scholarly journals Molecular Genetic Risk for Psychosis Is Associated With Psychosis Risk Symptoms in a Population-Based UK Cohort: Findings From Generation Scotland

2020 ◽  
Vol 46 (5) ◽  
pp. 1045-1052
Author(s):  
Anna R Docherty ◽  
Andrey A Shabalin ◽  
Daniel E Adkins ◽  
Frank Mann ◽  
Robert F Krueger ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Molecular Genetic ◽  
Large Population ◽  
Genetic Data ◽  
Population Based ◽  
Health Study ◽  
Polygenic Risk ◽  
Generation Scotland ◽  
Common Genetic Variants ◽  
Psychosis Risk

Abstract Objective Subthreshold psychosis risk symptoms in the general population may be associated with molecular genetic risk for psychosis. This study sought to optimize the association of risk symptoms with genetic risk for psychosis in a large population-based cohort in the UK (N = 9104 individuals 18–65 years of age) by properly accounting for population stratification, factor structure, and sex. Methods The newly expanded Generation Scotland: Scottish Family Health Study includes 5391 females and 3713 males with age M [SD] = 45.2 [13] with both risk symptom data and genetic data. Subthreshold psychosis symptoms were measured using the Schizotypal Personality Questionnaire-Brief (SPQ-B) and calculation of polygenic risk for schizophrenia was based on 11 425 349 imputed common genetic variants passing quality control. Follow-up examination of other genetic risks included attention-deficit hyperactivity disorder (ADHD), autism, bipolar disorder, major depression, and neuroticism. Results Empirically derived symptom factor scores reflected interpersonal/negative symptoms and were positively associated with polygenic risk for schizophrenia. This signal was largely sex specific and limited to males. Across both sexes, scores were positively associated with neuroticism and major depressive disorder. Conclusions A data-driven phenotypic analysis enabled detection of association with genetic risk for schizophrenia in a population-based sample. Multiple polygenic risk signals and important sex differences suggest that genetic data may be useful in improving future phenotypic risk assessment.

scholarly journals Subthreshold psychosis symptoms associated with molecular genetic risk in a population-based cohort: Findings from Generation Scotland

2019 ◽  
Author(s):  
A.R. Docherty ◽  
Andrey A. Shabalin ◽  
Daniel E. Adkins ◽  
Frank Mann ◽  
Robert F. Krueger ◽  
...  
Keyword(s):  
Sex Differences ◽  
General Population ◽  
Genetic Risk ◽  
Molecular Genetic ◽  
Population Based ◽  
Risk Scores ◽  
Factor Scores ◽  
Polygenic Risk ◽  
Genome Wide ◽  
Genetic Risks

AbstractImportanceSubthreshold psychosis symptoms in the general population may be associated with genetic risk for schizophrenia. In this analysis, empirically-derived symptom factor scores led to a detection of significant and robust polygenic signal.ObjectiveThis study sought to optimize genetic association with data-driven symptom factor scores, accounting for cohort factor structure and sex differences.DesignEFA-derived symptom factor scores were regressed onto PRS for schizophrenia in models accounting for age and genetic ancestry principal components. Follow-up examination of symptom factor score associations with other related genetic risks included ADHD, autism, bipolar disorder, major depression, and neuroticism.ParticipantsThis study examined the newly expanded symptom dataset from the Northern European ancestry cohort, Generation Scotland: Scottish Family Health Study (N = 9,105 individuals 18-65 years of age) comprising common variant and subthreshold psychosis symptom data. A total of 5,391 females and 3,713 males with age M[SD] = 45.2 [13] were included in the final analyses.Main Outcome and MeasureSubthreshold psychosis symptoms were measured using the Schizotypal Personality Questionnaire-Brief (SPQ-B). Primary phenotypic factor scores and genome-wide polygenic risk scores (PRS) reflected weighted sum scores and were examined as continuous measures. Polygenic risk scores were calculated from genome-wide association summary statistics using 7,358,674 imputed common genetic variants passing quality control.ResultsIn males, symptom factor scores were positively associated with polygenic risk for schizophrenia alone and implicated primarily interpersonal/negative symptoms. In females, symptom factor scores were positively associated with polygenic risks for ADHD and autism but not schizophrenia. Scores were robustly associated with genetic risk for neuroticism across both males and females.Conclusions and RelevanceThis study detected a significant association of subthreshold psychosis symptoms with genetic risk for schizophrenia and neuroticism in a population-based sample. Furthermore, important sex differences suggest a need for better understanding of schizophrenia risk assessment in females.Key PointsQuestionWhat molecular genetic risks are associated with subthreshold psychosis symptoms in the general population?FindingsIn a large population-based cohort (N = 9,084), significant associations of polygenic risks with symptoms were observed. Symptoms were associated with genetic risk for schizophrenia in males, for ADHD and autism spectrum disorder in females, and for neuroticism across both males and females.MeaningAssociations of genetic risk with symptoms in the general population are highly significant and suggest important sex differences.

scholarly journals Independent and combined associations between fast-food outlet exposure and genetic risk for obesity: a population-based, cross-sectional study in the UK

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Thomas Burgoine ◽  
Pablo Monsivais ◽  
Stephen J. Sharp ◽  
Nita G. Forouhi ◽  
Nicholas J. Wareham
Keyword(s):  
Genetic Risk ◽  
Fast Food ◽  
Genetic Risk Score ◽  
Population Based ◽  
Overweight And Obesity ◽  
Nucleotide Polymorphisms ◽  
Food Outlet ◽  
Cross Sectional ◽  
Fast Food Outlet ◽  
Common Genetic Variants

Abstract Background Characteristics of the built environment, such as neighbourhood fast-food outlet exposure, are increasingly recognised as risk factors for unhealthy diet and obesity. Obesity also has a genetic component, with common genetic variants explaining a substantial proportion of population-level obesity susceptibility. However, it is not known whether and to what extent associations between fast-food outlet exposure and body weight are modified by genetic predisposition to obesity. Methods We used data from the Fenland Study, a population-based sample of 12,435 UK adults (mean age 48.6 years). We derived a genetic risk score associated with BMI (BMI-GRS) from 96 BMI-associated single nucleotide polymorphisms. Neighbourhood fast-food exposure was defined as quartiles of counts of outlets around the home address. We used multivariable regression models to estimate the associations of each exposure, independently and in combination, with measured BMI, overweight and obesity, and investigated interactions. Results We found independent associations between BMI-GRS and risk of overweight (RR = 1.34, 95% CI 1.23–1.47) and obesity (RR = 1.73, 95% CI 1.55–1.93), and between fast-food outlet exposure and risk of obesity (highest vs lowest quartile RR = 1.58, 95% CI 1.21–2.05). There was no evidence of an interaction of fast-food outlet exposure and genetic risk on BMI (P = 0.09), risk of overweight (P = 0.51), or risk of obesity (P = 0.27). The combination of higher BMI-GRS and highest fast-food outlet exposure was associated with 2.70 (95% CI 1.99–3.66) times greater risk of obesity. Conclusions Our study demonstrated independent associations of both genetic obesity risk and neighbourhood fast-food outlet exposure with adiposity. These important drivers of the obesity epidemic have to date been studied in isolation. Neighbourhood fast-food outlet exposure remains a potential target of policy intervention to prevent obesity and promote the public’s health.

Epidemiologic study of risk factors for meningioma in the Mayo Clinic Study of Aging.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2067-2067
Author(s):  
Alissa Butts ◽  
Jeremy A. Syrjanen ◽  
Jeremiah Aakre ◽  
Paul D. Brown ◽  
Clifford R. Jack ◽  
...  
Keyword(s):  
Risk Factors ◽  
Mayo Clinic ◽  
Large Population ◽  
Epidemiologic Study ◽  
Significant Risk ◽  
Female Gender ◽  
Population Based ◽  
Continuous Variable ◽  
Health Study ◽  
Clinic Study

2067 Background: An estimated 2% of the general population has a meningioma (Vernooij et al. 2007), which accounts for about 36% of all primary intracranial tumors (Ostrom et al. 2015). The most established risk factors are older age and female gender. One small study identified gender but no other risk factors with meningioma (Krampla et al 2004). A larger study using the Iowa Women’s Health study data found lower levels of physical activity, greater body mass index (BMI), greater height and uterine fibroids were associated with meningioma (Johnson et al. 2011). We sought to replicate these findings and to identify additional risk factors related to meningioma in a large population-based sample. Methods: Study participants were enrolled in the Mayo Clinic Study of Aging (MCSA), a population-based sample of Olmsted County, Minnesota residents used to study prevalence, incidence, and risk-factors for Mild Cognitive Impairment and dementia and includes a variety of medical factors. Using a text search of radiologists’ notes of 2,402 MCSA individuals, mean age 77±8 years and scanned between 2004-2014.We identified 52 subjects who had at least one meningioma. We estimated the association of selected potential risk factors with presence of meningioma using odds ratios and 95% confidence intervals from logistic regression models adjusted for age and gender, which informed the multivariable models. Results: In the initial models, significant risk factors identified included BMI (as a continuous variable) (OR = 1.06 95%CI 1.01 to 1.12), taking NSAIDS (OR = 2.11, 95%CI 1.13 to 3.95), aspirin (OR = 1.90, 95%CI 1.04 to 3.46), and blood pressure lowering medication (OR = 2.06, 95%CI 1.07 to 3.99). Protective factors included male gender (OR = 0.51, 95%CI 0.29 to 0.90), coronary artery disease (CAD; OR = 0.46, 95%CI 0.22 to 0.97) and higher Beck Anxiety Inventory (BAI) total score (OR = 0.88, 95%CI 0.78 to 0.98). Simultaneous adjustment for these factors in a multivariable model did not attenuate these associations. Conclusions: Findings reveal gender and BMI as risk factors for meningioma. Additionally, certain medications such as NSAIDS and BP lowering medications warrant follow up as potential factors related to development of meningioma.

scholarly journals Electronic health record and genome-wide genetic data in Generation Scotland participants

2017 ◽  
Vol 2 ◽  
pp. 85 ◽  
Author(s):  
Shona M. Kerr ◽  
Archie Campbell ◽  
Jonathan Marten ◽  
Veronique Vitart ◽  
Andrew M McIntosh ◽  
...  
Keyword(s):  
Electronic Health Record ◽  
Genetic Data ◽  
Health Study ◽  
Index Number ◽  
Health Record ◽  
Real World Data ◽  
Public Health Importance ◽  
Genome Wide ◽  
Generation Scotland ◽  
Electronic Health

This article provides the first detailed demonstration of the research value of the Electronic Health Record (EHR) linked to research data in Generation Scotland Scottish Family Health Study (GS:SFHS) participants, together with how to access this data. The structured, coded variables in the routine biochemistry, prescribing and morbidity records, in particular, represent highly valuable phenotypic data for a genomics research resource. Access to a wealth of other specialized datasets, including cancer, mental health and maternity inpatient information, is also possible through the same straightforward and transparent application process. The EHR linked dataset is a key component of GS:SFHS, a biobank conceived in 1999 for the purpose of studying the genetics of health areas of current and projected public health importance. Over 24,000 adults were recruited from 2006 to 2011, with broad and enduring written informed consent for biomedical research. Consent was obtained from 23,603 participants for GS:SFHS study data to be linked to their Scottish National Health Service (NHS) records, using their Community Health Index number. This identifying number is used for NHS Scotland procedures (registrations, attendances, samples, prescribing and investigations) and allows healthcare records for individuals to be linked across time and location. Here, we describe the NHS EHR dataset on the sub-cohort of 20,032 GS:SFHS participants with consent and mechanism for record linkage plus extensive genetic data. Together with existing study phenotypes, including family history and environmental exposures, such as smoking, the EHR is a rich resource of real world data that can be used in research to characterise the health trajectory of participants, available at low cost and a high degree of timeliness, matched to DNA, urine and serum samples and genome-wide genetic information.

scholarly journals 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

2016 ◽  
Author(s):  
LB Navrady ◽  
SJ Ritchie ◽  
SWY Chan ◽  
DM Kerr ◽  
MJ Adams ◽  
...  
Keyword(s):  
Psychological Distress ◽  
Significant Interaction ◽  
Protective Factor ◽  
Short Form ◽  
Family Health ◽  
Population Based ◽  
Depressive Illness ◽  
Health Study ◽  
Uk Biobank ◽  
Generation Scotland

ABSTRACTBackgroundNeuroticism 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.MethodsAssociations 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.ResultsNeuroticism 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: ß = -0.05, p < .01; UK Biobank: ß = -0.02, p < .01), such that intelligence protected against the deleterious effect of neuroticism on psychological distress.ConclusionsFrom 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.

scholarly journals Two schizophrenia imaging signatures and their associations with cognition, psychopathology, and genetics in the general population

2022 ◽  
Author(s):  
Ganesh B Chand ◽  
Pankhuri Singhal ◽  
Dominic B Dwyer ◽  
Junhao Wen ◽  
Guray Erus ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Gray Matter Volume ◽  
Control Sample ◽  
Population Level ◽  
Population Based ◽  
Risk Scores ◽  
Support Vector ◽  
Cross Sectional ◽  
Polygenic Risk ◽  
Independent Population

The prevalence and significance of schizophrenia-related phenotypes at the population-level are debated in the literature. Here we assess whether two recently reported neuroanatomical signatures of schizophrenia, signature 1 with widespread reduction of gray matter volume, and signature 2 with increased striatal volume, could be replicated in an independent schizophrenia sample, and investigate whether expression of these signatures can be detected at the population-level and how they relate to cognition, psychosis spectrum symptoms, and schizophrenia genetic risk. This cross-sectional study used an independent schizophrenia-control sample (n=347; age 16-57 years) for replication of imaging signatures, and then examined two independent population-level datasets: Philadelphia Neurodevelopmental Cohort [PNC; n=359 typically developing (TD) and psychosis-spectrum symptoms (PS) youth] and UK Biobank (UKBB; n=836; age 44-50 years) adults. We quantified signature expression using support-vector machine learning, and compared cognition, psychopathology, and polygenic risk between signatures. Two neuroanatomical signatures of schizophrenia were replicated. Signature 1 but not signature 2 was significantly more common in youth with PS than TD youth, whereas signature 2 frequency was similar. In both youth and adults, signature 1 had worse cognitive performance than signature 2. Compared to adults with neither signature, adults expressing signature 1 had elevated schizophrenia polygenic risk scores, but this was not seen for signature 2. We successfully replicate two neuroanatomical signatures of schizophrenia, and describe their prevalence in population-based samples of youth and adults. We further demonstrate distinct relationships of these signatures with psychosis symptoms, cognition, and genetic risk, potentially reflecting underlying neurobiological vulnerability.

scholarly journals Intelligence and neuroticism in relation to depression and psychological distress: Evidence from two large population cohorts

2017 ◽  
Vol 43 ◽  
pp. 58-65 ◽  
Author(s):  
L.B. Navrady ◽  
S.J. Ritchie ◽  
S.W.Y. Chan ◽  
D.M. Kerr ◽  
M.J. Adams ◽  
...  
Keyword(s):  
Psychological Distress ◽  
Protective Factor ◽  
Short Form ◽  
Large Population ◽  
Family Health ◽  
Population Based ◽  
Health Study ◽  
Increased Risk ◽  
Ability Tests ◽  
Risk For Depression

AbstractBackground: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.

Antiphospholipid antibodies in a large population-based cohort: genome-wide associations and effects on monocyte gene expression

2016 ◽  
Vol 116 (07) ◽  
pp. 115-123 ◽  
Author(s):  
Nadine Müller-Calleja ◽  
Heidi Rossmann ◽  
Christian Müller ◽  
Philipp Wild ◽  
Stefan Blankenberg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Antiphospholipid Antibodies ◽  
Ex Vivo ◽  
Genetic Locus ◽  
Large Population ◽  
Population Based ◽  
Chromosome 17 ◽  
Health Study ◽  
Genome Wide

SummaryThe antiphospholipid syndrome (APS) is characterised by venous and/ or arterial thrombosis and pregnancy morbidity in women combined with the persistent presence of antiphospholipid antibodies (aPL). We aimed to identify genetic factors associated with the presence of aPL in a population based cohort. Furthermore, we wanted to clarify if the presence of aPL affects gene expression in circulating monocytes. Titres of IgG and IgM against cardiolipin, D2glycoprotein 1 (antiD2GPI), and IgG against domain 1 of D2GPI (anti-domain 1) were determined in approx. 5,000 individuals from the Gutenberg Health Study (GHS) a population based cohort of German descent. Genotyping was conducted on Affymetrix Genome-Wide Human SNP 6.0 arrays. Monocyte gene expression was determined in a subgroup of 1,279 individuals by using the Illumina HT-12 v3 BeadChip. Gene expression data were confirmed in vitro and ex vivo by qRT-PCR. Genome wide analysis revealed significant associations of anti-D2GPI IgG and APOH on chromosome 17, which had been previously identified by candidate gene approaches, and of anti-domain1 and MACROD2 on chromosome 20 which has been listed in a previous GWAS as a suggestive locus associated with the occurrence of anti-D2GPI antibodies. Expression analysis confirmed increased expression of TNFD in monocytes and identified and confirmed neuron navigator 3 (NAV3) as a novel gene induced by aPL. In conclusion, MACROD2 represents a novel genetic locus associated with aPL. Furthermore, we show that aPL induce the expression of NAV3 in monocytes and endothelial cells. This will stimulate further research into the role of these genes in the APS.

scholarly journals Sources of variation in nutrient intakes among men in Shanghai, China

2005 ◽  
Vol 8 (8) ◽  
pp. 1293-1299 ◽  
Author(s):  
Hui Cai ◽  
Gong Yang ◽  
Yong-Bing Xiang ◽  
James R Hebert ◽  
Da-Ke Liu ◽  
...  
Keyword(s):  
Dietary Intake ◽  
Total Variation ◽  
Large Population ◽  
Population Based ◽  
Health Study ◽  
Random Errors ◽  
Chinese Men ◽  
Epidemiological Risk ◽  
The Usa ◽  
Variance Ratios

AbstractBackground and objectiveRandom errors, from any source, will attenuate epidemiological risk estimates. Before we launched the Shanghai Men's Health Study (SMHS), a large population-based cohort study investigating the diet–cancer association among Chinese men, a dietary calibration study was conducted among 96 men aged 40–75 years (mean age 56.5 years), with biweekly 24-hour dietary recalls (24HDRs) implemented over a 1-year period. Data from this study were analysed to evaluate the nature and magnitude of variances for intake of 26 nutrients among SMHS participants, to compare variance ratios of 26 nutrients among Chinese men and women and individuals in other studies, and to estimate the number of 24HDRs required for future dietary calibration studies in similar populations.DesignNinety-six healthy, free-living men in Shanghai were administered biweekly 24HDR interviews 24 times over a 1-year period. To assess between-individual and within-individual contributions to variance, a mixed effects model was fitted and ratios of within-individual to between-individualdietary intake variances were computed.SettingShanghai, China.ResultsIn agreement with reports from studies conducted in the USA and many other countries, we found that within-individual variances were usually larger than between-individual variances in dietary intake for all nutrients. The sum of all other variation (e.g. weekday and weekend, seasonal, interviewer) accounted for less than 5% of total variation. Ratios of within- to between-individual variances (for log-transformed data) ranged from 1.25 for carbohydrate intake to near 8 for δ-tocopherol intake.ConclusionsThe results of this study suggest that among middle-aged and elderly Chinese men in Shanghai, within- and between-individual variation account for more than 95% of the total variation for 26 nutrients. Further dietary validation studies in the same population could be adequately carried out with only 12 days of dietary recalls, if 100 participants were enrolled.

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