Dataset Information

Genome-wide analysis of health-related biomarkers in the UK Household Longitudinal Study reveals novel associations.

ABSTRACT: Serum biomarker levels are associated with the risk of complex diseases. Here, we aimed to gain insights into the genetic architecture of biomarker traits which can reflect health status. We performed genome-wide association analyses for twenty serum biomarkers involved in organ function and reproductive health. 9,961 individuals from the UK Household Longitudinal Study were genotyped using the Illumina HumanCoreExome array and variants imputed to the 1000 Genomes Project and UK10K haplotypes. We establish a polygenic heritability for all biomarkers, confirm associations of fifty-four established loci, and identify five novel, replicating associations at genome-wide significance. A low-frequency variant, rs28929474, (beta?=?0.04, P?=?2?×?10-10) was associated with levels of alanine transaminase, an indicator of liver damage. The variant is located in the gene encoding serine protease inhibitor, low levels of which are associated with alpha-1 antitrypsin deficiency which leads to liver disease. We identified novel associations (rs78900934, beta?=?0.05, P?=?6?×?10-12; rs2911280, beta?=?0.09, P?=?6?×?10-10) for dihydroepiandrosterone sulphate, a precursor to major sex-hormones, and for glycated haemoglobin (rs12819124, beta?=?-0.03, P?=?4?×?10-9; rs761772, beta?=?0.05, P?=?5?×?10-9). rs12819124 is nominally associated with risk of type 2 diabetes. Our study offers insights into the genetic architecture of well-known and less well-studied biomarkers.

SUBMITTER: Prins BP

PROVIDER: S-EPMC5591265 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Genome-wide analysis of health-related biomarkers in the UK Household Longitudinal Study reveals novel associations.

Prins Bram P BP Kuchenbaecker Karoline B KB Bao Yanchun Y Smart Melissa M Zabaneh Delilah D Fatemifar Ghazaleh G Luan Jian'an J Wareham Nick J NJ Scott Robert A RA Perry John R B JRB Langenberg Claudia C Benzeval Michaela M Kumari Meena M Zeggini Eleftheria E

Scientific reports 20170908 1

Serum biomarker levels are associated with the risk of complex diseases. Here, we aimed to gain insights into the genetic architecture of biomarker traits which can reflect health status. We performed genome-wide association analyses for twenty serum biomarkers involved in organ function and reproductive health. 9,961 individuals from the UK Household Longitudinal Study were genotyped using the Illumina HumanCoreExome array and variants imputed to the 1000 Genomes Project and UK10K haplotypes. W ...[more]

PMID: 28887542

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Project description:ObjectivesThe association between community cultural engagement and mental health and well-being is well established. However, little is known about whether such associations are influenced by area characteristics. This study therefore examined whether the association between engagement in community cultural assets (attendance at cultural events, visiting museums and heritage sites) and subsequent well-being (life satisfaction, mental distress and mental health functioning) is moderated by neighbourhood deprivation.DesignData were drawn from Understanding Society: The UK Household Longitudinal Study waves 2 and 5. Participating households' addresses were geocoded into statistical neighbourhood zones categorised according to their level of area deprivation.SettingGeneral population.ParticipantsUK general adult population, with a total sample of 14 783.Main outcome measuresLife satisfaction was measured with a seven-point scale (1: completely unsatisfied to 7: completely satisfied). Mental distress was measured using the General Health Questionnaire 12. Mental health functioning was measured using 12-item Short Form Health Survey (SF-12).ResultsUsing Ordinary Least Squares (OLS) regression, we found that engagement in cultural assets was consistently and positively associated with subsequent life satisfaction and mental health functioning and negatively associated with mental distress. Importantly, such associations were independent of individuals' demographic background, socioeconomic characteristics and regional location. The results also show that relationships between engagement in community cultural assets and well-being were stronger in more deprived areas.ConclusionsThis study shows that engagement in community cultural assets is associated with better well-being, with some evidence that individuals in areas of high deprivation potentially may benefit more from these engagements. Given that causal mechanisms were not tested, causal claims cannot be generated from the results. However, the results suggest that place-based funding schemes that involve investment in areas of higher deprivation to improve engagement rates should be explored further to see if they can help promote better well-being among residents.

Project description:Overcrowding has been regarded as indicating material deprivation and treated as a proxy measure for individual socioeconomic status. Conventionally, 'persons per room' (PPR) has been employed to identify overcrowded households in UK survey data, though the 'bedroom standard' (BS) approach or the 'modified bedroom standard' (MBS) approach has been thought to capture overcrowded households better. Little is known about which overcrowding measure will perform well in regard to construct and face validity. In this work, associations between three overcrowding measures and socioeconomic (income and household tenure status) and health (satisfied with health and GHQ12) indicators were assessed, using the UK Household Longitudinal Study Wave 6 data. PPR, BS and MBS were derived using relevant housing grid information and housing information from the dataset, which were aggregated at a household level (N?=?18,848). Raw scores were categorised into 'under occupied (rooms?<?people)', 'balanced (rooms?=?people)', 'overcrowded (rooms?<?people)' according to an established cut-off point for each overcrowding measure. Kappa coefficient was used to assess the level of agreement between overcrowding measures. Construct validity of the measures were tested against log-transformed household equivalised income and housing tenure status as well as with each component of overcrowding measures. Using individual data (N?=?38,455), face validity of the overcrowding measures was tested against satisfaction with health and mental health indicated by GHQ12. Each overcrowding measure has a fair agreement with the others (kappa?=?0.44, p<0.001). All overcrowding measures were significantly correlated with income and household tenure in a similar manner. However, components of overcrowding measures were associated differently to these socioeconomic indicators, while they were better correlated with satisfaction with health compared to GHQ12, showing a complex aspect of overcrowding measures. In sum, use of PPR as a socioeconomic indicator is reasonable. However, given the complexity of the mechanism of health inequalities, the relevant household information is required to understand the link.

Dataset Information

Genome-wide analysis of health-related biomarkers in the UK Household Longitudinal Study reveals novel associations.

Publications

Genome-wide analysis of health-related biomarkers in the UK Household Longitudinal Study reveals novel associations.

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