scholarly journals Using the UK Biobank as a global reference of worldwide populations: application to measuring ancestry diversity from GWAS summary statistics

2021 ◽  
Author(s):  
Florian Privé
Keyword(s):  
Genetic Diversity ◽  
Cohort Study ◽  
Summary Statistics ◽  
Uk Biobank ◽  
Reference Groups ◽  
Phenotypic Data ◽  
The United Kingdom ◽  
Four Corners ◽  
The World ◽  
The Uk

The UK Biobank project is a prospective cohort study with deep genetic and phenotypic data collected on almost 500,000 individuals from across the United Kingdom. Within this dataset, we carefully define 17 distinct ancestry groups from all four corners of the world. Using allele frequencies derived from these global reference groups, we are now able to effectively measure diversity from summary statistics of any genetic dataset. Measuring genetic diversity is an important problem because increasing genetic diversity is key to making new genetic discoveries, while also being a major source of confounding to be aware of in genetics studies.

scholarly journals Can a data driven obesity classification system identify those at risk of severe COVID-19 in the UK Biobank cohort study?

2021 ◽  
Author(s):  
Stephen Clark ◽  
Michelle Morris ◽  
Nik Lomax ◽  
Mark Birkin
Keyword(s):  
Cohort Study ◽  
United Kingdom ◽  
Classification System ◽  
Holistic Approach ◽  
Data Driven ◽  
Uk Biobank ◽  
The United Kingdom ◽  
The Individual ◽  
The Uk

AbstractCOVID-19 is a disease that has been shown to have outcomes that vary by certain socio-demographic and socio-economic groups. It is increasingly important that an understanding of these outcomes should be derived not from the consideration of one aspect, but by a more multi-faceted understanding of the individual. In this study use is made of a recent obesity driven classification of participants in the United Kingdom Biobank (UKB) to identify trends in COVID-19 outcomes. This classification is informed by a recently created obesity systems map, and the COVID-19 outcomes are: undertaking a test, a positive test, hospitalisation and mortality. It is demonstrated that the classification is able to identify meaningful differentials in these outcomes. This more holistic approach is recommended for identification and prioritisation of COVID-19 risk and possible long-COVID determination.

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 Clinical laboratory tests and five-year incidence of major depressive disorder: a prospective cohort study of 433,890 participants from the UK Biobank

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michael Wainberg ◽  
Stefan Kloiber ◽  
Breno Diniz ◽  
Roger S. McIntyre ◽  
Daniel Felsky ◽  
...  
Keyword(s):  
Public Health ◽  
Major Depressive Disorder ◽  
Cohort Study ◽  
Confidence Interval ◽  
Depressive Disorder ◽  
Blood Cell ◽  
Biological Processes ◽  
Uk Biobank ◽  
Major Depressive ◽  
The Uk

AbstractPrevention of major depressive disorder (MDD) is a public health priority. Identifying biomarkers of underlying biological processes that contribute to MDD onset may help address this public health need. This prospective cohort study encompassed 383,131 white British participants from the UK Biobank with no prior history of MDD, with replication in 50,759 participants of other ancestries. Leveraging linked inpatient and primary care records, we computed adjusted odds ratios for 5-year MDD incidence among individuals with values below or above the 95% confidence interval (<2.5th or >97.5th percentile) on each of 57 laboratory measures. Sensitivity analyses were performed across multiple percentile thresholds and in comparison to established reference ranges. We found that indicators of liver dysfunction were associated with increased 5-year MDD incidence (even after correction for alcohol use and body mass index): elevated alanine aminotransferase (AOR = 1.35, 95% confidence interval [1.16, 1.58]), aspartate aminotransferase (AOR = 1.39 [1.19, 1.62]), and gamma glutamyltransferase (AOR = 1.52 [1.31, 1.76]) as well as low albumin (AOR = 1.28 [1.09, 1.50]). Similar observations were made with respect to endocrine dysregulation, specifically low insulin-like growth factor 1 (AOR = 1.34 [1.16, 1.55]), low testosterone among males (AOR = 1.60 [1.27, 2.00]), and elevated glycated hemoglobin (HbA1C; AOR = 1.23 [1.05, 1.43]). Markers of renal impairment (i.e. elevated cystatin C, phosphate, and urea) and indicators of anemia and macrocytosis (i.e. red blood cell enlargement) were also associated with MDD incidence. While some immune markers, like elevated white blood cell and neutrophil count, were associated with MDD (AOR = 1.23 [1.07, 1.42]), others, like elevated C-reactive protein, were not (AOR = 1.04 [0.89, 1.22]). The 30 significant associations validated as a group in the multi-ancestry replication cohort (Wilcoxon p = 0.0005), with a median AOR of 1.235. Importantly, all 30 significant associations with extreme laboratory test results were directionally consistent with an increased MDD risk. In sum, markers of liver and kidney dysfunction, growth hormone and testosterone deficiency, innate immunity, anemia, macrocytosis, and insulin resistance were associated with MDD incidence in a large community-based cohort. Our results support a contributory role of diverse biological processes to MDD onset.

scholarly journals Hormonal and reproductive factors and risk of upper gastrointestinal cancers in men: A prospective cohort study within the UK Biobank

2018 ◽  
Vol 143 (4) ◽  
pp. 831-841
Author(s):  
Úna C. Mc Menamin ◽  
Andrew T. Kunzmann ◽  
Michael B. Cook ◽  
Brian T. Johnston ◽  
Liam J. Murray ◽  
...  
Keyword(s):  
Cohort Study ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Reproductive Factors ◽  
Uk Biobank ◽  
Gastrointestinal Cancers ◽  
The Uk ◽  
Upper Gastrointestinal

Adolescent Police Stops, Self-Harm, and Attempted Suicide: Findings From the UK Millennium Cohort Study, 2012‒2019

2021 ◽  
pp. e1-e9
Author(s):  
Dylan B. Jackson ◽  
Alexander Testa ◽  
Rebecca L. Fix ◽  
Tamar Mendelson
Keyword(s):  
Cohort Study ◽  
United Kingdom ◽  
School Counselors ◽  
Attempted Suicide ◽  
Sociodemographic Factors ◽  
Millennium Cohort Study ◽  
The United Kingdom ◽  
Self Harm ◽  
Uk Millennium Cohort Study ◽  
The Uk

Objectives. To explore associations between police stops, self-harm, and attempted suicide among a large, representative sample of adolescents in the United Kingdom. Methods. Data were drawn from the 3 most recent sweeps of the UK Millennium Cohort Study (MCS), from 2012 to 2019. The MCS is an ongoing nationally representative contemporary birth cohort of children born in the United Kingdom between September 2000 and January 2002 (n = 10 345). Weights were used to account for sample design and multiple imputation for missing data. Results. Youths experiencing police stops by the age of 14 years (14.77%) reported significantly higher rates of self-harm (incidence rate ratio = 1.52; 95% confidence interval [CI] = 1.35, 1.69) at age 17 years and significantly higher odds of attempted suicide (odds ratio = 2.25; 95% CI = 1.84, 2.76) by age 17 years. These patterns were largely consistent across examined features of police stops and generally did not vary by sociodemographic factors. In addition, 17.73% to 40.18% of associations between police stops and outcomes were explained by mental distress. Conclusions. Police-initiated encounters are associated with youth self-harm and attempted suicide. Youths may benefit when school counselors or social workers provide mental health screenings and offer counseling care following these events. (Am J Public Health. Published online ahead of print September 23, 2021: e1–e9. https://doi.org/10.2105/AJPH.2021.306434 )

Englishness

2021 ◽  
Author(s):  
Ailsa Henderson ◽  
Richard Wyn Jones
Keyword(s):  
Public Attitudes ◽  
Political Life ◽  
British Politics ◽  
The United Kingdom ◽  
Political Implications ◽  
The World ◽  
The Uk ◽  
English Nationalism ◽  
Opinion Polls ◽  
Different Parts

For a topic that until recently was presumed not to exist, English nationalism has transformed into an apparently obvious explanation for the Brexit result in England. Subsequent opinion polls have also raised doubts about the extent of continuing English commitment to the union of the United Kingdom itself. Yet, even as Englishness is apparently reshaping Britain’s place in the world and—perhaps—the state itself, it remains poorly understood, in part because of its unfamiliarity. It has long been assumed that nationalism is a feature of political life in the state’s periphery—Scotland, Wales, and Northern Ireland—but not its English core. Another barrier to understanding bas been the relative lack of public attitudes data with which to explore the nature of English nationalist sentiment.This book draws on data from a survey vehicle—the Future of England Survey—specially established in 2011 to facilitate the exploration of patterns of national identity in England and their political implications. On the basis of these data, Englishness offers new arguments about the nature and effect of English nationalism on British politics, as well as how Britishness operates in different parts of Britain. Crucially, it demonstrates that English nationalism is emphatically not a rejection of Britain and Britishness. Rather, English nationalism combines a sense of grievance about England’s place within the UK with a fierce commitment to a particular vision of Britain’s past, present, and future. Understanding its Janus-faced nature—both England and Britain, as it were—is key not only to understanding English nationalism, but also to understanding the ways in which it is transforming British politics.

scholarly journals Homozygosity for TYK2 P1104A underlies tuberculosis in about 1% of patients in a cohort of European ancestry

2019 ◽  
Vol 116 (21) ◽  
pp. 10430-10434 ◽  
Author(s):  
Gaspard Kerner ◽  
Noe Ramirez-Alejo ◽  
Yoann Seeleuthner ◽  
Rui Yang ◽  
Masato Ogishi ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Genetic Basis ◽  
Sub Saharan Africa ◽  
European Ancestry ◽  
Uk Biobank ◽  
The United Kingdom ◽  
The Common ◽  
Sub Saharan ◽  
The Uk ◽  
High Level

The human genetic basis of tuberculosis (TB) has long remained elusive. We recently reported a high level of enrichment in homozygosity for the common TYK2 P1104A variant in a heterogeneous cohort of patients with TB from non-European countries in which TB is endemic. This variant is homozygous in ∼1/600 Europeans and ∼1/5,000 people from other countries outside East Asia and sub-Saharan Africa. We report a study of this variant in the UK Biobank cohort. The frequency of P1104A homozygotes was much higher in patients with TB (6/620, 1%) than in controls (228/114,473, 0.2%), with an odds ratio (OR) adjusted for ancestry of 5.0 [95% confidence interval (CI): 1.96–10.31, P = 2 × 10−3]. Conversely, we did not observe enrichment for P1104A heterozygosity, or for TYK2 I684S or V362F homozygosity or heterozygosity. Moreover, it is unlikely that more than 10% of controls were infected with Mycobacterium tuberculosis, as 97% were of European genetic ancestry, born between 1939 and 1970, and resided in the United Kingdom. Had all of them been infected, the OR for developing TB upon infection would be higher. These findings suggest that homozygosity for TYK2 P1104A may account for ∼1% of TB cases in Europeans.

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