experiencing an epidemic of loneliness. While the experience of loneliness is universally human, some people report experiencing greater loneliness than others. Loneliness is more strongly associated with mortality than o...
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Twin and family studies have shown that same-sex sexual behavior is partly genetically influenced, but previous searches for specific genes involved have been underpowered. We performed a genome-wide association study (GWAS) on 477,522 individuals, revealing five loci significantly associated with same-sex sexual behavior. In aggregate, all tested...
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Studies testing the effect of single genetic variants on substance use have had modest success. This paper reviewed 39 studies using polygenic measures to test interaction with any type of environmental exposure (G×E) in alcohol, tobacco, and cannabis use. Studies using haplotype combinations, sum scores of candidate-gene risk alleles, and polygeni...
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Several occurrences of the word ‘schizophrenia’ have been re-worded as ‘liability to schizophrenia’ or ‘schizophrenia risk’, including in the title, which should have been “GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability,” as well as in Supplementary Figure...
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A commentary on Di Forti et al., 2019: 'The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study.'
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Full-text available
Using data from 5,500 adolescents from the National Longitudinal Study of Adolescent to Adult Health, Domingue et al. (2018) claimed to show that friends are genetically more similar to one another than randomly selected peers, beyond the confounding effects of population stratification by ancestry. The authors also claimed to show "social-genetic"...
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Full-text available
Not much is known regarding underlying biological pathways to adolescents’ loneliness. Insight in underlying molecular mechanisms could inform intervention efforts aimed at reducing loneliness. Using latent growth curve modeling, baseline levels and development of loneliness were studied in two longitudinal adolescent samples. Genes (OXTR, OXT, AVP...
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Background Recent large-scale Genome-Wide Association Studies (GWAS) have identified genetic loci associated with various substance use traits. However, little is known about the functional mechanisms through which these genetic loci ascertain their effect. This study aims to identify and functionally annotate genetic loci associated with substance...
Preprint
Full-text available
A bstract Humans are social animals that experience intense suffering when they perceive a lack of social connection. Modern societies are experiencing an epidemic of loneliness. While the experience of loneliness is universally human, some people report experiencing greater loneliness than others. Loneliness is more strongly associated with mortal...
Preprint
Full-text available
Human DNA varies across geographic regions, with most variation observed so far reflecting distant ancestry differences. Here, we investigate the geographic clustering of genetic variants that influence complex traits and disease risk in a sample of ~450,000 individuals from Great Britain. Out of 30 traits analyzed, 16 show significant geographic c...
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Full-text available
Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study (GWAS) for lifetime cannabis use to date (N = 184,765), we identified eight genome-wide significant independent single nucleotide polymorphisms in six regions. All measured genetic variants combined explained...
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Introduction: Cigarette smoking and cannabis use are heritable traits and share, at least in part, a common genetic substrate. In recent years the prevalence of alternative methods of nicotine intakes, such as e-cigarette and water pipe use, has risen substantially. We tested whether the genetic vulnerability underlying cigarettes smoking and canna...
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Background and aims Cannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes including multi‐substance use and dependence. This study estimated the heritability of age at first cannabis use and identify associations with genetic variants. Methods...
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Objective: Loneliness is an aversive response to a discrepancy between desired and actual social relationships and correlates with personality. We investigate the relationship of loneliness and personality in twin‐family and molecular genetic data. Method: Phenotypic correlations between loneliness and the Big Five personality traits were estimated...
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Background Body mass index (BMI) is correlated negatively with subjective well-being and positively with depressive symptoms. Whether these associations reflect causal effects is unclear. Methods We examined bidirectional, causal effects between BMI and mental health with Mendelian randomisation using summary-level data from published genome-wide...
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Background: There is high comorbidity between antisocial behaviour (ASB) and substance use, and twin studies have shown that part of the covariation is due to overlapping genetic influences. Here we used measured genetic effects to estimate the genetic correlations of ASB with nicotine, alcohol, and cannabis use. Methods: We meta-analysed data f...