Samuel Edward Jones

• PhD Mathematics
• Research Associate at University of Helsinki

Article Genome-wide association study of long COVID Infections can lead to persistent symptoms and diseases such as shingles after varicella zoster or rheumatic fever after streptococcal infections. Similarly, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in long coronavirus disease (COVID), typically manifesting...

Article Genome-wide association study of long COVID Infections can lead to persistent symptoms and diseases such as shingles after varicella zoster or rheumatic fever after streptococcal infections. Similarly, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in long coronavirus disease (COVID), typically manifesting...

Introduction Sleep disorders affect over 30% of the population in the United States, making them among the most common yet underdiagnosed conditions with significant disease comorbidity and increase in mortality. Moreover, as occasional sleep problems are normal, clinical sleep disorders (CSDs) are often misinterpreted as normal variation in habitu...

Narcolepsy is a severe sleep disorder with characteristics of fatigue, fragmented sleep, cataplexy and hypnagogic hallucinations. Earlier clinical studies have reported the onset of schizophrenia after narcolepsy but the causality behind narcolepsy and schizophrenia is unknown. Our goal was to understand the causality between narcolepsy and schizop...

Puumala virus (PUUV) infections can cause severe illnesses such as Hemorrhagic Fever with Renal Syndrome in humans. However, human genetic risk factors contributing to disease severity are still poorly understood. Our goal was to elucidate genetic factors contributing to PUUV infections and understand the biological mechanisms underlying individual...

Disordered eating and self-harm commonly co-occur in young people suggesting potential for shared underlying causes. Body image dissatisfaction (BID) has been recognised as a psychological correlate of body size, associated with both disordered eating and self-harm. However, the investigation into etiological pathways early in the lifecourse to pro...

Raynaud’s syndrome is a dysautonomia where exposure to cold causes vasoconstriction and hypoxia, particularly in the extremities. We performed meta-analysis in four cohorts and discovered eight loci (ADRA2A, IRX1, NOS3, ACVR2A, TMEM51, PCDH10-DT, HLA, and RAB6C) where ADRA2A, ACVR2A, NOS3, TMEM51, and IRX1 co-localized with expression quantitative...

Circadian rhythms not only coordinate the timing of wake and sleep but also regulate homeostasis within the body, including glucose metabolism. However, the genetic variants that contribute to temporal control of glucose levels have not been previously examined. Using data from 420,000 individuals from the UK Biobank and replicating our findings in...

Self-reported shorter/longer sleep duration, insomnia, and evening preference are associated with hyperglycaemia in observational analyses, with similar observations in small studies using accelerometer-derived sleep traits. Mendelian randomization (MR) studies support an effect of self-reported insomnia, but not others, on glycated haemoglobin (Hb...

Lyme disease is a tick-borne disease caused by bacteria of the genus Borrelia. The host factors that modulate susceptibility for Lyme disease have remained mostly unknown. Using epidemiological and genetic data from FinnGen and Estonian Biobank, we identify two previously known variants and an unknown common missense variant at the gene encoding fo...

Background Congenital heart defects (CHD) are structural defects of the heart affecting approximately 1% of newborns. They exhibit low penetrance and non-Mendelian patterns of inheritance as varied and complex traits. While genetic factors are known to play an important role in the development of CHD, the specific genetics remain unknown for the ma...

Nightmares are vivid, extended, and emotionally negative or negative dreams that awaken the dreamer. While sporadic nightmares and bad dreams are common and generally harmless, frequent nightmares often reflect underlying pathologies of emotional regulation. Indeed, insomnia, depression, anxiety, or alcohol use have been associated with nightmares...

Cancer risk is influenced by inherited mutations, DNA replication errors, and environmental factors. However, the influence of genetic variation in immunosurveillance on cancer risk is not well understood. Leveraging population-level data from the UK Biobank and FinnGen, we show that heterozygosity at the human leukocyte antigen (HLA) -II loci is a...

Background Excessive daytime sleepiness (EDS), experienced in 10% to 20% of the population, has been associated with cardiovascular disease and death. However, the condition is heterogeneous and is prevalent in individuals having short and long sleep duration. We sought to clarify the relationship between sleep duration subtypes of EDS with cardiov...

Study objectives: Over 10% of the population in Europe and in the United States use sleep medication to manage sleep problems. Our objective was to elucidate genetic risk factors and clinical correlates that contribute to sleep medication purchase and estimate the comorbid impact of sleep problems. Methods: We performed epidemiological analysis...

Spouses may affect each other’s sleeping behaviour. In 47,420 spouse-pairs from the UK Biobank, we found a weak positive phenotypic correlation between spouses for self-reported sleep duration (r = 0.11; 95% CI = 0.10, 0.12) and a weak inverse correlation for chronotype (diurnal preference) (r = −0.11; −0.12, −0.10), which replicated in up to 127,0...

Raynaud's syndrome is a common dysautonomia where exposure to cold increases the vascular tone of distal arteries causing vasoconstriction and hypoxia particularly in the extremities. Current treatment options are limited and unspecific. Biological mechanisms leading to the phenotype remain uncharacterized. Using genetic and electronic health recor...

Myelination depends on the maintenance of oligodendrocytes that arise from oligodendrocyte precursor cells (OPCs). We show that OPC-specific proliferation, morphology, and BMAL1 are time-of-day dependent. Knockout of Bmal1 in mouse OPCs during development disrupts the expression of genes associated with circadian rhythms, proliferation, density, mo...

As suggested by previous research, sleep health is assumed to be a key determinant of future morbidity and mortality. In line with this, recent studies have found that poor sleep is associated with impaired cognitive function. However, to date, little is known about brain structural abnormalities underlying this association. Although recent finding...

Infections can lead to persistent or long-term symptoms and diseases such as shingles after varicella zoster, cancers after human papillomavirus, or rheumatic fever after streptococcal infections(1,2). Similarly, infection by SARS-CoV-2 can result in Long COVID, a condition characterized by symptoms of fatigue and pulmonary and cognitive dysfunctio...

Little is known regarding the shared genetic influences underlying the observed phenotypic association between chronotype and breast cancer in women. Leveraging summary statistics from the hitherto largest genome‐wide association study conducted in each trait, we investigated the genetic correlation, pleiotropic loci, and causal relationship of chr...

Background: Poor sleep is associated with an increased risk of infections and all-cause mortality but the causal direction between poor sleep and respiratory infections has remained unclear. We examined if poor sleep contributes as a causal risk factor to respiratory infections. Methods: We used data on insomnia, influenza and upper respiratory...

Background: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after d...

Polygenic risk scores (PRSs) estimate genetic liability for diseases and traits. However, the portability of PRSs in sleep traits has remained elusive. We generated PRSs for self-reported insomnia, chronotype and sleep duration using summary data from genome-wide association studies (GWASs) performed in 350,000 to 697,000 European-ancestry individu...

Background Sleep disturbance is common following hospitalisation both for COVID-19 and other causes. The clinical associations are poorly understood, despite it altering pathophysiology in other scenarios. We, therefore, investigated whether sleep disturbance is associated with dyspnoea along with relevant mediation pathways. Methods Sleep paramete...

Study Objectives Self-reported shorter/longer sleep duration, insomnia, and evening preference are associated with hyperglycaemia in observational analyses, with similar results observed in small studies using accelerometer-derived sleep traits. Mendelian randomization (MR) studies support an effect of self-reported insomnia, but not other sleep tr...

Rare variants in ten genes have been reported to cause Mendelian sleep conditions characterised by extreme sleep duration or timing. These include familial natural short sleep (ADRB1, DEC2/BHLHE41, GRM1 and NPSR1), advanced sleep phase (PER2, PER3, CRY2, CSNK1D and TIMELESS) and delayed sleep phase (CRY1). The association of variants in these genes...

Tuberculosis is a significant public health concern resulting in the death of over 1 million individuals each year worldwide. While treatment options and vaccines exist, a substantial number of infections still remain untreated or are caused by treatment resistant strains. Therefore, it is important to identify mechanisms that contribute to risk an...

Background Prostate cancer is highly heritable, with >250 common variants associated in genome-wide association studies. It commonly presents with non-specific lower urinary tract symptoms that are frequently associated with benign conditions. Methods Cohort study using UK Biobank data linked to primary care records. Participants were men with a r...

Purpose The study aimed to systematically ascertain male sex chromosome abnormalities, 47,XXY (Klinefelter syndrome [KS]) and 47,XYY, and characterize their risks of adverse health outcomes. Methods We analyzed genotyping array or exome sequence data in 207,067 men of European ancestry aged 40 to 70 years from the UK Biobank and related these to e...

Lyme disease is a tick-borne disease caused by bacteria of the genus Borrelia. The disease can initially manifest as an erythema migrans rash and, if able to evade the host immune defenses, can progress into a secondary stage chronic disease with debilitating physical or neurological manifestations1,2. The host factors that modulate susceptibility...

Myelination depends on maintenance of oligodendrocytes that arise from oligodendrocyte precursor cells (OPCs). We show that the dynamic nature of oligodendroglia and myelination are regulated by the circadian transcription factor BMAL1. Bmal1 knockdown in OPCs during development – but not adulthood – decreases OPC proliferation, whereas BMAL1 regul...

OBJECTIVE To examine the effects of sleep traits on glycated hemoglobin (HbA1c). RESEARCH DESIGN AND METHODS This study triangulated evidence across multivariable regression (MVR) and one- (1SMR) and two-sample Mendelian randomization (2SMR) including sensitivity analyses on the effects of five self-reported sleep traits (i.e., insomnia symptoms [...

Background Poor sleep is associated with an increased risk of infections and all-cause mortality, and acute sleep loss and disruption have been linked with inflammation and poorer immune control. Previous studies, however, have been unable to evidence causality between the chronic effects of poor sleep and respiratory infection risk. In light of th...

Tuberculosis is a significant public health concern resulting in the death of over 1 million individuals each year worldwide. While treatment options and vaccines exist, a substantial number of infections still remain untreated or are caused by treatment resistant strains. Therefore, it is important to identify mechanisms that contribute to risk an...

Objectives To assess how accurately a genetic risk score (GRS) can identify incident prostate cancer in men seeing their general practitioner with lower urinary tract symptoms. Design Cohort study. Setting UK Biobank data linked to primary care records. Participants Men registered with the UK Biobank, eligible for the primary care data linkage,...

Spouses may affect each other's sleeping behaviour. In 47,420 spouse-pairs from the UK Biobank, we found a weak positive phenotypic correlation between spouses for self-reported sleep duration (r=0.11; 95% CI=0.10, 0.12) and a weak inverse correlation for chronotype (diurnal preference) (r=-0.11; -0.12, -0.10), which replicated in up to 127,035 23a...

Congenital heart defects (CHD) are structural defects of the heart affecting approximately 1% of newborns. CHDs exhibit a complex inheritance pattern. While genetic factors are known to play an important role in the development of CHD, relatively few variants have been discovered so far and very few genome-wide association studies (GWAS) have been...

Rare variants in ten genes have been reported to cause Mendelian sleep conditions characterised by extreme sleep duration or timing. These include familial natural short sleep (ADRB1, DEC2/BHLHE41, GRM1 and NPSR1), advanced sleep phase (PER2, PER3, CRY2, CSNK1D and TIMELESS) and delayed sleep phase (CRY1). The association of variants of these genes...

Clinical classification is essential for estimating disease prevalence but is difficult, often requiring complex investigations. The widespread availability of population level genetic data makes novel genetic stratification techniques a highly attractive alternative. We propose a generalizable mathematical framework for determining disease prevale...

Late diurnal preference has been linked to poorer mental health outcomes, but the understanding of the causal role of diurnal preference on mental health and wellbeing is currently limited. Late diurnal preference is often associated with circadian misalignment (a mismatch between the timing of the endogenous circadian system and behavioural rhythm...

Background Sleep problems are both symptoms of and modifiable risk factors for many psychiatric disorders. Wrist-worn accelerometers enable objective measurement of sleep at scale. Here, we aimed to examine the association of accelerometer-derived sleep measures with psychiatric diagnoses and polygenic risk scores in a large community-based cohort....

Daytime napping is a common, heritable behavior, but its genetic basis and causal relationship with cardiometabolic health remain unclear. Here, we perform a genome-wide association study of self-reported daytime napping in the UK Biobank ( n = 452,633) and identify 123 loci of which 61 replicate in the 23andMe research cohort ( n = 541,333). Findi...

We aimed to obtain reliable reference charts for sleep duration, estimate the prevalence of sleep complaints across the lifespan and identify risk indicators of poor sleep. Studies were identified through systematic literature search in Embase, Medline and Web of Science (9 August 2019) and through personal contacts. Eligible studies had to be publ...

Objective To examine the effects of sleep traits on glycated haemoglobin (HbA1c). Design Observational multivariable regression (MVR), one-sample Mendelian randomization (1SMR), and two-sample summary data Mendelian randomization (2SMR). Setting UK Biobank (UKB) prospective cohort study and genome-wide association studies from the Meta-Analyses o...

Background It is established that Alzheimer’s disease (AD) patients experience sleep disruption. However, it remains unknown whether disruption in the quantity, quality or timing of sleep is a risk factor for the onset of AD. Methods We used the largest published genome-wide association studies of self-reported and accelerometer-measured sleep tra...

Background Single nucleotide polymorphism–based genetic risk scores (GRS) model genetic risk as a continuum and can discriminate coeliac disease but have not been validated in clinic. Human leukocyte antigen (HLA) DQ gene testing is available in clinic but does not include non‐HLA attributed risk and is limited by discrete risk stratification. Aim...

Background: Gastro-oesophageal reflux disease (GORD) is associated with multiple risk factors but determining causality is difficult. We used a genetic approach [Mendelian randomization (MR)] to identify potential causal modifiable risk factors for GORD. Methods: We used data from 451 097 European participants in the UK Biobank and defined GORD...

Daytime napping is a common, heritable behavior, but its genetic basis and causal relationship with cardiometabolic health remains unclear. Here, we performed a genome-wide association study of self-reported daytime napping in the UK Biobank (n=452,633) and identified 123 loci of which 60 replicated in 23andMe research participants (n=541,333). Fin...

Clinical classification is essential for estimating disease prevalence in a population but is difficult, often requiring complex investigations. The widespread availability of population level genetic data makes novel genetic stratification techniques a highly attractive alternative. We propose a generalizable mathematical framework for determining...

Urinary albumin-creatinine ratio is a marker of diabetic nephropathy and microvascular damage. Metabolic-related traits are observationally associated with ACR but their causal role is uncertain. Here, we confirmed ACR as a marker of microvascular damage and tested whether metabolic-related traits have causal relationships with ACR.The association...

Background: We assessed whether body mass index (BMI) affects social and socio-economic outcomes. Methods: We used Mendelian randomization (MR), non-linear MR and non-genetic and MR within-sibling analyses, to estimate relationships of BMI with six socio-economic and four social outcomes in 378 244 people of European ancestry in UK Biobank. Res...

Sleep is an essential human function but its regulation is poorly understood. Using accelerometer data from 85,670 UK Biobank participants, we perform a genome-wide association study of 8 derived sleep traits representing sleep quality, quantity and timing, and validate our findings in 5,819 individuals. We identify 47 genetic associations at P < 5...

Importance Insomnia, hypersomnia, and an evening chronotype are common in individuals with bipolar disorder (BD), but whether this reflects shared genetic liability is unclear. Stratifying by BD subtypes could elucidate this association and inform sleep and BD research. Objective To assess whether polygenic risk scores (PRSs) for sleep traits are...

Introduction Insomnia, hypersomnia and evening chronotype are common in bipolar disorder (BD) but research examining the role of genetics is mixed. Stratifying by bipolar subtypes could elucidate this relationship and inform sleep and BD research. Aim: to determine whether genetic liability to insomnia, hypersomnia and chronotype differ between bip...

Raised albumin-creatinine ratio (ACR) is an indicator of microvascular damage and renal disease. We aimed to identify genetic variants associated with raised ACR and study the implications of carrying multiple ACR-raising alleles with metabolic and vascular related disease. We performed a genome-wide association study of ACR using 437,027 individua...

Excessive daytime sleepiness (EDS) affects 10-20% of the population and is associated with substantial functional deficits. Here, we identify 42 loci for self-reported daytime sleepiness in GWAS of 452,071 individuals from the UK Biobank, with enrichment for genes expressed in brain tissues and in neuronal transmission pathways. We confirm the aggr...

Objective To examine whether sleep traits have a causal effect on risk of breast cancer. Design Mendelian randomisation study. Setting UK Biobank prospective cohort study and Breast Cancer Association Consortium (BCAC) case-control genome-wide association study. Participants 156 848 women in the multivariable regression and one sample mendelian...

Introduction Gastro-oesophageal Reflux Disease (GORD) is a common condition in which acid from the stomach leaks to the oesophagus causing heartburn and unpleasant taste in mouth, potentially leading to Barrett’s Oesophagus and Oesophageal Adenocarcinoma. Observationally, it has been reported that low body mass index (BMI), high BMI, past smoking,...

Introduction Specific HLA-DQ genes predispose to coeliac disease (CD) and HLA typing is occasionally used as a rule-out test in clinic. However, CD is polygenic and genome wide association studies (GWAS) have implicated ∼40 additional genetic variants. Using single nucleotide polymorphisms (SNPs) we aimed to combine all associated variants into a g...

Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association sign...

INTRODUCTION: It is established that Alzheimers disease (AD) patients experience sleep disruption. However, it remains unknown whether disruption in the quantity, quality or timing of sleep is a risk factor for the onset of AD. METHODS: Mendelian randomization (MR) was used to estimate the causal effect of self-reported and accelerometer-measured s...

Introduction Circadian rhythms have been implicated in breast cancer development. Individuals with a morning chronotype have been shown to have reduced risk of breast cancer (OR 0.88, 95% CI 0.82, 0.93 per category increase) using genetic data in Mendelian randomization (MR), which minimizes risk of reverse causation and confounding. However, univa...

The PERIOD2 (PER2) gene is a core molecular component of the circadian clock and plays an important role in the generation and maintenance of daily rhythms. Rs35333999, a missense variant of PER2 common in European populations, has been shown to associate with later chronotype. Chronotype relates to the timing of biological and behavioral activitie...

Sleep is an essential state of decreased activity and alertness but molecular factors regulating sleep duration remain unknown. Through genome-wide association analysis in 446,118 adults of European ancestry from the UK Biobank, we identify 78 loci for self-reported habitual sleep duration (p < 5 × 10⁻⁸; 43 loci at p < 6 × 10⁻⁹). Replication is obs...

Background Insomnia and hypersomnia are common in bipolar disorder (BD) but it is unclear whether genetic factors influence this association. Stratifying by bipolar subtypes could elucidate the nature of this association and inform research on sleep and BD. We therefore aimed to determine whether polygenic risk scores (PRS) for insomnia, daytime sl...