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

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          Summary

          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, 2, 3]. Explanations for the association between SES and health typically focus on factors that are environmental in origin [ 4]. However, common SNPs have been found collectively to explain around 18% of the phenotypic variance of an area-based social deprivation measure of SES [ 5]. Molecular genetic studies have also shown that common physical and psychiatric diseases are partly heritable [ 6]. It is possible 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 112,151 participants of UK Biobank. We find that common SNPs explain 21% of the variation in social deprivation and 11% of household income. Two independent loci attained genome-wide significance for household income, with the most significant SNP in each of these loci being 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 SES and illnesses, anthropometric variables, psychiatric disorders, and cognitive ability. These findings suggest that some SNPs associated with SES are involved in the brain and central nervous system. The genetic associations with SES obviously do not reflect direct causal effects and are probably mediated via other partly heritable variables, including cognitive ability, personality, and health.

          Highlights

          • Common SNPs explain 21% of social deprivation and 11% of household income

          • Two loci attained genome-wide significance for household income

          • Genes in these loci have been linked to synaptic plasticity

          • Genetic correlations were found between both measures of SES and many other traits

          Abstract

          Individuals with lower socio-economic status (SES) are at increased risk of physical and mental illnesses. Hill et al. find extensive genetic correlations between SES and health, psychiatric, and cognitive traits. This suggests that the link between SES and health is driven, in part, by a shared genetic association.

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          Most cited references14

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          Intelligence and socioeconomic success: A meta-analytic review of longitudinal research

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            Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries.

            Balanced chromosomal abnormalities (BCAs) represent a relatively untapped reservoir of single-gene disruptions in neurodevelopmental disorders (NDDs). We sequenced BCAs in patients with autism or related NDDs, revealing disruption of 33 loci in four general categories: (1) genes previously associated with abnormal neurodevelopment (e.g., AUTS2, FOXP1, and CDKL5), (2) single-gene contributors to microdeletion syndromes (MBD5, SATB2, EHMT1, and SNURF-SNRPN), (3) novel risk loci (e.g., CHD8, KIRREL3, and ZNF507), and (4) genes associated with later-onset psychiatric disorders (e.g., TCF4, ZNF804A, PDE10A, GRIN2B, and ANK3). We also discovered among neurodevelopmental cases a profoundly increased burden of copy-number variants from these 33 loci and a significant enrichment of polygenic risk alleles from genome-wide association studies of autism and schizophrenia. Our findings suggest a polygenic risk model of autism and reveal that some neurodevelopmental genes are sensitive to perturbation by multiple mutational mechanisms, leading to variable phenotypic outcomes that manifest at different life stages. Copyright © 2012 Elsevier Inc. All rights reserved.
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              Health inequalities among British civil servants: the Whitehall II study.

              The Whitehall study of British civil servants begun in 1967, showed a steep inverse association between social class, as assessed by grade of employment, and mortality from a wide range of diseases. Between 1985 and 1988 we investigated the degree and causes of the social gradient in morbidity in a new cohort of 10,314 civil servants (6900 men, 3414 women) aged 35-55 (the Whitehall II study). Participants were asked to answer a self-administered questionnaire and attend a screening examination. In the 20 years separating the two studies there has been no diminution in social class difference in morbidity: we found an inverse association between employment grade and prevalence of angina, electrocardiogram evidence of ischaemia, and symptoms of chronic bronchitis. Self-perceived health status and symptoms were worse in subjects in lower status jobs. There were clear employment-grade differences in health-risk behaviours including smoking, diet, and exercise, in economic circumstances, in possible effects of early-life environment as reflected by height, in social circumstances at work (eg, monotonous work characterised by low control and low satisfaction), and in social supports. Healthy behaviours should be encouraged across the whole of society; more attention should be paid to the social environments, job design, and the consequences of income inequality.
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                Author and article information

                Contributors
                Journal
                Curr Biol
                Curr. Biol
                Current Biology
                Cell Press
                0960-9822
                1879-0445
                21 November 2016
                21 November 2016
                : 26
                : 22
                : 3083-3089
                Affiliations
                [1 ]Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK
                [2 ]Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK
                [3 ]Division of Psychiatry, University of Edinburgh, Morningside Terrace, Edinburgh EH10 5HF, UK
                [4 ]Medical Genetics Section, University of Edinburgh Centre for Genomics and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
                [5 ]Queensland Brain Institute, The University of Queensland, St Lucia, Queensland 4072, Australia
                [6 ]Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, Burgemeester Oudlaan 50, Rotterdam 3062 PA, the Netherlands
                [7 ]Department of Epidemiology, Erasmus Medical Center, Gravendijkwal 230, Rotterdam 3015 GE, the Netherlands
                [8 ]Erasmus University Rotterdam Institute for Behavior and Biology, Gravendijkwal 230, Rotterdam 3062 PA, the Netherlands
                [9 ]MRC Lifecourse Epidemiology Unit, University of Southampton, Tremona Rd, Southampton SO16 6YD, UK
                Author notes
                []Corresponding author david.hill@ 123456ed.ac.uk
                [∗∗ ]Corresponding author ian.deary@ 123456ed.ac.uk
                [10]

                Co-first author

                [11]

                Lead Contact

                Article
                S0960-9822(16)31119-8
                10.1016/j.cub.2016.09.035
                5130721
                27818178
                d79242cb-c2f6-44a4-bb9c-ba9c91185515
                © 2016 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 1 March 2016
                : 13 July 2016
                : 19 September 2016
                Categories
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                Life sciences
                gwas,genetics,genetic correlation,uk biobank,socioeconomic status,ses,income,social deprivation
                Life sciences
                gwas, genetics, genetic correlation, uk biobank, socioeconomic status, ses, income, social deprivation

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