scholarly journals Clinical features of UK Biobank subjects carrying protein truncating variants in genes implicated in schizophrenia pathogenesis

2021 ◽  
Author(s):  
David Curtis
Keyword(s):  
Affective Disorders ◽  
Psychiatric Illness ◽  
Developmental Disorders ◽  
Visual Inspection ◽  
Psychotic Depression ◽  
Uk Biobank ◽  
Formal Statistical Analysis ◽  
Substantial Risk ◽  
The Uk ◽  
Automated Quality Control

AbstractThe SCHEMA consortium has identified ten genes in which protein truncating variants (PTVs) confer substantial risk of schizophrenia. Exome-sequenced participants in the UK Biobank who carried PTVs in these genes were studied to determine to what extent they demonstrated features of schizophrenia or had neuropsychiatric impairment. Following automated quality control and visual inspection of reads, 251 subjects were identified as having well-supported PTVs in one of these genes. The frequency of PTVs in CACNA1G was higher than had been observed in SCHEMA cases, casting doubt on its role in schizophrenia pathogenesis, but otherwise rates were similar to those observed in SCHEMA controls. Numbers were too small to allow formal statistical analysis but in general carriers of PTVs did not appear to have high rates of psychiatric illness or reduced educational or occupational functioning. One subject with a PTV in SETD1A had a diagnosis of schizophrenia. one with a PTV in HERC1 had psychotic depression and two subjects seemed to have developmental disorders, one with a PTV in GRIN2A and one with a PTV in RBCC1. There seemed to be somewhat increased rates of affective disorders among carriers of PTVs in HERC1 and RB1CC1. Carriers of PTVs did not appear to have subclinical manifestations of schizophrenia. Although PTVs in these genes can substantially increase schizophrenia risk, their effect seems to be dichotomous and most carriers appear psychiatrically well.This research has been conducted using the UK Biobank Resource.

scholarly journals Low birth weight and features of neuroticism and mood disorder in 83 545 participants of the UK Biobank cohort

BJPsych Open ◽  
2016 ◽  
Vol 2 (1) ◽  
pp. 38-44 ◽  
Author(s):  
Donald M. Lyall ◽  
Hazel M. Inskip ◽  
Daniel Mackay ◽  
Ian J. Deary ◽  
Andrew M. McIntosh ◽  
...  
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Affective Disorders ◽  
Very Low Birth Weight ◽  
Uk Biobank ◽  
Weight Category ◽  
Normal Birth ◽  
Eysenck Personality Inventory ◽  
Neuroticism Scale ◽  
The Uk

BackgroundLow birth weight has been inconsistently associated with risk of developing affective disorders, including major depressive disorder (MDD). To date, studies investigating possible associations between birth weight and bipolar disorder (BD), or personality traits known to predispose to affective disorders such as neuroticism, have not been conducted in large cohorts.AimsTo assess whether very low birth weight (<1500 g) and low birth weight (1500–2490 g) were associated with higher neuroticism scores assessed in middle age, and lifetime history of either MDD or BD. We controlled for possible confounding factors.MethodRetrospective cohort study using baseline data on the 83 545 UK Biobank participants with detailed mental health and birth weight data. Main outcomes were prevalent MDD and BD, and neuroticism assessed using the Eysenck Personality Inventory Neuroticism scale - Revised (EPIN-R)ResultsReferent to normal birth weight, very low/low birth weight were associated with higher neuroticism scores, increased MDD and BD. The associations between birth weight category and MDD were partially mediated by higher neuroticism.ConclusionsThese findings suggest that intrauterine programming may play a role in lifetime vulnerability to affective disorders.

scholarly journals Biological Insights Into Muscular Strength: Genetic Findings in the UK Biobank

2017 ◽  
Author(s):  
Emmi Tikkanen ◽  
Stefan Gustafsson ◽  
David Amar ◽  
Anna Shcherbina ◽  
Daryl Waggott ◽  
...  
Keyword(s):  
Grip Strength ◽  
Cognitive Performance ◽  
Muscular Strength ◽  
Developmental Disorders ◽  
Healthy Aging ◽  
Genetic Correlations ◽  
Hand Grip Strength ◽  
Uk Biobank ◽  
Hand Grip ◽  
The Uk

AbstractBackgroundHand grip strength, a simple indicator of muscular strength, has been associated with a range of health conditions, including fractures, disability, cardiovascular disease and premature death risk. Twin studies have suggested a high (50-60%) heritability, but genetic determinants are largely unknown.AimsIn this study, our aim was to study genetic variation associated with muscular strength in a large sample of 334,925 individuals of European descent from the UK Biobank, and to evaluate shared genetic aetiology with and causal effects of grip strength on physical and cognitive health.Methods and ResultsIn our discovery analysis of 223,315 individuals, we identified 101 loci associated with grip strength at genome-wide significance (P<5×10−8). Of these, 64 were associated (P<0.01 and consistent direction) also in the replication dataset (N=111,610). Many of the lead SNPs were located in or near genes known to have a function in developmental disorders (FTO, SLC39A8, TFAP2B, TGFA, CELF1, TCF4, BDNF, FOXP1, KIF1B, ANTXR2), and one of the most significant genes based on a gene-based analysis (ATP2A1) encodes SERCA1, the critical enzyme in calcium uptake to the sarcoplasmic reticulum, which plays a major role in muscle contraction and relaxation. Further, we demonstrated a significant enrichment of gene expression in brain-related transcripts among grip strength associations. Finally, we observed inverse genetic correlations of grip strength with cardiometabolic traits, and positive correlation with parents’ age of death and education; and showed that grip strength was causally related to fitness, physical activity and other indicators of frailty, including cognitive performance scores.ConclusionsIn our study of over 330,000 individuals from the general population, the genetic findings for hand grip strength suggest an important role of the central nervous system in strength performance. Further, our results indicate that maintaining good muscular strength is important for physical and cognitive performance and healthy aging.

Low birthweight is associated with poorer limb muscle mass and grip strength in middle age: findings from the UK Biobank Imaging Enhancement

2019 ◽  
Author(s):  
Elizabeth Curtis ◽  
Justin Liu ◽  
Kate Ward ◽  
Karen Jameson ◽  
Zahra Raisi-Estabragh ◽  
...  
Keyword(s):  
Grip Strength ◽  
Muscle Mass ◽  
Low Birthweight ◽  
Middle Age ◽  
Limb Muscle ◽  
Uk Biobank ◽  
The Uk

Contrasting Broad- and Clinically- defined Polygenic Indicators of Depression and Depression-related Phenotypes in Adults and Children

2020 ◽  
Author(s):  
John E. McGeary ◽  
Chelsie Benca-Bachman ◽  
Victoria Risner ◽  
Christopher G Beevers ◽  
Brandon Gibb ◽  
...  
Keyword(s):  
Suicidal Ideation ◽  
Cognitive Reappraisal ◽  
Twin Studies ◽  
European Ancestry ◽  
Summary Statistics ◽  
Depression Severity ◽  
Uk Biobank ◽  
Polygenic Scores ◽  
Adults And Children ◽  
The Uk

Twin studies indicate that 30-40% of the disease liability for depression can be attributed to genetic differences. Here, we assess the explanatory ability of polygenic scores (PGS) based on broad- (PGSBD) and clinical- (PGSMDD) depression summary statistics from the UK Biobank using independent cohorts of adults (N=210; 100% European Ancestry) and children (N=728; 70% European Ancestry) who have been extensively phenotyped for depression and related neurocognitive phenotypes. PGS associations with depression severity and diagnosis were generally modest, and larger in adults than children. Polygenic prediction of depression-related phenotypes was mixed and varied by PGS. Higher PGSBD, in adults, was associated with a higher likelihood of having suicidal ideation, increased brooding and anhedonia, and lower levels of cognitive reappraisal; PGSMDD was positively associated with brooding and negatively related to cognitive reappraisal. Overall, PGS based on both broad and clinical depression phenotypes have modest utility in adult and child samples of depression.

scholarly journals 699 Sleep Health Traits and COVID-19: Mortality Risk from the UK Biobank

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A273-A273
Author(s):  
Xi Zheng ◽  
Ma Cherrysse Ulsa ◽  
Peng Li ◽  
Lei Gao ◽  
Kun Hu
Keyword(s):  
Risk Factors ◽  
Sleep Apnea ◽  
Sleep Duration ◽  
Sex Education ◽  
Mortality Risk ◽  
Self Report ◽  
Severe Illness ◽  
Uk Biobank ◽  
Sleep Health ◽  
The Uk

Abstract Introduction While there is emerging evidence for acute sleep disruption in the aftermath of coronavirus disease 2019 (COVID-19), it is unknown whether sleep traits contribute to mortality risk. In this study, we tested whether earlier-life sleep duration, chronotype, insomnia, napping or sleep apnea were associated with increased 30-day COVID-19 mortality. Methods We included 34,711 participants from the UK Biobank, who presented for COVID-19 testing between March and October 2020 (mean age at diagnosis: 69.4±8.3; range 50.2–84.6). Self-reported sleep duration (less than 6h/6-9h/more than 9h), chronotype (“morning”/”intermediate”/”evening”), daytime dozing (often/rarely), insomnia (often/rarely), napping (often/rarely) and presence of sleep apnea (ICD-10 or self-report) were obtained between 2006 and 2010. Multivariate logistic regression models were used to adjust for age, sex, education, socioeconomic status, and relevant risk factors (BMI, hypertension, diabetes, respiratory diseases, smoking, and alcohol). Results The mean time between sleep measures and COVID-19 testing was 11.6±0.9 years. Overall, 5,066 (14.6%) were positive. In those who were positive, 355 (7.0%) died within 30 days (median = 8) after diagnosis. Long sleepers (&gt;9h vs. 6-9h) [20/103 (19.4%) vs. 300/4,573 (6.6%); OR 2.09, 95% 1.19–3.64, p=0.009), often daytime dozers (OR 1.68, 95% 1.04–2.72, p=0.03), and nappers (OR 1.52, 95% 1.04–2.23, p=0.03) were at greater odds of mortality. Prior diagnosis of sleep apnea also saw a two-fold increased odds (OR 2.07, 95% CI: 1.25–3.44 p=0.005). No associations were seen for short sleepers, chronotype or insomnia with COVID-19 mortality. Conclusion Data across all current waves of infection show that prior sleep traits/disturbances, in particular long sleep duration, daytime dozing, napping and sleep apnea, are associated with increased 30-day mortality after COVID-19, independent of health-related risk factors. While sleep health traits may reflect unmeasured poor health, further work is warranted to examine the exact underlying mechanisms, and to test whether sleep health optimization offers resilience to severe illness from COVID-19. Support (if any) NIH [T32GM007592 and R03AG067985 to L.G. RF1AG059867, RF1AG064312, to K.H.], the BrightFocus Foundation A2020886S to P.L. and the Foundation of Anesthesia Education and Research MRTG-02-15-2020 to L.G.

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