Meena Kumari

• Ph.D.
• Professor at University of Essex

Poor mental health constitutes a public health crisis due to its high prevalence, unmet need and its mechanistic heterogeneity. A comprehensive understanding of the biological correlates of poor mental health in the population could enhance epidemiological research and eventually help guide treatment strategies. The human bloodstream contains many...

Interindividual genetic variability is well characterised, but we still lack a complete catalogue of loci displaying variable and stable epigenetic patterns. Here, we report a catalogue of stable and variable interindividual DNA methylation in human whole blood by analysing the DNA methylation patterns in 3642 individuals using the IlluminaEPIC arr...

Although a significant body of research has shown that married people are healthier and live longer, empirical research on sex differences in the link between marital status and health suggests results are mixed. Moreover, the sex disparities in marital status and health relationships vary across adulthood. The literature on partnership status and...

Background Ketone bodies (KBs) are an alternative energy supply for brain functions when glucose is limited. The most abundant ketone metabolite, 3-β-hydroxybutyrate (BOHBUT), has been suggested to prevent or delay cognitive impairment, but the evidence remains unclear. We triangulated observational and Mendelian randomization (MR) studies to inves...

Dried blood spot (DBS) sample collection has been suggested as a less invasive, cheaper and more convenient alternative to venepuncture, which requires trained personnel, making it a potentially viable approach for self-collection of blood on a large scale. We examine whether participants in a longitudinal survey were willing to provide a DBS sampl...

Background: While medical studies generally provide health feedback to participants, in observational studies this is not always the case due to logistical and financial difficulties, or concerns about changing observed behaviours. However, evidence suggests that lack of feedback may deter participants from providing biological samples. This paper...

Non-technical summary: Due to recent developments in laboratory methods, large numbers of proteins which are present in the blood at low concentrations can now be measured simultaneously, a technology called "proteomics". When these proteins are measured in studies of the general population, they may provide useful insights into how social factors...

Background Dried blood spot (DBS) sample collection has been suggested as a less invasive, cheaper and more convenient alternative to venepuncture, which requires trained personnel, making it a potentially viable approach for self-collection of blood on a large scale. We examine whether participants in a longitudinal survey were willing to provide...

A user guide for the Understanding Society proteomics dataset

Disadvantaged socio-economic position (SEP) is associated with greater biological age, relative to chronological age, measured by DNA methylation (positive ‘age acceleration’, AA). Social mobility has been proposed to ameliorate health inequalities. This study aimed to understand the association of social mobility with positive AA. Diagonal referen...

Most epigenetic epidemiology to date has utilized microarrays to identify positions in the genome where variation in DNA methylation is associated with environmental exposures or disease. However, these profile less than 3% of DNA methylation sites in the human genome, potentially missing affected loci and preventing the discovery of disrupted biol...

Background Sex differences are known to play a role in disease aetiology, progression and outcome. Previous studies have revealed autosomal epigenetic differences between males and females in some tissues, including differences in DNA methylation patterns. Here, we report for the first time an analysis of autosomal sex differences in DNAme using th...

Most epigenetic epidemiology to date has utilized microarrays to identify positions in the genome where variation in DNA methylation is associated with environmental exposures or disease. However, these profile less than 3% of DNA methylation sites in the human genome, potentially missing affected loci and preventing the discovery of disrupted biol...

Variation in DNA methylation (DNAm) is associated with multiple biological processes that track growth and development, ageing and age-related diseases. However, there is little understanding of what constitutes typical patterns of DNAm variation and how these patterns change across the life course. In this study, we synthesised a map of the human...

Sex differences are known to play a role in disease etiology, progression and outcome. Previous studies have revealed autosomal epigenetic differences between males and females in some tissues, including differences in DNA methylation patterns. Here, we report for the first time an analysis of autosomal sex differences in DNAme using the Illumina E...

Background The positive direct relation between stress and the development of cardiovascular disease has increasingly been recognized. However, the link between hypothalamic-pituitary-adrenal (HPA) dysregulation and subclinical cardiovascular disease has not been studied longitudinally. We investigated the relation of diurnal salivary cortisol, as...

Context Multiple observational studies have reported an inverse relationship between 25-hydroxyvitamin D concentrations (25(OH)D) and type 2 diabetes (T2D). However, the results of short- and long-term interventional trials concerning the relationship between 25(OH)D and T2D risk have been inconsistent. Objectives and methods To evaluate the causa...

Background Sex is an important covariate of epigenome-wide association studies due to its strong influence on DNA methylation patterns across numerous genomic positions. Nevertheless, many samples on the Gene Expression Omnibus (GEO) frequently lack a sex annotation or are incorrectly labelled. Considering the influence that sex imposes on DNA meth...

Background: Genome-wide association studies (GWAS) have not identified replicable genetic risk loci for stress or urgency urinary incontinence. Methods: We carried out a discovery stage case control GWAS in three independent discovery cohorts of European women (n=8,979) for stress incontinence, urgency incontinence, and any incontinence phenotyp...

A Correction to this paper has been published: https://doi.org/10.1038/s41366-021-00770-0

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21276-3

Interleukin-6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery, and replication meta genome-wide association study (G...

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women...

Human DNA methylation data have been used to develop biomarkers of ageing, referred to as ‘epigenetic clocks’, which have been widely used to identify differences between chronological age and biological age in health and disease including neurodegeneration, dementia and other brain phenotypes. Existing DNA methylation clocks have been shown to be...

Sex is an important covariate of epigenome-wide association studies due to its strong influence on DNA methylation patterns across numerous genomic positions. Nevertheless, many samples on the Gene Expression Omnibus (GEO) frequently lack a sex annotation or are incorrectly labelled. Considering the influence that sex imposes on DNA methylation pat...

Background: Nuclear magnetic resonance (NMR) allows triglycerides (TG) to be subclassified into 14 different classes based on particle size and lipid content. We recently showed that these sub-fractions have differential associations with cardiovascular disease (CVD) events. We report the distributions and define reference interval ranges for 14 T...

Human DNA-methylation data have been used to develop biomarkers of ageing - referred to epigenetic clocks - that have been widely used to identify differences between chronological age and biological age in health and disease including neurodegeneration, dementia and other brain phenotypes. Existing DNA methylation clocks are highly accurate in blo...

Importance: Cholesterol content in high-density lipoprotein particles (HDL-C) is associated inversely with coronary heart disease (CHD), but findings from Mendelian randomization studies and randomized trials of HDL-C raising drugs have questioned whether this link is causal. However, these analyses do not exclude a causal role for specific HDL sub...

Background We aimed at investigating the association of circulating fatty acids with coronary heart disease ( CHD ) and stroke risk. Methods and Results We conducted an individual‐participant data meta‐analysis of 5 UK ‐based cohorts and 1 matched case‐control study. Fatty acids (ie, omega‐3 docosahexaenoic acid, omega‐6 linoleic acid, monounsatur...

Aims Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease; however, there is uncertainty about the role of total triglycerides and the individual triglyceride-containing lipoprotein sub-fractions. We measured 14 triglyceride-containing lipoprotein sub-fractions using nuclear magnetic resonance and examine...

Background: The Horvath epigenetic clock is widely used. It predicts age quite well from 353 CpG sites in the DNA methylation profile in unknown samples and has been used to calculate "age acceleration" in various tissues and environments. Results: The model systematically underestimates age in tissues from older people. This is seen in all exam...

Sleep is an essential human function but its regulation is poorly understood. Using accelerometer data from 85,670 UK Biobank participants, we perform a genome-wide association study of 8 derived sleep traits representing sleep quality, quantity and timing, and validate our findings in 5,819 individuals. We identify 47 genetic associations at P < 5...

Abstract Background There has been a steady increase in the number of studies aiming to identify DNA methylation differences associated with complex phenotypes. Many of the challenges of epigenetic epidemiology regarding study design and interpretation have been discussed in detail, however there are analytical concerns that are outstanding and req...

SIM_8066‐Supp‐0001‐Multiple_SNPs_Draft_StatMed_Revision_supplementary.docx

In high-income countries there is an established link between high body mass index (BMI) and low income, but the direction of this association is unclear. Recent analyses in a large UK population using genetically-instrumented BMI supported a causal influence of BMI on household income, educational attainment and job class. Since analyses were base...

Evidence on the association between functioning of the hypothalamic pituitary adrenal (HPA) axis and cognitive capability at older ages is mixed. We undertook a systematic review (until October 2016) and individual participant data (IPD) meta-analysis to test if dysregulation of the HPA axis is associated with worse cognitive capability. Five cohor...

We introduce two novel methods for multivariate genome-wide-association meta-analysis (GWAMA) of related traits that correct for sample overlap. A broad range of simulation scenarios supports the added value of our multivariate methods relative to univariate GWAMA. We applied the novel methods to life satisfaction, positive affect, neuroticism, and...

Humans vary substantially in their willingness to take risks. In a combined sample of over one million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. We identified 611 approximately independent genetic loci associ...

Humans vary substantially in their willingness to take risks. In a combined sample of over one million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. We identified 611 approximately independent genetic loci associ...

Background Success in the identification of genetic variants associated with neuropsychiatric disorders is one of the major achievements in contemporary biomedical research. Most genetic variants identified in Genome-Wide Association Studies (GWAS) of complex traits are thought to act via effects on gene regulation rather than directly altering the...

The “some invalid, some valid instrumental variable estimator” (sisVIVE) is a lasso‐based method for instrumental variables (IVs) regression of outcome on an exposure. In principle, sisVIVE is robust to some of the IVs in the analysis being invalid, in the sense of being related to the outcome variable through pathways not mediated by the exposure....

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight n...

Observational studies find an association between increased body mass index (BMI) and short self‐reported sleep duration in adults. However, the underlying biological mechanisms that underpin these associations are unclear. Recent findings from the UK Biobank suggest a weak genetic correlation between BMI and self‐reported sleep duration. However,...

Observational studies find an association between increased body mass index (BMI) and short self‐reported sleep duration in adults. However, the underlying biological mechanisms that underpin these associations are unclear. Recent findings from the UK Biobank suggest a weak genetic correlation between BMI and self‐reported sleep duration. However,...

Background: To date, little attention has been paid to supportive relationships as factors contributing to weight loss from bariatric surgery. Material and methods: This prospective study examined whether total percentage weight loss (%TWL) at 3, 12 and 24 months post-surgery varies by distinct aspects of pre-surgery social support (received emo...

Background Although social networks’ influence on obesity has been increasingly recognised, it remains unclear if different dimensions of social support, for example, emotional or practical support, received from one’s closest relationship are associated with weight outcomes over mid-life and old age. Methods Using linear mixed models we examined...

Characterizing the complex relationship between genetic, epigenetic, and transcriptomic variation has the potential to increase understanding about the mechanisms underpinning health and disease phenotypes. We undertook a comprehensive analysis of common genetic variation on DNA methylation (DNAm) by using the Illumina EPIC array to profile samples...

Sleep is an essential human function but its regulation is poorly understood. Identifying genetic variants associated with quality, quantity and timing of sleep will provide biological insights into the regulation of sleep and potential links with disease. Using accelerometer data from 85,670 individuals in the UK Biobank, we performed a genome-wid...

Background: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report de...

The objective was to investigate the relationship between various aspects of informal caregiving and diurnal patterns of salivary cortisol, with special attention to the moderating effect of sex and work status. The study population was composed of 3727 men and women from the British Whitehall II study. Salivary cortisol was measured six times duri...

Background Shift work is a feature of many occupations and has been associated with a range of adverse health outcomes, including obesity, diabetes, depression and cancer. The main proposed mechanism linking them is a disruption in circadian rhythms, particularly among night shift workers. DNA methylation may serve as a biomarker for circadian disr...

Motivation The datasets generated by DNA methylation analyses are getting bigger. With the release of the HumanMethylationEPIC micro-array and datasets containing thousands of samples, analyses of these large datasets using R are becoming impractical due to large memory requirements. As a result there is an increasing need for computationally effic...

Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development p...

Accelerated DNA methylation age is linked to all-cause mortality and environmental factors, but studies of associations with socioeconomic position are limited. Studies generally use small selected samples, and it is unclear how findings with two commonly used methylation age calculations (Horvath and Hannum) translate to general population samples...

Background: The methylation status of numerous CpG sites in the human genome varies with age. The Horvath epigenetic clock used a wide variety of published DNA methylation data to produce an age prediction that has been widely used to, predict age in unknown samples, and draw conclusions about speed of ageing in various tissues, environments, and d...

Background: Genomic and biosocial research data about individuals is rapidly proliferating, bringing the potential for novel opportunities for data integration and use. The scale, pace and novelty of these applications raise a number of urgent sociotechnical, ethical and legal questions, including optimal methods of data storage, management and ac...

Characterizing the complex relationship between genetic, epigenetic and transcriptomic variation has the potential to increase understanding about the mechanisms underpinning health and disease phenotypes. In this study, we describe the most comprehensive analysis of common genetic variation on DNA methylation (DNAm) to date, using the Illumina EPI...

BACKGROUND: Adiponectin, a circulating adipocyte-derived protein, has insulin-sensitizing, anti-inflammatory, antiatherogenic, and cardiomyocyte-protective properties in animal models. However, the systemic effects of adiponectin in humans are unknown. Our aims were to define the metabolic profile associated with higher blood adiponectin concentrat...

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 Househ...

Background: Adiponectin, a circulating adipocyte-derived protein, has insulin-sensitizing, anti-inflammatory, antiatherogenic, and cardiomyocyte-protective properties in animal models. However, the systemic effects of adiponectin in humans are unknown. Our aims were to define the metabolic profile associated with higher blood adiponectin concentra...

Observational studies find an association between body mass index (BMI) and self-reported sleep duration in adults such that a higher BMI is associated with shorter duration of sleep. However, the key question here is whether this relationship is causal, in either direction. Recently, findings from a Mendelian randomisation study in the UK Biobank...

The causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their...

Background Systemic inflammation may play a role in the development of idiopathic fatigue, that is, fatigue not explained by infections or diagnosed chronic illness, but this relationship has never been investigated in community studies including the entire adult age span. We examine the association of the inflammatory marker C-reactive protein (CR...

Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated wi...

Cohort information, genotyping, quality control (QC), glycated hemoglobin (HbA1c), analysis and covariates. (XLSX)

Genome-wide significant SNPs identified in the genetic discovery analysis. (XLSX)

Proportion of additional variance explained over age and sex in measured glycated hemoglobin (HbA1c) by erythryocytic genetic variants and by all genome-wide significant genetic variants by ethnicity. (XLSX)

Mean difference in glycated hemoglobin (HbA1c) between the top and bottom 5 percentile of genetic score-total (GS-Total) by ancestry. (XLSX)

Additional analyses on the association of rs1050828, G6PD variant G202A, with glycated hemoglobin (HbA1c). (XLSX)

Association of lead glycated hemoglobin (HbA1c) variants with glycemic and erythrocytic traits from publicly available association results. (XLSX)