scholarly journals Obsessive–compulsive symptoms in a large population-based twin-family sample are predicted by clinically based polygenic scores and by genome-wide SNPs

2016 ◽  
Vol 6 (2) ◽  
pp. e731-e731 ◽  
Author(s):  
A den Braber ◽  
N R Zilhão ◽  
I O Fedko ◽  
J-J Hottenga ◽  
R Pool ◽  
...  
Keyword(s):  
Large Population ◽  
Population Based ◽  
Obsessive Compulsive ◽  
Obsessive Compulsive Symptoms ◽  
Genome Wide ◽  
Polygenic Scores ◽  
Family Sample

scholarly journals Phenotypic and genetic markers of psychopathology in a population-based sample of older adults

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Arianna M. Gard ◽  
Erin B. Ware ◽  
Luke W. Hyde ◽  
Lauren L. Schmitz ◽  
Jessica Faul ◽  
...  
Keyword(s):  
Older Adults ◽  
Large Population ◽  
The United States ◽  
Population Based ◽  
European Ancestry ◽  
Equation Modeling ◽  
General Factor ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Polygenic Scores

AbstractAlthough psychiatric phenotypes are hypothesized to organize into a two-factor internalizing–externalizing structure, few studies have evaluated the structure of psychopathology in older adults, nor explored whether genome-wide polygenic scores (PGSs) are associated with psychopathology in a domain-specific manner. We used data from 6003 individuals of European ancestry from the Health and Retirement Study, a large population-based sample of older adults in the United States. Confirmatory factor analyses were applied to validated measures of psychopathology and PGSs were derived from well-powered genome-wide association studies (GWAS). Genomic SEM was implemented to construct latent PGSs for internalizing, externalizing, and general psychopathology. Phenotypically, the data were best characterized by a single general factor of psychopathology, a factor structure that was replicated across genders and age groups. Although externalizing PGSs (cannabis use, antisocial behavior, alcohol dependence, attention deficit hyperactivity disorder) were not associated with any phenotypes, PGSs for major depressive disorder, neuroticism, and anxiety disorders were associated with both internalizing and externalizing phenotypes. Moreover, the variance explained in the general factor of psychopathology increased by twofold (from 1% to 2%) using the latent internalizing or latent one-factor PGSs, derived using weights from Genomic Structural Equation Modeling (SEM), compared with any of the individual PGSs. Collectively, results suggest that genetic risk factors for and phenotypic markers of psychiatric disorders are transdiagnostic in older adults of European ancestry. Alternative explanations are discussed, including methodological limitations of GWAS and phenotypic measurement of psychiatric outcome in large-scale population-based studies.

scholarly journals Prader–Willi syndrome, compulsive and ritualistic behaviours: the first population-based survey

2002 ◽  
Vol 180 (4) ◽  
pp. 358-362 ◽  
Author(s):  
D. J. Clarke ◽  
H. Boer ◽  
J. Whittington ◽  
A. Holland ◽  
J. Butler ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Rating Scales ◽  
Structured Interview ◽  
Population Based ◽  
Control Group ◽  
Prader Willi Syndrome ◽  
Obsessive Compulsive ◽  
Obsessive Compulsive Symptoms ◽  
Compulsive Disorder ◽  
Population Based Survey

BackgroundObsessive–compulsive disorder has been reported in association with Prader–Willi syndrome.AimsTo report the nature and prevalence of compulsive and similar symptoms associated with Prader–Willi syndrome in a population ascertained as completely as possible.MethodAttempted complete ascertainment of people with Prader– Willi syndrome in eight English counties. Administration of standardised rating scales and a structured interview. Comparison with people with learning disability and high body mass indices.ResultsPrader–Willi syndrome was associated with high rates of ritualistic behaviours, such as the need to ask or to tell something, insistence on routines, hoarding and ordering objects and repetitive actions and speech, compared with the control group, and was negatively correlated with IQ and socialisation age. Typical obsessive–compulsive symptoms, such as checking, counting and cleaning compulsions or obsessional thoughts, were not found.ConclusionsRitualistic and compulsive behaviours occur more frequently in association with Prader–Willi syndrome than among people with intellectual disability and significant obesity.

scholarly journals 85. GENOME-WIDE-ASSOCIATION AND POLYGENIC ARCHITECTURE OF SINGLE AND RECURRENT DEPRESSION EPISODES IN A LARGE POPULATION-BASED SAMPLE

2021 ◽  
Vol 51 ◽  
pp. e85-e86
Author(s):  
Thomas Als ◽  
Jakob Grove ◽  
Janne Thirstrup ◽  
Veera Rajagopal ◽  
Jonas Bybjerg-Grauholm ◽  
...  
Keyword(s):  
Large Population ◽  
Population Based ◽  
Genome Wide Association ◽  
Recurrent Depression ◽  
Genome Wide

scholarly journals Hematopoietic mosaic chromosomal alterations in the New England Centenarian Study

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 679-680
Author(s):  
Anastasia Leshchyk ◽  
Giulio Genovese ◽  
Stefano Monti ◽  
Thomas Perls ◽  
Paola Sebastiani
Keyword(s):  
New England ◽  
Neutral Loss ◽  
Large Population ◽  
Population Based ◽  
Steady Increase ◽  
Base Pairs ◽  
Chromosomal Alterations ◽  
Dna Microarray Data ◽  
R Ratio ◽  
Genome Wide

Abstract Mosaic chromosomal alterations (mCAs) are structural alterations that include deletions, duplications, or copy-neutral loss of heterozygosity. mCAs are reported to be associated with survival, age, cancer, and cardiovascular disease. Previous studies of mCAs in large population-based cohorts (UK Biobank, MGBB, BioBank Japan, and FinnGen) have demonstrated a steady increase of mCAs as people age. The distribution of mCAs in centenarians and their offspring is not well characterized. We applied MOsaic CHromosomal Alteration (MoChA) caller on 2298 genome-wide genotype samples of 1582 centenarians, 443 centenarians’ offspring, and 273 unrelated controls from the New England Centenarian Study (NECS). Integrating Log R ratio and B-allele frequency (BAF) intensities with genotype phase information, MoChA employs a Hidden Markov Model to detect mCA-induced deviations in allelic balance at heterozygous sites consistent with genotype phase in the DNA microarray data. We analyzed mCAs spanning over 100 k base pairs, with an estimated cell fraction less than 50%, within samples with genome-wide BAF phase concordance across phased heterozygous sites less than 0.51, and with LOD score of more than 10 for the model based on BAF and genotype phase. Our analysis showed that somatic mCAs increase with older age up to approximately 102 years, but the prevalence of the subjects with mCAs tend to decrease after that age, thus suggesting that accumulation of mCAs is less prevalent in long-lived individuals. We also used Poisson regression to show that centenarians and their offspring tend to accumulate less mCA (RR = 0.63, p=0.045) compared to the controls.

Economics and Genetics

2018 ◽  
Author(s):  
Jason M. Fletcher
Keyword(s):  
Big Data ◽  
Genetic Information ◽  
Predictive Power ◽  
Large Population ◽  
Population Based ◽  
Genetic Effects ◽  
Rapid Expansion ◽  
Economic Research ◽  
Polygenic Scores ◽  
Small Genetic Effects

Two interrelated advances in genetics have occurred which have ushered in the growing field of genoeconomics. The first is a rapid expansion of so-called big data featuring genetic information collected from large population–based samples. The second is enhancements to computational and predictive power to aggregate small genetic effects across the genome into single summary measures called polygenic scores (PGSs). Together, these advances will be incorporated broadly with economic research, with strong possibilities for new insights and methodological techniques.

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 Shared genetic etiology between obsessive-compulsive disorder, obsessive-compulsive symptoms in the population, and insulin signaling

2019 ◽  
Author(s):  
Janita Bralten ◽  
Joanna Widomska ◽  
Ward De Witte ◽  
Dongmei Yu ◽  
Carol A. Mathews ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Obsessive Compulsive Disorder ◽  
Insulin Signaling ◽  
Population Based ◽  
Obsessive Compulsive ◽  
Genetic Etiology ◽  
Obsessive Compulsive Symptoms ◽  
Gene Set ◽  
Compulsive Disorder ◽  
Shared Genetic

AbstractObjectiveObsessive-compulsive symptoms (OCS) in the population have been linked to obsessive-compulsive disorder (OCD) in genetic and epidemiological studies. Insulin signaling has been implicated in OCD. We extend previous work by assessing genetic overlap between OCD, population-based OCS, and central nervous system (CNS) and peripheral insulin signaling.MethodsWe conducted genome-wide association studies (GWASs) in the population-based Philadelphia Neurodevelopmental Cohort (PNC, 650 children and adolescents) of the total OCS score and six OCS factors from an exploratory factor analysis of 22 questions. Subsequently, we performed polygenic risk score (PRS) analysis to assess shared genetic etiologies between clinical OCD (using GWAS data from the Psychiatric Genomics Consortium), the total OCS score and OCS factors. We then performed gene-set analyses with a set of OCD-linked genes centered around CNS insulin-regulated synaptic function and PRS analyses for five peripheral insulin signaling-related traits. For validation purposes, we explored data from the independent Spit for Science population cohort (5047 children and adolescents).ResultsIn the PNC, we found a shared genetic etiology between OCD and ‘impairment’, ‘contamination/cleaning’ and ‘guilty taboo thoughts’. In the Spit for Science cohort, we were able to validate the finding for ‘contamination/cleaning’, and additionally observed genetic sharing between OCD and ‘symmetry/counting/ordering’. The CNS insulin-linked gene-set associated with ‘symmetry/counting/ordering’. We also identified genetic sharing between peripheral insulin signaling-related traits (type 2 diabetes and the blood levels of HbA1C, fasting insulin and 2 hour glucose) and OCD as well as certain OCS.ConclusionsOCD, OCS in the population and insulin-related traits share genetic risk factors, indicating a common etiological mechanism underlying somatic and psychiatric disorders.

scholarly journals Psychiatric research platform within SAIL - Linkage of prospectively ascertained phenotypically rich and genetic data to routinely collected anonymised records.

2017 ◽  
Vol 1 (1) ◽  
Author(s):  
Joanna McGregor ◽  
Ann John ◽  
Keith Lloyd
Keyword(s):  
Mental Health ◽  
Health Research ◽  
Large Population ◽  
Genetic Data ◽  
Population Based ◽  
Mental Health Research ◽  
Response To Treatment ◽  
Psychiatric Research ◽  
Illness Onset ◽  
Polygenic Scores

ABSTRACT ObjectivesWe have conducted a feasibility study linking clinically rich survey data to routine data to create a platform for psychosis research in Wales: K Lloyd et al (2015), A national population-based e-cohort of people with psychosis (PsyCymru) linking prospectively ascertained phenotypically rich and genetic data to routinely collected records: overview, recruitment and linkage, Schizophrenia Research. Now we expand upon this through the linkage of large clinically rich cohorts with a range of mental health diagnoses along with genetic data to conduct validation exercises, develop novel methodologies, assess genetic and environment interactions and outcomes and address hypothesis-driven research questions. ApproachThrough collaborations between the Farr Institute, Cardiff University based MRC centre for Neuropsychiatric Genetics and Genomics and the National Centre for Mental Health (NCMH) clinically rich data and genetic (CNVs, SNPs & polygenic scores) data from around 6000+ participants recruited from a variety of mental health research studies including ‘PsyCymru’, ‘Genetic susceptibility to cognitive deficits study and NCMH amongst others will be loaded and linked to the datasets within SAIL. The analysis plan would firstly include validation exercises to compare the data between sources. Methodologies would be developed using this data to determine illness onset, relapse, chronicity, severity and response to treatment applied to large population-based mental health e-cohorts. ResultsBy pooling together health service data, genetic variants, environmental and lifestyle factors, phenotypic and endo-phenotypic (cognitive scores) along with the ability to ascertain temporal relationships afforded by the longitudinal perspective available in SAIL we may be able to evaluate potential risk factors, assess the complex GxE interactions that lead to disease progression, and assess outcomes such as prognosis, remission, relapse and premature mortality. The on-going routine updates provide us with the opportunity to follow-up these individuals across multiple health care settings in a cost effective and in-obtrusive manner and to carry out health services utilization/benefit and treatment surveillance in a naturalistic setting. This resource will continue to expand over the coming years in size, breadth and depth of data, with continued recruitment and additional measures planned. ConclusionTo advance mental health research by developing our understanding of the causes, course and outcomes of mental illness that may lead to the development of better diagnostic classification, predictive, preventative strategies and therapeutic approaches.

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