Jan Sundquist

• Lund University

We seek to clarify the impact of the Genetic Aptitude for Educational Attainment (GAEA) on risk for 10 psychiatric disorders divided into 4 groups: Internalizing, Externalizing, Eating/Compulsive and Psychotic. Educational attainment and psychiatric and substance use disorder information were obtained from national Swedish registries. GAEA and diso...

Familial clustering of lung cancer (LC) is related to shared smoking habits but the contribution of other potential factors such as sex or histology is not well known, and these are the subjects of the present study in Sweden. Family relationships (from Multigeneration register) and diagnosed cancers (from Cancer registry) were obtained from the na...

Background We utilize a novel contrastive genetic-epidemiological method, the Maternal Half-Sibling Families with Discordant Fathers (MHSFDF) design, to examine cross-generational genetic transmission of posttraumatic stress disorder (PTSD) and related internalizing major depression (MD), and externalizing disorders: alcohol use disorder (AUD) and...

Background Stressful life events (SLEs) increase the risk for subsequent major depression (MD) episodes. Most prior studies of SLEs utilized questionnaires or interview-based assessments. We sought to develop and evaluate an environmental risk score (ERS) for MD from multiple classes of SLEs obtained from national Swedish registries. Methods We as...

Background We seek to clarify how changes in the prevalence of drug use disorder (DUD) in Sweden in the 1950–1990 birth cohort impact the aggregation and co-aggregation in siblings of DUD and alcohol use disorder (AUD). Methods We examined risk for DUD and AUD in siblings of 102,624 DUD cases and matched control probands and 123,837 AUD case and m...

Objective To explore temporal changes in incidence of major psychiatric disorders across sociodemographic subgroups in Sweden. Methods This population-based open cohort study included all individuals born during 1958–1994 and residing in Sweden at any time during 2004–2019. We identified psychiatric disorders registered in inpatient and outpatient...

Background Psychiatric disorders have been associated with venous thromboembolism (VTE). However, to our knowledge, no nationwide study has examined the familial association between VTE and psychiatric disorders. Objectives We took a pedigree-based approach and examined the risk of psychiatric disorders in offspring from extended pedigrees accordi...

In addition to biological factors, maternal exposures during pregnancy can contribute to leukemogenesis in offspring. We conducted a population-based cohort study in Sweden to investigate the association between risk of acute lymphoblastic leukemia (ALL) in offspring and maternal anthropometrics during pregnancy. A total of 2,961,435 live-born sing...

We aimed to investigate the school performance gap and its potential trend from 2010 to 2020 in non-immigrant and second-generation immigrant children in Sweden, whether parental mental disorders and low socioeconomic status contribute to this gap and its trends, and whether the effects of these factors differ by immigration status. We used multipl...

Venous thromboembolism (VTE) involves blood clot formation in veins, resulting in serious health issues. Fibrinogen, a crucial clotting protein, consists of three polypeptides encoded by the fibrinogen genes: alpha (FGA), beta (FGB) and gamma (FGG). We genotyped most common missense variants in the fibrinogen genes in relation to VTE, recurrence an...

While extensive research exists on the severe consequences among rape victims, little is known about specific predictors in relation to rape convictions among immigrants to Europe. This study from Sweden (having one of Europe’s highest per capita rates of rape) investigates individuals convicted of rape, aggravated rape, attempted rape, or attempte...

Objective: Information on how parental risk for posttraumatic stress disorder (PTSD) relates to their children’s risk for drug use disorder (DUD) and alcohol use disorder (AUD) is limited. This study is the first to utilize an extended adoption design which can address questions about the degree of, and sources of, cross-generational and cross-diso...

Background Drug use Disorder (DUD), the risk for which is substantially influenced by both genetic and social factors, is geographically concentrated in high-risk regions. An important step toward understanding this pattern is to examine geographical distributions of the genetic liability to DUD and a key demographic risk factor – social deprivatio...

Background Robust clinical indices of etiologic heterogeneity for psychiatric disorders are rare. We investigate whether age at onset (AAO) reflects genetic heterogeneity, utilizing Genetic Risk Ratios (GRR) derived from Family Genetic Risk Scores (FGRS). Methods We examined, in individuals born in Sweden 1940–2003, whether AAO for five primary di...

Background and aims: Environmental and genetic factors predispose to cardiovascular disease. Some first-generation immigrants have a higher cardiovascular risk in Sweden, while less is known about second-generation immigrants. We aimed to analyze the risk of acute myocardial infarction (AMI) among second-generation immigrants in Sweden. Methods: W...

Background: Parents experience a range of mental health disorders following their child’s cancer diagnosis. It is thus essential to explore how the child’s cancer diagnosis affects the dosage of psychotropic medication in both short- and long-term use, as well as potential disparities in utilization patterns between mothers and fathers. Patients an...

Background Little is known about whether the protective effect of marriage on alcohol use disorder (AUD) varies by cultural background. Aims Using Swedish national data, we examined whether marriage is associated with a stronger reduction in AUD risk among Swedes of a Swedish background (i.e. those with two Swedish-born parents) compared to Swedes...

Background Accumulating studies reported that several phosphodiesterases (PDEs) inhibitors might have cardiovascular benefits. Objectives This study aimed to explore the relationship between genetically-predicted PDEs and ischemia heart disease via drug target Mendelian randomization (MR) approach, and then examine the effect of inhibitors of iden...

Introduction Thyroid cancer (TC) is diagnosed in several histological types which differ in their clinical characteristics and survival. We aim to describe how they influence TC survival in Sweden. Methods Cancer data were obtained from the Swedish cancer registry between years 1999 and 2018, and these were used to analyze relative survival. Resu...

Background Suicidal behaviors are prevalent public health concerns, and we need to improve our predictive ability to better inform prevention efforts. Methods Using nationwide longitudinal Swedish registers, we included 344,490 males and 323,177 females born 1982–1990 with information on genetic liability and environmental exposures from birth to...

Background Men with prostate cancer (PC) may experience significant psychosocial distress from physical symptoms, treatment side effects, or fear of recurrence. However, little is known about the long-term risk of anxiety disorders in men with PC. Methods A national cohort study was conducted of 180,189 men diagnosed with PC during 1998-2017 and 1...

Sweden has an immigrant-native wage gap. Although the impact of educational attainment and other variables have been studied, the impact of specific personality traits analyzed separately on the wage gap remains poorly understood. In this study, we used a unique dataset that usually contains unobserved personality traits evaluated by psychologists...

We investigate whether number of episodes (NoEs) meaningfully reflect genetic risk and genetic heterogeneity for five primary disorders—Drug Use Disorder (DUD), Alcohol Use Disorder (AUD), Major Depression (MD), Bipolar Disorder (BD), and Schizophrenia (SZ) ascertained from Swedish population registries. We utilize Genetic Risk Ratios (GRR)—defined...

Background There is increasing evidence implicating hemoglobin/heme and their scavengers in oxidative stress-mediated pathologies, but information is limited in abdominal aortic aneurysm (AAA). Methods and results In this case-control study, we assessed heme/heme-related markers in 142 men with AAA and 279 men with a normal aortic diameter consecu...

Maternal exposures during pregnancy are critical for leukemogenesis in offspring since childhood leukemia often originates in utero. We conducted a population-based cohort study in Sweden to investigate the association between the risk of acute lymphoblastic leukemia (ALL) in offspring and maternal anthropometrics during pregnancy, including gestat...

Purpose: We aimed to analyze the risk of hereditary hemochromatosis (HH) among first-generation and second-generation immigrants in Sweden using Swedish-born individuals and Swedish-born individuals with Swedish-born parents as referents, respectively. Methods: All individuals aged 18 years of age and older, n = 6,180,500 in the first-generation st...

Objective: There is growing interest in how peers' genotypes may influence health (i.e., peer social genetic effects). The authors sought to clarify the nature of peer social genetic effects on risk for drug use disorder, alcohol use disorder (AUD), major depression, and anxiety disorder. Method: Cox models were used with data from a population-...

Purpose We aimed at analysing the risk of congestive heart failure (CHF) among first‐ and second‐generation immigrants in younger age groups. Methods All individuals aged 18–54 years, n = 3 973 454 in the first‐generation study and n = 3 817 560 in the second‐generation study, were included. CHF was defined as at least one registered diagnosis in...

Background and Hypothesis To clarify, in a large, representative, longitudinal sample, the rate and predictors of diagnostic conversion from Bipolar Disorder (BD) to Schizophrenia (SZ) and from SZ→BD. Design From individuals born in Sweden 1950–1995 and living there in 1970 or later, we identified at least one initial diagnoses of SZ (n = 8449) an...

The human sex ratio at birth (SRB) undergoes temporary changes around a mean proportion of 0.51 male births. SRB has been well studied for historical, geographical, and secular trends, but until now not linked to health outcomes in the total population, e.g. for cardiovascular disease (CVD) or mortality during follow-up of birth cohorts. We used li...

Using a case-controlled study including siblings of major depression (MD) and control probands, born 1970–1990 and followed through 2018, we sought to clarify the degree to which the familial liability to MD is reflected in its clinical features, and the pattern of psychiatric disorders at elevated risk in the siblings of MD probands. The study pop...

Background Mitochondrial DNA copy number (mtDNA-CN) is associated with aging. A relationship between mtDNA-CN and degenerative disorders, e.g. osteoarthritis (OA) and osteoporosis (OP), has been suggested. We aimed to investigate the relationship of mtDNA-CN and incident OA and OP. Materials and methods MtDNA-CN was studied in relationship to inci...

To examine whether the level of genetic risk in psychiatric disorders impacts the social functioning of affected individuals, we examine the relationship between genetic risk factors for major depression (MD), anxiety disorders (AD), bipolar disorder (BD), non‐affective psychosis (NAP), alcohol use disorder (AUD), and drug use disorder (DUD) in dis...

Importance Twin studies have found that posttraumatic stress disorder (PTSD) is influenced by both genetic and environmental factors within a generation. No study has used an adoption design, which can address questions about the degree and sources of cross-generational transmission of adverse stress responses (ASRs) and PTSD. Objectives To examin...

Objective: Twin studies have demonstrated that posttraumatic stress disorder (PTSD) is moderately heritable, and the pattern of findings across studies suggests higher heritability in females compared with males. Formal testing of sex differences has yet to be done in twin studies of PTSD. The authors sought to estimate the genetic and environment...

We studied the risk of acute myocardial infarction in both first- and second-generation immigrants in Sweden, i.e. foreign-born individuals in relation to Swedish-born individuals. • The risk of acute myocardial infarction was similar in foreign-born men, but lower in foreign-born women and women with foreign-born parents, in relation to native Sw...

Hereditary angioedema (HAE) due to C1 inhibitor protein (C1-INH) deficiency was recently shown to be associated with increased risk of venous thromboembolism (VTE). This is the first national family study of HAE with the aim to determine the familial risk of VTE. The Swedish Multi-Generation Register was linked to the Swedish National Patient Regis...

OBJECTIVE To examine long-term diabetes risk after preterm delivery or hypertensive disorders of pregnancy in a large population-based cohort. METHODS This retrospective cohort study included all women with a singleton delivery in Sweden during 1973–2015 and no preexisting diabetes mellitus. Participants were followed up for development of type 2...

Importance For individuals without a family history of colorectal cancer (CRC), colonoscopy screening every 10 years is recommended to reduce CRC incidence and mortality. However, debate exists about whether and for how long this 10-year interval could be safely expanded. Objective To assess how many years after a first colonoscopy with findings n...

Multimorbidity, i.e., two or more non-communicable diseases (NCDs), is an escalating challenge for society. Venous thromboembolism (VTE) is a common cardiovascular disease and it is unknown which multimorbidity clusters associates with VTE. Our aim was to examine the association between different common disease clusters of multimorbidity and VTE. T...

Importance Women with adverse pregnancy outcomes, such as preterm delivery or preeclampsia, have higher future risks of cardiometabolic disorders; however, little is known about their long-term mortality risks. A better understanding of such risks is needed to facilitate early identification of high-risk women and preventive actions. Objective To...

INTRODUCTION Depression is a risk factor and possible prodromal symptom of Alzheimer's disease (AD), but little is known about subsequent risk of developing depression in persons with AD. METHODS National matched cohort study was conducted of all 129,410 persons diagnosed with AD and 390,088 with all‐cause dementia during 1998–2017 in Sweden, and...

Background There is a lack of studies on sarcoidosis among immigrants, which is of interest as there may be genetic and environmental characteristics affecting immigrants from certain countries. We aimed to study hazard ratios (HRs) of sarcoidosis in first- and second-generation immigrants, comparing them with native Swedes in the total adult Swedi...

Introduction Alcohol use disorder (AUD) is among the strongest correlates of suicide death, but it is unclear whether AUD status is differentially associated with risk of suicide by particular methods. Methods The authors used competing risks models to evaluate the association between AUD status and risk of suicide by poisoning, suffocation, drown...

Introduction Resting heart rate has been distinctly related to both internalizing (high pulse) and externalizing (low pulse) disorders. We aimed to explore the associations between resting heart rate and suicidal behavior (nonfatal suicide attempt [SA] and suicide death [SD]) and evaluate if such associations exist beyond the effects of internalizi...

Backround We wanted to characterize conditional survival in prostate cancer (PC) in Sweden around and after 2005 when the vast increase in incidence due to the opportunistic testing for prostate specific antigen (PSA) culminated. We hypothesize that analyzing survival data during that time period may help interpret survival trends. We focus on stag...

Background Alcohol consumption contributes to excess morbidity and mortality in part through the development of alcohol-related medical conditions (AMCs, including alcoholic cardiomyopathy, hepatitis, cirrhosis, etc.). The current study aimed to clarify the extent to which risk for these outcomes differs as a function of socioeconomic position (SEP...

Human papillomavirus can be contracted by sexually active women. However, only a small proportion of these infections persist and have the potential to progress into cervical cancers, indicating a significant involvement of the immune system in cervical cancer development. Despite this, our understanding of the precise contributions of genes from d...

Objective: The authors sought to clarify the components of the familial liability to alcohol use disorder (AUD) by examining parent-offspring transmission in a large Swedish population sample. Methods: To this end, 1,244,516 offspring in intact families with a mean age at follow-up of 37.7 years (SD=6.8) were examined. Hazard ratios for offsprin...

Introduction The Interpersonal‐Psychological Theory of Suicide proposes that capability for suicide is acquired through exposure to painful and provocative events (PPEs). Although there is robust evidence for a positive association between aggregate measures of PPEs and risk for suicidal behavior, little is known about the contributions of physical...

Findings on the correlation between the use of antihypertensive medication and the risk of breast cancer (BC) have been inconsistent. We performed a two-sample Mendelian randomization (MR) using instrumental variables to proxy changes in gene expressions of antihypertensive medication targets to interrogate this. Genetic instruments for expression...

Despite recent progress in the genetics of suicidal behavior, the pathway by which genetic liability increases suicide attempt risk is unclear. We investigated the mediational pathways from family/genetic risk for suicide attempt (FGRS SA ) to suicide attempt by considering the roles of psychiatric illnesses. In a Swedish cohort, we evaluated time...

Background The concept of schizotypal personality disorder (SPD) emerged from observations of personality characteristics common in relatives of schizophrenic patients. While often studied in family designs, few studies and none with genetic measures, have examined SPD in epidemiological samples. Methods We studied individuals born in Sweden 1940–...

Background Little is known about risks of hypertensive disorders of pregnancy in both first‐ and second‐generation immigrant women in Europe and other Western countries; such knowledge may help elucidate the influence of genetic versus social factors on such risks. We aimed to study both first‐ and second‐generation immigrant women for the presence...

Background One potential cause of comorbidity is the direct causal effect of one disorder – A – on risk for subsequent onset of disorder B. Could genetic risk scores be utilized to test for such an effect? If disorder A causally impacts on risk for disorder B, then genetic risk for disorder A should be lower in cases of disorder A with v. without a...

We used Swedish national-register data ( N = 2,828,777) to examine divorce and its associated patterns of family genetic-risk scores (FGRSs; personalized measures of genetic risk inferred from diagnoses in relatives) across 10 psychiatric disorders: major depression, anxiety disorders, obsessive compulsive disorder, bipolar disorder, schizophrenia,...

• Objective: Consistent guidelines for colonoscopy screening intervals in population with a family history of colorectal cancer (CRC) are lacking. This study aims to provide evidence regarding the timing of a second colonoscopy screening in individuals with a family history of late-onset CRC. • Methods: We conducted a nationwide matched cohort stud...

Background To determine whether genetic risk factors for major depression (MD) and alcohol use disorder (AUD) interact with a potent stressor – death of spouse, parent, and sibling – in predicting episodes of, respectively, MD and AUD. MethodsMD and AUD registrations were assessed from national Swedish registries. In individuals born in Sweden 1960...

Using Swedish registers, we examine whether the prescription of and the response to antidepressants (AD), mood stabilizers (MS), and antipsychotics (AP) in the treatment of, respectively, major depression (MD), bipolar disorder (BD), and schizophrenia (SZ), are influenced by familial-genetic risk. We examined individuals born in Sweden 1960–1995 wi...

Background Prior research has reported an association between divorce and suicide attempt. We aimed to clarify this complex relationship, considering sex differences, temporal factors, and underlying etiologic pathways. Methods We used Swedish longitudinal national registry data for a cohort born 1960–1990 that was registered as married between 19...

Background A diagnosis of prostate cancer (PC) may cause psychosocial distress not only in a man but also his intimate partner. However, long-term risks of depression, anxiety, or suicide in partners of men with PC are largely unknown. Methods A national cohort study was conducted of 121,530 partners of men diagnosed with PC during 1998-2017 and 1...

Objectives Vasospastic angina (VSA) is a complex coronary vasomotor disorder associated with an increased risk of myocardial infarction and sudden death. Despite considerable advances in understanding VSA pathophysiology, the interplay between genetic and environmental factors remains elusive. Accordingly, we aimed to determine the familial VSA ris...

Background Drug repurposing provides a cost-effective approach to address the need for breast cancer prevention and therapeutics. We aimed to identify actionable druggable targets using Mendelian randomization (MR) and then validate the candidate drugs using population-based analyses. Methods We identified genetic instruments for 1406 actionable t...

Background: There are two primary phenotypic models of comorbidity between post-traumatic stress disorder (PTSD) and drug use disorder (DUD), i.e. self-medication (PTSD precedes and causes DUD) and susceptibility (DUD precedes and causes PTSD). We sought to clarify the longitudinal relationship between PTSD and DUD, while examining sex differences....

Background Breast cancer is, despite screening, not always detected early enough and is together with other tumor types known to shed genetic information in circulation. Unlike single-copy nuclear DNA, mitochondrial DNA (mtDNA) copies range from 100s to 10,000s per cell, thus providing a potentially alternative to identify potential missing cancer...

Background and aims: Alcohol use disorder (AUD) is one of the strongest predictors of suicidal behavior. Here, we measured risk of suicide attempt and death as a function of AUD typologies. Design: We used AUD typologies from previous latent class analysis: (i) externalizing subtype (characterized by externalizing symptomatology and early age of...

Aims: The aim of this study is to investigate how genetic variations in genes related to oxidative stress, intake of antioxidant vitamins, and any potential interactions between these factors affect the incidence of intact abdominal aortic aneurysm (AAA) and its rupture (rAAA), accounting for sex differences where possible. Methods and results:...

Objective: Drug use disorder (DUD) is a world-wide problem and strategies to reduce its incidence are central to decreasing its burden. This investigation seeks to provide a proof of concept for the ability of agent-based modeling to predict the impact of the introduction of an effective school-based intervention, the Good Behavior Game (GBG), on...

Mitochondrial dysfunction is a recognized factor in the pathogenesis of deep vein thrombosis (DVT). The role of 7S RNA, a long noncoding RNA that plays an important role in mitochondrial function, in DVT remains unclear. In this study, we aimed to investigate the potential use of 7S RNA as a biomarker in DVT. Plasma samples were obtained from 237 p...

Patients with bipolar disorder have higher rates of type 2 diabetes (T2D) compared to the general population. Neighbourhood deprivation is associated with T2D and bipolar disorder. The aim of this study was to explore the potential effect of neighbourhood deprivation on incident T2D in patients with bipolar disorder. This nationwide open cohort stu...

Purpose: To examine risks of attention-deficit/hyperactivity disorder (ADHD) in preterm and early term birth survivors, and potential sex-specific differences. Methods: A national cohort study was conducted of all 4,061,795 singletons born in Sweden in 1973-2013 who survived infancy, followed up for ADHD identified from nationwide diagnoses and...

Background Neighborhood deprivation has been found associated with both type 2 diabetes and lung cancer. The aim of this study was to examine the potential association between neighborhood deprivation and lung cancer incidence or mortality in individuals diagnosed with type 2 diabetes. The results may identify a new risk or prognostic factor for lu...

Objectives To examine whether multimorbidity aggregates in families in Sweden. Design National explorative family study. Setting Swedish Multigeneration Register linked to the National Patient Register, 1997-2015. Multimorbidity was assessed with a modified counting method of 45 chronic non-communicable diseases according to ICD-10 (international...

Background and hypothesis: To clarify whether the familial liability to psychosis associated with bipolar disorder (BD) is nonspecific or has a greater effect on risk for psychosis in cases with prominent mood symptoms and/or a remitting course. Study design: We examined, in 984 809 offspring raised in intact families in Sweden, born 1980-1996 a...

Background: Findings on the correlation between the use of antihypertensive medication and the risk of breast cancer (BC) have been inconsistent. We performed a two-sample Mendelian randomization (MR) using instrumental variables to proxy changes in gene expressions of antihypertensive medication targets to interrogate this. Methods: Genetic instru...

Background: It is clinically important to predict the conversion of major depression (MD) to bipolar disorder (BD). Therefore, we sought to identify related conversion rates and risk factors. Methods: This cohort study included the Swedish population born from 1941 onward. Data were collected from Swedish population-based registers. Potential ri...

We investigate how selection of psychiatric cases by phenotypic criteria can alter the strength and specificity of their genetic risk by examining samples from national Swedish registries for five disorders: major depression (MD, N = 158,557), drug use disorder (DUD, N = 69,841), bipolar disorder (BD, N = 13,530)) ADHD (N = 54,996) and schizophreni...

Background: Prostate cancer (PC) survivors may potentially use substances to cope with psychological distress or poorly-controlled physical symptoms. However, little is known about long-term risks of alcohol use disorder (AUD) or drug use disorders (DUD) in men with PC. Methods: A national cohort study was conducted in Sweden of 180,189 men diag...

Genetics as a science has roots in studying phenotypes of relatives, but molecular approaches facilitate direct measurements of genomic variation within individuals. Agricultural and human biomedical research are both emphasizing genotype-based instruments, like polygenic scores, as the future of breeding programs or precision medicine and genetic...

Fibromyalgia is a complex disease of unclear etiology that is complicated by difficulties in diagnosis, treatment, and clinical heterogeneity. To clarify this etiology, healthcare-based data are leveraged to assess the influences on fibromyalgia in several domains. Prevalence is less than 1% of females in our population register data, and about 1/1...