Hieab Adams

• MD PhD
• Professor at Erasmus MC

The hippocampus, crucial in cognitive aging and Alzheimer's disease (AD), shows early atrophy during disease progression. This study investigates 5-year trajectories of hippocampal volumes across AD stages, focusing on genetic predisposition to AD and their impact on hippocampal atrophy. Analyzing data from 1,051 participants in the ADNI, we found...

Peak width of skeletonized mean diffusivity (PSMD) is an emerging automated diffusion imaging marker showing clinically relevant changes in cerebral small vessel disease (cSVD), a leading cause of stroke and dementia with no mechanism-based treatment. We conducted a genome-wide association study of PSMD in 58,403 participants from 24 population-bas...

Background Commissural tracts are the white matter fibre bundles intercommunicating left and right brain hemispheres. They integrate many cognitive functions such as memory, verbal processing, motor and perceptual skills. Also, commissures connect specific layers of cortical neurons that are also lost in Alzheimer’s disease (AD) and other neurodege...

Background Current evidence suggests that hippocampal subfields have partially different genetic architecture and may improve the sensitivity of the detection of Alzheimer’s disease (AD). In this study, we investigated whether genetic predisposition to AD contributes to the accelerated rate of hippocampal volume atrophy across sex and AD stages and...

Background Current evidence suggests that hippocampal subfields have partially different genetic architecture and may improve the sensitivity of the detection of Alzheimer’s disease (AD). In this study, we investigated whether genetic predisposition to AD contributes to the accelerated rate of hippocampal volume atrophy across sex and AD stages and...

Background It is estimated that at least two‐thirds of the world lacks access to neuroimaging, including Magnetic Resonance Imaging (MRI). Yet neuroimaging is one of the most informative tools for neuroscience, potentially biasing advances toward populations with access to this technology. This is evident in Alzheimer’s disease (AD) research, where...

Background Commissural tracts are the white matter fibre bundles intercommunicating left and right brain hemispheres. They integrate many cognitive functions such as memory, verbal processing, motor and perceptual skills. Also, commissures connect specific layers of cortical neurons that are also lost in Alzheimer’s disease (AD) and other neurodege...

Background Current evidence suggests that hippocampal subfields have partially different genetic architecture and may improve the sensitivity of the detection of Alzheimer’s disease (AD). In this study, we investigated whether genetic predisposition to AD contributes to the accelerated rate of hippocampal volume atrophy across sex and AD stages and...

Introduction Disease susceptibility of chronic axonal polyneuropathy is not fully explained by clinical risk factors. Therefore, we determined the contribution of common genetic variants in chronic axonal polyneuropathy in the general population. Methods This study was performed in two population-based studies. Polyneuropathy diagnosis was based o...

Cerebral small vessel disease (cSVD) is a leading cause of stroke and dementia with no specific mechanism-based treatment. We used Mendelian randomization to combine a unique cerebrospinal fluid (CSF) and plasma pQTL resource with the latest European-ancestry GWAS of MRI-markers of cSVD (white matter hyperintensities, perivascular spaces). We descr...

Importance Vascular disease is a treatable contributor to dementia risk, but the role of specific markers remains unclear, making prevention strategies uncertain. Objective To investigate the causal association between white matter hyperintensity (WMH) burden, clinical stroke, blood pressure (BP), and dementia risk, while accounting for potential...

Background Imaging genetics studies commonly assess the individual association between genetic information and brain features without considering joint brain modulations. The aim of this study was to explore the structural variation of the brain at different stages of Alzheimer’s disease (AD), depending on the genetic predisposition to AD. Method...

Background Hippocampal atrophy is one of the most characteristic biomarkers of Alzheimer’s disease (AD), and its genetic basis, as well as that of its distinct subfields, is of current interest. However, hippocampal subfields have so far only been assessed largely unrelated to brain atrophy, and the majority of studies were focused on general popul...

Background Hippocampal atrophy is one of the most characteristic biomarkers of Alzheimer’s disease (AD), and its genetic basis, as well as that of its distinct subfields, is of current interest. However, hippocampal subfields have so far only been assessed largely unrelated to brain atrophy, and the majority of studies were focused on general popul...

Background Imaging genetics studies commonly assess the individual association between genetic information and brain features without considering joint brain modulations. The aim of this study was to explore the structural variation of the brain at different stages of Alzheimer’s disease (AD), depending on the genetic predisposition to AD. Method...

Importance: There is increasing recognition that vascular disease, which can be treated, is a key contributor to dementia risk. However, the contribution of specific markers of vascular disease is unclear and, as a consequence, optimal prevention strategies remain unclear. Objective: To disentangle the causal relation of several key vascular traits...

Skull bone mineral density (SK-BMD) provides a suitable trait for the discovery of key genes in bone biology, particularly to intramembranous ossification, not captured at other skeletal sites. We perform a genome-wide association meta-analysis (n ~ 43,800) of SK-BMD, identifying 59 loci, collectively explaining 12.5% of the trait variance. Associa...

Perivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.6 yr, 96.9% European ancestry) revealed 24 genome-wide significant PVS risk...

Background: Dementia's diagnostic protocols are mostly based on standardised neuroimaging data collected in the Global North from homogeneous samples. In other non-stereotypical samples (participants with diverse admixture, genetics, demographics, MRI signals, or cultural origins), classifications of disease are difficult due to demographic and re...

Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understa...

Perivascular space (PVS) burden is an emerging MRI‐marker of cerebral small vessel disease (cSVD), a leading cause of stroke and dementia. Underlying mechanisms of PVS are unknown. PVS are thought to be related to the glymphatic system, involved in brain clearance of molecules such as amyloid beta. We aimed to decipher the genetic underpinnings of...

Background Cerebral white matter hyperintensities (WMH) on magnetic resonance imaging are markers of cerebral small vessel disease (cSVD), a major risk factor for Alzheimer’s disease and related dementia (ADRD). Despite the successful identification of multiple genetic variants associated with this highly heritable condition, its genetic architectu...

Cerebrovascular disease is increasingly recognized as playing a major role in the pathophysiology of dementia. We aimed to (i) explore the relation of genetically determined white matter hyperintensity burden (WMH) – a common MRI‐marker of covert cerebral small vessel disease (cSVD) – with risk of dementia and Alzheimer disease (AD); (ii) compare i...

Background and objectives: Perivascular spaces (PVS) are emerging markers of cerebral small vessel disease, but research on their determinants has been hampered by conflicting results from small single studies employing heterogeneous rating methods. In this study we therefore aimed to identify determinants of PVS burden in a pooled analysis of mul...

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40–50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes¹. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 inde...

Genome-wide association studies (GWASs) have illustrated that pleiotropy is the norm rather than the exception in the genetic architecture of complex traits. Previous methods have been proposed to investigate cross-trait associations; however, these typically suffer from substantially inflated false positive rates, are limited to associations betwe...

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify associ...

Imaging markers of cerebral small vessel disease provide valuable information on brain health, but their manual assessment is time-consuming and hampered by substantial intra- and interrater variability. Automated rating may benefit biomedical research, as well as clinical assessment, but diagnostic reliability of existing algorithms is unknown. He...

Cerebral white matter hyperintensities on MRI are markers of cerebral small vessel disease, a major risk factor for dementia and stroke. Despite the successful identification of multiple genetic variants associated with this highly heritable condition, its genetic architecture remains incompletely understood. More specifically, the role of DNA meth...

A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We fir...

Background Head circumference is associated with intelligence and tracks from childhood into adulthood. Methods We performed a genome-wide association study meta-analysis and follow-up of head circumference in a total of 29,192 participants between 6 and 30 months of age. Results Seven loci reached genome-wide significance in the combined discove...

Cerebral small vessel disease is a leading cause of stroke and a major contributor to cognitive decline and dementia, but our understanding of specific genes underlying the cause of sporadic cerebral small vessel disease is limited. We report a genome-wide association study and a whole-exome association study on a composite extreme phenotype of cer...

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 ris...

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...

Background: Chronic axonal polyneuropathy is a common disease, but the etiology remains only partially understood. Previous etiologic studies have identified clinical risk factors, but genetic evidence supporting causality between these factors and polyneuropathy are largely lacking. In this study, we investigate whether there is a genetic associa...

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was as...

Understanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding c...

BACKGROUND AND OBJECTIVES Neurofilament light chain (NfL) in blood is a sensitive but non-specific marker of brain injury. This study sought to evaluate associations between NfL concentration and MRI findings of vascular brain injury in older adults. METHODS A longitudinal cohort study included two cranial MRI scans performed about 5 years apart a...

Genetic variants within nearly 1,000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. To expand our understanding of the underl...

Previous genome-wide association studies (GWAS) of stroke, the second leading cause of death, have been conducted in populations of predominantly European ancestry.1,2 We undertook cross-ancestry GWAS meta-analyses of stroke and its subtypes in 110,182 stroke patients (33% non-European) and 1,503,898 control individuals of five ancestries from popu...

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authori...

Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use¹. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels², heart disease remains the leading cause of death worldwi...

A major challenge of genome-wide association studies (GWAS) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We firs...

Measures of information processing speed vary between individuals and decline with age. Studies of aging twins suggest heritability may be as high as 67%. The Illumina HumanExome Bead Chip genotyping array was used to examine the association of rare coding variants with performance on the Digit-Symbol Substitution Test (DSST) in community-dwelling...

Background Non‐Europeans are severely unrepresented in neuroimaging research of neurodegenerative disorders. The uncovering neurodegenerative insights through ethnic diversity (UNITED) consortium was set up to tackle this, aiming to gain insight into the neurodegenerating brain in diverse populations. Large multi‐centre efforts are needed to adequa...

Background The hippocampus is involved in several complex diseases which display sex differences in their prevalence. Therefore, it can be hypothesized that sex‐specific genetic vulnerability in hippocampal formation might partially explain these differences. The aim of this study was to investigate whether the genetic predisposition to several com...

Background Research investigating neuroimaging within neurodegenerative diseases is currently lacking in many ethno‐racial groups. Whilst some racially diverse studies are being carried out within North America many still question its generalizability to global populations. Initiatives are being instigated within South America, and data within Asia...

The interocular distance, or orbital telorism, is a distinctive craniofacial trait that also serves as a clinically informative measure. While its extremes, hypo- and hypertelorism, have been linked to monogenic disorders and are often syndromic, little is known about the genetic determinants of interocular distance within the general population. W...

Skull bone mineral density (SK-BMD) provides a suitable trait for the discovery of genes important to bone biology in general, and particularly for identifying components unique to intramembranous ossification, which cannot be captured at other skeletal sites. We assessed genetic determinants of SK-BMD in 43,800 individuals, identifying 59 genome-w...

Introduction Head motion during magnetic resonance imaging is heritable. Further, it shares phenotypical and genetic variance with body mass index (BMI) and impulsivity. Yet, to what extent this trait is related to single genetic variants and physiological or behavioral features is unknown. We investigated the genetic basis of head motion in a meta...

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...

Orbital telorism, the interocular distance, is clinically informative and in extremes is considered a minor physical anomaly. While its extremes, hypo- and hypertelorism, have been linked to disorders often related to cognitive ability, little is known about the neural correlates of normal variation of telorism within the general population. We der...

Background Subcortical brain structures play a key role in pathological processes of age-related neurodegenerative disorders. Mounting evidence also suggests that early-life factors may have an impact on the development of common late-life neurological diseases, including genetic factors that can influence both brain maturation and neurodegeneratio...

Applying deep learning in population genomics is challenging because of computational issues and lack of interpretable models. Here, we propose GenNet, a novel open-source deep learning framework for predicting phenotypes from genetic variants. In this framework, interpretable and memory-efficient neural network architectures are constructed by emb...

There is clear evidence that hippocampal subfield volumes have partly distinct genetic determinants associated with specific biological processes. The identification of genetic correlates of hippocampal subfield volumes may help to elucidate the mechanisms of neurologic diseases, as well as aging and neurodegenerative processes. However, despite th...

Introduction: There is increasing interest in plasma amyloid beta (Aβ) as an endophenotype of Alzheimer's disease (AD). Identifying the genetic determinants of plasma Aβ levels may elucidate important biological processes that determine plasma Aβ measures. Methods: We included 12,369 non-demented participants from eight population-based studies....

Introduction The increasing evidence of SARS‐CoV‐2 impact on the central nervous system (CNS) raises key questions on its impact for risk of later life cognitive decline, Alzheimer's disease (AD), and other dementia. Methods The Alzheimer's Association and representatives from more than 30 countries—with technical guidance from the World Health...

Orbital telorism, the interocular distance, is a clinically informative and in extremes is considered a mi-nor physical anomaly. While its extremes, hypo- and hypertelorism, have been linked to disorders often related to cognitive ability, little is known about the neural correlates of normal variation of telorism within the general population. We...

Introduction: The increasing evidence of SARS-CoV-2 impact on the central nervous system (CNS) raises key questions on its impact for risk of later life cognitive decline, Alzheimer's disease (AD), and other dementia. Methods: The Alzheimer's Association and representatives from more than 30 countries-with technical guidance from the World Healt...

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...

Background Current evidence supports the involvement of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, and the ε4 allele of APOE gene in hippocampal-dependent functions. Previous studies on the association of Val66Met with whole hippocampal volume included patients of a variety of disorders. However, it remains to be elucidated whe...

Brain-derived neurotrophic factor (BDNF) plays an important role in brain development and function. Substantial amounts of BDNF are present in peripheral blood, and may serve as biomarkers for Alzheimer’s disease incidence as well as targets for intervention to reduce Alzheimer’s disease risk. With the exception of the genetic polymorphism in the B...

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...

Objective: To identify common genetic variants associated with the presence of brain microbleeds (BMB). Methods: We performed genome-wide association studies in 11 population-based cohort studies and 3 case-control or case-only stroke cohorts. Genotypes were imputed to the Haplotype Reference Consortium or 1000 Genomes reference panel. BMB were...

Introduction: Our aim was to study whether systemic metabolites are associated with magnetic resonance imaging (MRI) measures of brain and hippocampal atrophy and white matter hyperintensities (WMH). Methods: We studied associations of 143 plasma-based metabolites with MRI measures of brain and hippocampal atrophy and WMH in three independent co...

Alzheimer’s disease (AD) is a complex, multicausal disorder involving several spatiotemporal scales and scientific domains. While many studies focus on specific parts of this system, the complexity of AD is rarely studied as a whole. In this work, we apply systems thinking to map out known causal mechanisms and risk factors ranging from intracellul...

The size of the human head is determined by growth in the first years of life, while the rest of the body typically grows until early adulthood. Such complex developmental processes are regulated by various genes and growth pathways. Rare genetic syndromes have revealed genes that affect head size, but the genetic drivers of variation in head size...

Blood pressure (BP) was inconsistently associated with migraine and the mechanisms of BP-lowering medications in migraine prophylaxis are unknown. Leveraging large-scale summary statistics for migraine (Ncases/Ncontrols = 59,674/316,078) and BP (N = 757,601), we find positive genetic correlations of migraine with diastolic BP (DBP, rg = 0.11, P = 3...

Background Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood-onset disorder that can persist into adult life. Most genetic studies have focused on investigating biological mechanisms of ADHD during childhood. However, little is known about whether genetic variants associated with ADHD influence structural brain changes throughout adult...

Deep learning is rarely used in population genomics because of the computational burden and challenges in interpreting neural networks. Here, we propose GenNet, a novel open-source deep learning framework for predicting phenotypes from genetic variants. In this framework, interpretable and memory-efficient neural network architectures are construct...

Background and Purpose The prevalence of unruptured intracranial aneurysms (UIAs) in the adult population is ≈3%. Rupture of an intracranial aneurysm can have devastating consequences, which emphasizes the importance of identification of potentially modifiable determinants for the presence and size of UIAs. Our aim was to study the association of a...

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...

Finding automatically multiple lesions in large images is a common problem in medical image analysis. Solving this problem can be challenging if, during optimization, the automated method cannot access information about the location of the lesions nor is given single examples of the lesions. We propose a new weakly supervised detection method using...

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...

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...

Objective Multiple sclerosis (MS) is a neurological disease with a substantial genetic component and immune‐mediated neurodegeneration. Patients with MS show structural brain differences relative to individuals without MS, including smaller regional volumes and alterations in white matter (WM) microstructure. Whether genetic risk for MS is associat...

Background Genetics play a significant role in the etiology of late-life neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, and frontotemporal dementia. Part of the individual differences in risk for these diseases can be traced back decades before the onset of disease symptoms. Previous studies have shown evidence for plausi...

Objective: To test the hypothesis that the inflammatory marker plasma soluble CD14 (sCD14) associates with incident dementia and related endophenotypes in 2 community-based cohorts. Methods: Our samples included the prospective community-based Framingham Heart Study (FHS) and Cardiovascular Health Study (CHS) cohorts. Plasma sCD14 was measured a...

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK...

Localization of focal vascular lesions on brain MRI is an important component of research on the etiology of neurological disorders. However, manual annotation of lesions can be challenging, time-consuming and subject to observer bias. Automated detection methods often need voxel-wise annotations for training. We propose a novel approach for automa...

Deep learning techniques are often criticized to heavily depend on a large quantity of labeled data. This problem is even more challenging in medical image analysis where the annotator expertise is often scarce. We propose a novel data-augmentation method to regularize neural network regressors that learn from a single global label per image. The p...

Multivariate methods have the potential to better capture complex relationships that may exist between different biological levels. Multiple Factor Analysis (MFA) is one of the most popular methods to obtain factor scores and measures of discrepancy between data sets. However, singular value decomposition in MFA is based on PCA, which is adequate o...

Significance The difference between brain age estimated from MRI and chronological age is thought to serve as an important biomarker reflecting pathological processes in the brain. Several recent studies showed the relation between accelerated brain aging and various disorders. However, until now, the utility of such an age difference for preclinic...