scholarly journals Molecular Genetic Contributions to Social Deprivation and Household Income in UK Biobank

2016 ◽  
Vol 26 (22) ◽  
pp. 3083-3089 ◽  
Author(s):  
W. David Hill ◽  
Saskia P. Hagenaars ◽  
Riccardo E. Marioni ◽  
Sarah E. Harris ◽  
David C.M. Liewald ◽  
...  
2016 ◽  
Author(s):  
William David Hill ◽  
Saskia P Hagenaars ◽  
Riccardo E Marioni ◽  
Sarah E Harris ◽  
David CM Liewald ◽  
...  

Individuals with lower socio-economic status (SES) are at increased risk of physical and mental illnesses and tend to die at an earlier age [1-3]. Explanations for the association between SES and health typically focus on factors that are environmental in origin [4]. However, common single nucleotide polymorphisms (SNPs) have been found collectively to explain around 18% (SE = 5%) of the phenotypic variance of an area-based social deprivation measure of SES [5]. Molecular genetic studies have also shown that physical and psychiatric diseases are at least partly heritable [6]. It is possible, therefore, that phenotypic associations between SES and health arise partly due to a shared genetic etiology. We conducted a genome-wide association study (GWAS) on social deprivation and on household income using the 112,151 participants of UK Biobank. We find that common SNPs explain 21% (SE = 0.5%) of the variation in social deprivation and 11% (SE = 0.7%) in household income. Two independent SNPs attained genome-wide significance for household income, rs187848990 on chromosome 2, and rs8100891 on chromosome 19. Genes in the regions of these SNPs have been associated with intellectual disabilities, schizophrenia, and synaptic plasticity. Extensive genetic correlations were found between both measures of socioeconomic status and illnesses, anthropometric variables, psychiatric disorders, and cognitive ability. These findings show that some SNPs associated with SES are involved in the brain and central nervous system. The genetic associations with SES are probably mediated via other partly-heritable variables, including cognitive ability, education, personality, and health.


2021 ◽  
Vol 10 (9) ◽  
pp. 1880
Author(s):  
Paola Galozzi ◽  
Sara Bindoli ◽  
Andrea Doria ◽  
Francesca Oliviero ◽  
Paolo Sfriso

In the panorama of inflammatory arthritis, gout is the most common and studied disease. It is known that hyperuricemia and monosodium urate (MSU) crystal-induced inflammation provoke crystal deposits in joints. However, since hyperuricemia alone is not sufficient to develop gout, molecular-genetic contributions are necessary to better clinically frame the disease. Herein, we review the autoinflammatory features of gout, from clinical challenges and differential diagnosis, to the autoinflammatory mechanisms, providing also emerging therapeutic options available for targeting the main inflammatory pathways involved in gout pathogenesis. This has important implication as treating the autoinflammatory aspects and not only the dysmetabolic side of gout may provide an effective and safer alternative for patients even in the prevention of possible gouty attacks.


Intelligence ◽  
2014 ◽  
Vol 44 ◽  
pp. 26-32 ◽  
Author(s):  
Riccardo E. Marioni ◽  
Gail Davies ◽  
Caroline Hayward ◽  
Dave Liewald ◽  
Shona M. Kerr ◽  
...  

2021 ◽  
Author(s):  
David Curtis

AbstractBackgroundDepression is moderately heritable but there is no common genetic variant which has a major effect on susceptibility. A previous analysis of 50,000 subjects failed to implicate any genes or sets of genes associated with risk of affective disorder requiring specialist treatment. A large exome-sequenced dataset is now available.MethodsData from 200,632 exome-sequenced UK Biobank participants was analysed. Subjects were treated as cases if they had reported having seen a psychiatrist for “nerves, anxiety, tension or depression”. Gene-wise weighted burden analysis was performed to see if there were any genes or sets of genes for which there was an excess of rare, functional variants in cases.ResultsThere were 22,886 cases and 176,486 controls. There were 22,642 informative genes but no gene or gene set produced a statistically significant result after correction for multiple testing. None of the genes or gene sets with the lowest p values appeared to be a biologically plausible candidate.LimitationsThe phenotype is based on self-report and the cases are likely to somewhat heterogeneous. Likewise, it is expected that some of the subjects classed as controls will in fact have suffered from depression or some other psychiatric diagnosis.ConclusionsThe results conform exactly with the expectation under the null hypothesis. It seems unlikely that the use of common, poorly defined phenotypes will produce useful advances in understanding genetic contributions to affective disorder and it might be preferable to focus instead on obtaining large exome-sequenced samples of conditions such as bipolar 1 disorder and severe, recurrent depression.


2019 ◽  
Vol 14 (5) ◽  
pp. 1468-1476 ◽  
Author(s):  
Donald M. Lyall ◽  
Simon R. Cox ◽  
Laura M. Lyall ◽  
Carlos Celis-Morales ◽  
Breda Cullen ◽  
...  

Abstract Apolipoprotein (APOE) e4 genotype is an accepted risk factor for accelerated cognitive aging and dementia, though its neurostructural substrates are unclear. The deleterious effects of this genotype on brain structure may increase in magnitude into older age. This study aimed to investigate in UK Biobank the association between APOE e4 allele presence vs. absence and brain imaging variables that have been associated with worse cognitive abilities; and whether this association varies by cross-sectional age. We used brain magnetic resonance imaging (MRI) and genetic data from a general-population cohort: the UK Biobank (N = 8395 after exclusions). We adjusted for the covariates of age in years, sex, Townsend social deprivation scores, smoking history and cardiometabolic diseases. There was a statistically significant association between APOE e4 genotype and increased (i.e. worse) white matter (WM) hyperintensity volumes (standardised beta = 0.088, 95% confidence intervals = 0.036 to 0.139, P = 0.001), a marker of poorer cerebrovascular health. There were no associations with left or right hippocampal, total grey matter (GM) or WM volumes, or WM tract integrity indexed by fractional anisotropy (FA) and mean diffusivity (MD). There were no statistically significant interactions with age. Future research in UK Biobank utilising intermediate phenotypes and longitudinal imaging hold significant promise for this area, particularly pertaining to APOE e4’s potential link with cerebrovascular contributions to cognitive aging.


Author(s):  
Aniruddh P. Patel ◽  
Manish D. Paranjpe ◽  
Nina P. Kathiresan ◽  
Manuel A. Rivas ◽  
Amit V. Khera

Preliminary reports suggest that the Coronavirus Disease 2019 (COVIDâ^’19) pandemic has led to disproportionate morbidity and mortality among historically disadvantaged populations. The extent to which these disparities are related to socioeconomic versus biologic factors is largely unknown. We investigate the racial and socioeconomic associations of COVIDâ^’19 hospitalization among 418,794 participants of the UK Biobank, of whom 549 (0.13%) had been hospitalized. Both black participants (odds ratio 3.4; 95%CI 2.4â^’4.9) and Asian participants (odds ratio 2.1; 95%CI 1.5â^’3.2) were at substantially increased risk as compared to white participants. We further observed a striking gradient in COVIDâ^’19 hospitalization rates according to the Townsend Deprivation Index â^’ a composite measure of socioeconomic deprivation â^’ and household income. Adjusting for such factors led to only modest attenuation of the increased risk in black participants, adjusted odds ratio 3.1 (95%CI 2.0â^’4.8). These observations confirm and extend earlier preliminary and lay press reports of higher morbidity in non-white individuals in the context of a large population of participants in a national biobank. The extent to which this increased risk relates to variation in pre-existing comorbidities, differences in testing or hospitalization patterns, or additional disparities in social determinants of health warrants further study.


Author(s):  
Ted Reichborn-Kjennerud ◽  
Kenneth S. Kendler

This chapter reviews the evidence for genetic contributions to the etiology of personality disorders (PDs) as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM; 5th ed.). This approach and some of the controversial issues associated with its development are briefly described in the first section. The second section evaluates the evidence for genetic influence on DSM PDs from family and twin studies using quantitative genetic methods. Studies that move beyond individual PDs are also reviewed, together with studies on the extent to which common genetic factors influence PDs and normal personality traits and PDs and pathological personality trait domains. Stability of genetic influences on PDs over time are also examined. Molecular genetic studies are reviewed in the third section. The fourth section deals with gene environment interplay, and the final section discusses future directions in the exploration of genetic influences on PDs.


2019 ◽  
Vol 50 (15) ◽  
pp. 2526-2535 ◽  
Author(s):  
Mark J. Adams ◽  
David M. Howard ◽  
Michelle Luciano ◽  
Toni-Kim Clarke ◽  
Gail Davies ◽  
...  

AbstractBackgroundMajor depressive disorder and neuroticism (Neu) share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression.MethodsWe analysed summary statistics from genome-wide association studies (GWAS) of depression (from the Psychiatric Genomics Consortium, 23andMe and UK Biobank) and compared them with GWAS of Neu (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only Neu or with both. Second, we estimated partial genetic correlations to test whether the depression's genetic link with other phenotypes was explained by shared overlap with Neu.ResultsWe found evidence that most genomic regions (25/37) associated with depression are likely to be shared with Neu. The overlapping common genetic variance of depression and Neu was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that were not shared with Neu, were positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with Neu, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease and age of first birth. Independent of depression, Neu had specific genetic correlates in ulcerative colitis, pubertal growth, anorexia and education.ConclusionOur findings demonstrate that, while genetic risk factors for depression are largely shared with Neu, there are also non-Neu-related features of depression that may be useful for further patient or phenotypic stratification.


2019 ◽  
Author(s):  
Sean Harrison ◽  
Alisha R Davies ◽  
Matt Dickson ◽  
Jessica Tyrrell ◽  
Michael J Green ◽  
...  

AbstractObjectivesTo estimate the causal effect of health conditions and risk factors on social and socioeconomic outcomes in UK Biobank. Evidence on socioeconomic impacts is important to understand because it can help governments, policy-makers and decision-makers allocate resources efficiently and effectively.DesignWe used Mendelian randomization to estimate the causal effects of eight health conditions (asthma, breast cancer, coronary heart disease, depression, eczema, migraine, osteoarthritis, type 2 diabetes) and five health risk factors (alcohol intake, body mass index [BMI], cholesterol, systolic blood pressure, smoking) on 19 social and socioeconomic outcomes.SettingUK Biobank.Participants337,009 men and women of white British ancestry, aged between 39 and 72 years.Main outcome measuresAnnual household income, employment, deprivation (measured by the Townsend deprivation index [TDI]), degree level education, happiness, loneliness, and 13 other social and socioeconomic outcomes.ResultsResults suggested that BMI, smoking and alcohol intake affect many socioeconomic outcomes. For example, smoking was estimated to reduce household income (mean difference = −£24,394, 95% confidence interval (CI): −£33,403 to −£15,384), the chance of owning accommodation (absolute percentage change [APC] = −21.5%, 95% CI: −29.3% to −13.6%), being satisfied with health (APC = −32.4%, 95% CI: −48.9% to −15.8%), and of obtaining a university degree (APC = −73.8%, 95% CI: −90.7% to −56.9%), while also increasing deprivation (mean difference in TDI = 1.89, 95% CI: 1.13 to 2.64, approximately 236% of a decile of TDI). There was evidence that asthma increased deprivation and decreased both household income and the chance of obtaining a university degree, and migraine reduced the chance of having a weekly leisure or social activity, especially in men. For other associations, estimates were null.ConclusionsHigher BMI, alcohol intake and smoking were all estimated to adversely affect multiple social and socioeconomic outcomes. Effects were not detected between health conditions and socioeconomic outcomes using Mendelian randomization, with the exceptions of depression, asthma and migraines. This may reflect true null associations, selection bias given the relative health and age of participants in UK Biobank, and/or lack of power to detect effects.What is known?Studies have shown associations between poor health and adverse social (e.g. wellbeing, social contact) and socioeconomic (e.g. educational attainment, income, employment) outcomes, but there is also strong evidence that social and socioeconomic factors influence health.These bidirectional relationships make it difficult to establish whether health conditions and health risk factors have causal effects on social and socioeconomic outcomes.Mendelian randomization is a technique that uses genetic variants robustly related to an exposure of interest (here, health conditions and risk factors for poor health) as a proxy for the exposure.Since genetic variants are randomly allocated at conception, they tend to be unrelated to the factors that typically confound observational studies, and are less likely to suffer from reverse causality, making causal inference from Mendelian randomization analyses more plausible.What this study addsThis study suggests causal effects of higher BMI, smoking and alcohol use on a range of social and socioeconomic outcomes, implying that population-level improvements in these risk factors may, in addition to the well-known health benefits, have social and socioeconomic benefits for individuals and society.There was evidence that asthma increased deprivation, decreased household income and the chance of having a university degree, migraine reduced the chance of having a weekly leisure or social activity, especially in men, and depression increased loneliness and decreased happiness.There was little evidence for causal effects of cholesterol, systolic blood pressure or breast cancer on social and socioeconomic outcomes.


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