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Anbupalam Thalamuthu

Anbupalam Thalamuthu

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306
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Introduction

Publications

Publications (306)
Article
Full-text available
Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1,...
Article
Full-text available
Healthy metabolic measures in humans are associated with longevity. Dysregulation leads to metabolic syndrome (MetS) and negative health outcomes. Recent exceptional longevity (EL) genome wide association studies have facilitated estimation of an individual’s polygenic risk score (PRS) for EL. We tested the hypothesis that individuals with high ELP...
Article
Full-text available
Polygenic risk scores (PRSs) can boost risk prediction in late-onset Alzheimer’s disease (LOAD) beyond apolipoprotein E (APOE) but have not been leveraged to identify genetic resilience factors. Here, we sought to identify resilience-conferring common genetic variants in (1) unaffected individuals having high PRSs for LOAD, and (2) unaffected APOE-...
Article
Objectives Prior work suggests that higher fruit and vegetable consumption may protect against depression in older adults. By better understanding the influence of genetic and environmental factors on fruit and vegetable intakes, more effective interventions could be designed to increase intakes in older adults to reduce and/or assist with the trea...
Preprint
Polygenic risk scores (PRSs) can boost risk-prediction in late-onset Alzheimer’s disease (LOAD) beyond apolipoprotein E ( APOE) but have not been leveraged to identify genetic resilience factors. Here, we sought to identify resilience-conferring common genetic variants in 1) unaffected individuals having high PRSs for LOAD, and 2) unaffected APOE -...
Article
Full-text available
Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association...
Article
Full-text available
Background Previous findings for the genetic and environmental contributions to DNA methylation variation were for limited age ranges only. We investigated the lifespan contributions and their implications for human health for the first time. Methods 1,720 monozygotic twin (MZ) pairs and 1,107 dizygotic twin (DZ) pairs aged 0-92 years were include...
Article
Background Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment. Aims To use a combination of transdiagnostic genetic and clinical factors to predict l...
Article
Full-text available
Major Depressive Disorder (MDD) often is associated with significant cognitive dysfunction. We conducted a meta-analysis of genome-wide interaction of MDD and cognitive function using data from four large European cohorts in a total of 3510 MDD cases and 6057 controls. In addition, we conducted analyses using polygenic risk scores (PRS) based on da...
Article
Objective To determine the proportional genetic contribution to the variability of cerebral β-amyloid load in older adults using the classic twin design. Methods Participants (n=206) comprising 61 monozygotic (MZ) twin pairs (68 (55.74%) females; mean age (SD): 71.98 (6.43) years), and 42 dizygotic (DZ) twin pairs (56 (66.67%) females; mean age: 7...
Article
Full-text available
Age and sex associated with changes in the functional brain network topology and cognition in large population of older adults have been poorly understood. We explored this question further by examining differences in 11 resting-state graph theory measures with respect to age, sex, and their relationships with cognitive performance in 17,127 United...
Article
Full-text available
Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molec...
Article
Human longevity is moderately heritable and is hence influenced by both genetic and environmental factors. However, there remains considerable uncertainty regarding its relationship with brain ageing. Here, we used a discovery sample (N=19136, aged 45-81 years) from the UK Biobank and a replication sample (N=809, aged 66-93 years) from the Sydney M...
Preprint
Perivascular space burden (PVS) is an emerging and possibly the earliest magnetic resonance imaging (MRI)-marker of cerebral small vessel disease (cSVD), a leading cause of stroke and dementia. Its molecular underpinnings are unknown. Genome-wide and whole-exome association studies in 40,095 participants (21 population-based cohorts, 66.3±8.6 years...
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Full-text available
Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI (n = 6420) and genetic data (n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI > 30) was significantly associated with cortical an...
Article
Full-text available
DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neur...
Preprint
BACKGROUND Age and sex associated with changes in functional brain network topology and cognition in large population of older adults have been poorly understood. We explored this question further by examining differences in 11 resting-state graph theory measures with respect to age, sex, and their relationships with cognitive performance in 17,127...
Article
Full-text available
Here, we investigated the genetics of weighted functional brain network graph theory measures from 18,445 participants of the UK Biobank (44–80 years). The eighteen measures studied showed low heritability (mean h2SNP = 0.12) and were highly genetically correlated. One genome-wide significant locus was associated with strength of somatomotor and li...
Article
Diffusion weighted imaging (DWI) is a widely recognized neuroimaging technique to evaluate the microstructure of brain white matter. The objective of this study is to establish an improved automated DWI marker for estimating white matter integrity and investigating ageing related cognitive decline. The concept of Wasserstein distance was introduced...
Article
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Lipidomics research could provide insights of pathobiological mechanisms in Alzheimer’s disease. This study explores a battery of plasma lipids that can differentiate Alzheimer’s disease (AD) patients from healthy controls and determines whether lipid profiles correlate with genetic risk for AD. AD plasma samples were collected from the Sydney Memo...
Article
Full-text available
Ageing is associated with a decrease in odour identification. Additionally, deficits in olfaction have been linked to age-related disease and mortality. Heritability studies suggest genetic variation contributes to olfactory identification. The olfactory receptor (OR) gene family is the largest in the human genome and responsible for overall odour...
Article
Empathy is essential for navigating complex social environments. Prior work has shown associations between rs53576, a single nucleotide polymorphism (SNP) located in the oxytocin receptor gene (OXTR), and generalized empathy. We undertook a systematic review and meta-analysis to assess the effects of rs53576 on subdomains of empathy, specifically c...
Article
Full-text available
Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain st...
Preprint
Human longevity is moderately heritable and is hence influenced by both genetic and environmental factors. However, there remains considerable uncertainty regarding its relationship with brain ageing. In this study, we investigated the associations of parental lifespan (parental age at death) and polygenic risk score for longevity (longevity-PRS) w...
Article
Full-text available
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...
Preprint
Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain str...
Article
Full-text available
Background DNA methylation-based biological age (DNAm age) is an important biomarker for adult health. Studies in specific age ranges have found widely varying results about its genetic and environmental causes of variation. However, these studies are not able to provide a comprehensive view of the causes of variation over the lifespan. Results In...
Article
Neuroinflammation, synaptic function, and neurotransmission are implicated in gene expression studies of human brain aging. We examined 869 genes specific to these 3 pathways using RNA sequencing in 2 age‐critical brain regions of the human brain, the dorsolateral prefrontal cortex (DLPFC) and posterior cingulate cortex (PCC) in a post‐mortem cohor...
Article
Full-text available
White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were...
Article
Hippocampal volume is an important biomarker of Alzheimer's disease (AD), and genetic risk of AD is associated with hippocampal atrophy. However, the hippocampus is not a uniform structure and has a number of subfields, the associations of which with age, sex, and polygenic risk score for AD (PRS AD) have been inadequately investigated. We examined...
Preprint
Full-text available
Hippocampal volume is an important biomarker of Alzheimer's disease (AD), and genetic risk of AD is associated with hippocampal atrophy. However, the hippocampus is not a uniform structure and has a number of subfields, the associations of which with age, sex, and polygenic risk score for AD (PRSAD) have been inadequately investigated. We examined...
Article
Background While midlife hypertension is deleterious, late-life hypertension has been associated with better cognitive outcomes in several studies. Many questions remain, including the relative benefit or harm of a blood pressure (BP) target and antihypertensive therapy of <120 in very old individuals. Methods The Sydney Memory and Aging Study (n...
Article
Full-text available
Genetic association studies have identified 44 common genome-wide significant risk loci for late-onset Alzheimer's disease (LOAD). However, LOAD genetic architecture and prediction are unclear. Here we estimate the optimal P-threshold (Poptimal) of a genetic risk score (GRS) for prediction of LOAD in three independent datasets comprising 676 cases...
Article
Full-text available
Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individua...
Article
Full-text available
Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individua...
Preprint
Full-text available
This is the first study investigating the genetics of weighted functional brain network graph theory measures from 18,445 participants of the UK Biobank (44-80 years). The eighteen measures studied showed low heritability (mean h ² SNP =0.12) and were highly genetically correlated. Genome-wide association studies for these measures observed 14 sign...
Article
Full-text available
Background: Dementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied. Methods: We harmonized and pooled baseline data from 11 population-based cohorts from 11 countries ove...
Article
Full-text available
The critical role of blood lipids in a broad range of health and disease states is well recognised but less explored is the interplay of genetics and environment within the broader blood lipidome. We examined heritability of the plasma lipidome among healthy older-aged twins (75 monozygotic/55 dizygotic pairs) enrolled in the Older Australian Twins...
Article
Full-text available
The critical role of blood lipids in a broad range of health and disease states is well recognised but less explored is the interplay of genetics and environment within the broader blood lipidome. We examined heritability of the plasma lipidome among healthy older-aged twins (75 monozygotic/55 dizygotic pairs) enrolled in the Older Australian Twins...
Article
Full-text available
The critical role of blood lipids in a broad range of health and disease states is well recognised but less explored is the interplay of genetics and environment within the broader blood lipidome. We examined heritability of the plasma lipidome among healthy older-aged twins (75 monozygotic/55 dizygotic pairs) enrolled in the Older Australian Twins...
Article
Background and purpose: Periventricular white matter hyperintensities (WMH; PVWMH) and deep WMH (DWMH) are regional classifications of WMH and reflect proposed differences in cause. In the first study, to date, we undertook genome-wide association analyses of DWMH and PVWMH to show that these phenotypes have different genetic underpinnings. Metho...
Article
Full-text available
Vascular dementia (VaD) is a complex neurocognitive disorder secondary to a variety of cerebrovascular lesions. Numerous studies have shown that lipid metabolism is involved in the pathobiology of the disease. To examine the plasma lipid profiles in VaD, with the expectation of reliable lipid biomarkers for VaD emerging. 49 VaD patients and 48 heal...
Preprint
Full-text available
Background DNA methylation-based biological age (DNAm age) is potentially an important biomarker for adult health. Studies in specific age ranges have found widely varying results about its causes of variation. We investigated these causes across the lifespan. Methods We pooled genome-wide DNA methylation data for 4,217 people aged 0-92 years from...
Article
Full-text available
Background: Peripheral blood microRNAs (miRNA) have been identified as potential biomarkers for Alzheimer's disease (AD). Study results have generally been inconsistent and limited by sample heterogeneity. The aim of this study is to establish candidate blood miRNA biomarkers for AD by comparing differences in miRNA expression between participants...
Preprint
Full-text available
The critical role of blood lipids in a broad range of health and disease states is well recognised, while an understanding of the complex genetic regulation of lipid homeostasis is emerging. Traditional blood lipids (LDL-C, HDL-C and triglycerides) are known to be substantially regulated by genetic variation. Less well explored is the interplay of...
Preprint
Full-text available
Human brain structure changes throughout our lives. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental, and neurodegenerative diseases. While heritable, specific loci in the genome that influence these rates are largely unknown. Here, we sought to find common genetic variants that affect rates of b...
Article
Trans-ethnic study shows promise in the identification of genetic commonalities and differences for the contribution of traits to lifespan across genetically diverse populations.
Article
We have carried out meta-analyses of genome-wide association studies (GWAS) (n = 23 784) of the first two principal components (PCs) that group together cortical regions with shared variance in their surface area. PC1 (global) captured variations of most regions, whereas PC2 (visual) was specific to the primary and secondary visual cortices. We ide...
Article
This systematic review examines the genetic and epigenetic factors associated with resting-state functional connectivity (RSFC) in healthy human adult brains across the lifespan, with a focus on genes associated with Alzheimer’s disease (AD). There were 58 studies included. The key findings are: (i) genetic factors have a low to moderate contributi...
Article
Full-text available
Prior to and following the publication of this article the authors noted that the complete list of authors was not included in the main article and was only present in Supplementary Table 1. The author list in the original article has now been updated to include all authors, and Supplementary Table 1 has been removed. All other supplementary files...
Article
Background: At present, no predictive markers for Major Depressive Disorder (MDD) exist. The search for such markers has been challenging due to clinical and molecular heterogeneity of MDD, the lack of statistical power in studies and suboptimal statistical tools applied to multidimensional data. Machine learning is a powerful approach to mitigate...
Preprint
Background: Peripheral blood microRNAs (miRNA) have been identified as potential biomarkers for Alzheimer’s disease (AD). Study results have generally been inconsistent and limited by sample heterogeneity. The aim of this study is to establish candidate blood miRNA biomarkers for AD by comparing differences in miRNA expression between participants...
Article
Full-text available
Machine learning methods show promise to translate univariate biomarker findings into clinically useful multivariate decision support systems. At current, works in major depressive disorder have predominantly focused on neuroimaging and clinical predictor modalities, with genetic, blood-biomarker, and cardiovascular modalities lacking. In addition,...