It’s in the Bloody Genes!

2020 ◽  
Vol 23 (2) ◽  
pp. 96-97
Author(s):  
David M. Evans
Keyword(s):  
Blood Cell ◽  
Association Studies ◽  
Cell Types ◽  
Linkage Studies ◽  
Genetic Loci ◽  
Twin Registry ◽  
Cell Concentrations ◽  
Genomewide Association

AbstractBlood cell concentrations for most cell types are highly heritable. Data from Nick Martin’s twin registry provided much of the data for the early heritability and linkage studies of blood cell related traits and have contributed significantly to more recent genomewide association studies that have successfully identified individual genetic loci.

scholarly journals Accurate prediction of cell composition, age, smoking consumption and infection serostatus based on blood DNA methylation profiles

2018 ◽  
Author(s):  
Jacob Bergstedt ◽  
Alejandra Urrutia ◽  
Darragh Duffy ◽  
Matthew L. Albert ◽  
Lluís Quintana-Murci ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Blood Cell ◽  
Regression Models ◽  
Disease Risk ◽  
Association Studies ◽  
Cell Types ◽  
Cellular Heterogeneity ◽  
Cell Composition ◽  
Healthy Donors ◽  
Circulating Levels

DNA methylation is a stable epigenetic alteration that plays a key role in cellular differentiation and gene regulation, and that has been proposed to mediate environmental effects on disease risk. Epigenome-wide association studies have identified and replicated associations between methylation sites and several disease conditions, which could serve as biomarkers in predictive medicine and forensics. Nevertheless, heterogeneity in cellular proportions between the compared groups could complicate interpretation. Reference-based cell-type deconvolution methods have proven useful in correcting epigenomic studies for cellular heterogeneity, but they rely on reference libraries of sorted cells and only predict a limited number of cell populations. Here we leverage >850,000 methylation sites included in the MethylationEPIC array and use elastic net regularized and stability selected regression models to predict the circulating levels of 70 blood cell subsets, measured by standardized flow cytometry in 962 healthy donors of western European descent. We show that our predictions, based on a hundred of methylation sites or lower, are less error-prone than other existing methods, and extend the number of cell types that can be accurately predicted. Application of the same methods to age, smoking consumption and several serological responses to pathogen antigens also provide accurate estimations. Together, our study substantially improves predictions of blood cell composition based on methylation profiles, which will be critical in the emerging field of medical epigenomics.

scholarly journals Influence of Genetic Variants in EGF and Other Genes on Hematological Traits in Korean Populations by a Genome-Wide Approach

2015 ◽  
Vol 2015 ◽  
pp. 1-9
Author(s):  
Yun Kyoung Kim ◽  
Ji Hee Oh ◽  
Young Jin Kim ◽  
Mi Yeong Hwang ◽  
Sanghoon Moon ◽  
...  
Keyword(s):  
Platelet Count ◽  
Blood Cell ◽  
Cell Count ◽  
Ethnic Groups ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Blood Cell Count ◽  
Genetic Loci ◽  
Genome Wide ◽  
A Genome

Hematological traits are important health indicators and are used as diagnostic clinical parameters for human disorders. Recently, genome-wide association studies (GWAS) identified many genetic loci associated with hematological traits in diverse ethnic groups. However, additional GWAS are necessary to elucidate the breadth of genetic variation and the underlying genetic architecture represented by hematological metrics. To identify additional genetic loci influencing hematological traits (such as hematocrit, hemoglobin concentration, white blood cell count, red blood cell count, and platelet count), we conducted GWAS and meta-analyses on data from 12,509 Korean individuals grouped into population-based cohorts. Of interest is EGF, a factor plays a role in the proliferation and differentiation of hematopoietic progenitor cells. We identified a novel EGF variant, which associated with platelet count in our study (Pcombined=2.44×10-15). Our study also replicated 16 genetic associations related to five hematological traits with genome-wide significance (P<5×10-8) that were previously established in other ethnic groups. Of these, variants influencing platelet count are distributed across several genes and have pleiotropic effects in coronary artery disease and dyslipidemia. Our findings may aid in elucidating molecular mechanisms underlying not only hematopoiesis but also inflammatory and cardiovascular diseases.

scholarly journals Assessing the co-variability of DNA methylation across peripheral cells and tissues: Implications for the interpretation of findings in epigenetic epidemiology

PLoS Genetics ◽  
2021 ◽  
Vol 17 (3) ◽  
pp. e1009443
Author(s):  
Eilis Hannon ◽  
Georgina Mansell ◽  
Emma Walker ◽  
Marta F. Nabais ◽  
Joe Burrage ◽  
...  
Keyword(s):  
Dna Methylation ◽  
T Cells ◽  
Blood Cell ◽  
Whole Blood ◽  
Association Studies ◽  
Cell Types ◽  
Peripheral Tissues ◽  
Epigenetic Epidemiology ◽  
Blood Cell Type ◽  
Multiple Cell

Most epigenome-wide association studies (EWAS) quantify DNA methylation (DNAm) in peripheral tissues such as whole blood to identify positions in the genome where variation is statistically associated with a trait or exposure. As whole blood comprises a mix of cell types, it is unclear whether trait-associated DNAm variation is specific to an individual cellular population. We collected three peripheral tissues (whole blood, buccal epithelial and nasal epithelial cells) from thirty individuals. Whole blood samples were subsequently processed using fluorescence-activated cell sorting (FACS) to purify five constituent cell-types (monocytes, granulocytes, CD4+ T cells, CD8+ T cells, and B cells). DNAm was profiled in all eight sample-types from each individual using the Illumina EPIC array. We identified significant differences in both the level and variability of DNAm between different sample types, and DNAm data-derived estimates of age and smoking were found to differ dramatically across sample types from the same individual. We found that for the majority of loci variation in DNAm in individual blood cell types was only weakly predictive of variance in DNAm measured in whole blood, although the proportion of variance explained was greater than that explained by either buccal or nasal epithelial samples. Covariation across sample types was much higher for DNAm sites influenced by genetic factors. Overall, we observe that DNAm variation in whole blood is additively influenced by a combination of the major blood cell types. For a subset of sites, however, variable DNAm detected in whole blood can be attributed to variation in a single blood cell type providing potential mechanistic insight about EWAS findings. Our results suggest that associations between whole blood DNAm and traits or exposures reflect differences in multiple cell types and our data will facilitate the interpretation of findings in epigenetic epidemiology.

The Australian Twin Registry as a Resource For Genetic Studies into Ophthalmic Traits

2012 ◽  
Vol 16 (1) ◽  
pp. 52-57
Author(s):  
Maria Schache ◽  
Paul N. Baird
Keyword(s):  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Linkage Studies ◽  
Genetic Studies ◽  
For Profit ◽  
Not For Profit ◽  
Twin Registry ◽  
Genome Wide ◽  
Broad Overview

The Australian Twin Registry (ATR) is a not-for-profit organization that coordinates research involving Australian twins and researchers. The ATR is one of the largest volunteer registries of its kind and contains over 33,000 twin pairs. The purpose of this review is to provide a broad overview of recent ophthalmic studies that have utilized the ATR for recruitment purposes. Such studies include the Australian Twin Eye Study (ATES) and the Genes in Myopia (GEM) study. The ATES and GEM studies have undertaken studies into the genetic influences on a number of ophthalmic traits through the use of heritability studies, linkage studies, genome-wide association studies, and candidate gene-based studies. An overview of these studies is provided in this review, as well as a description of the recruitment methodologies for both the ATES and GEM studies.

CS01-03 - Genetics of addiction

2011 ◽  
Vol 26 (S2) ◽  
pp. 1769-1769
Author(s):  
M. Munafo
Keyword(s):  
Substance Use ◽  
Candidate Gene ◽  
Genetic Variants ◽  
Association Studies ◽  
Intermediate Phenotype ◽  
Phenotypic Variance ◽  
Linkage Studies ◽  
Adoption Studies ◽  
Comprehensive Overview ◽  
Genomewide Association

It is well known from twin, family and adoption studies that addictive behaviours are under a degree of genetic influence, which is reflected in moderate to high heritability coefficients for these phenotypes. In the last twenty years, considerable effort has been invested in attempting to determine the molecular genetic basis of this influence, with mixed success. While early candidate gene studies for the most part failed to identify genetic variants which were reliably associated with risk of substance use, more recent genomewide association methods have begun to yield promising findings and novel insights into the mechanisms of addictive behaviours.The history of genetic studies of risk of substance use will be presented, including a brief overview of twin, family and adoption studies, and of candidate gene and linkage studies. More recent findings, in particular focusing on genomewide association studies, will be discussed in detail. Finally, emerging findings from gene x environment and intermediate phenotype studies will be highlighted. This presentation will provide a comprehensive overview of the current state of the field of addiction genetics, placed in the historical context of heritability, candidate gene and linkage studies.While the study of the genetics of addictive behaviours remains in relative infancy, some compelling findings are beginning to emerge. Genetic variants which influence the metabolism of specific substances, such as alcohol and nicotine, appear to influence the intake of those substances. A number of genes which encode drug targets also appear to influence drug-taking behaviour, such as the alpha-5 nicotinic acetylcholine receptor subunit, which has been robustly shown to associate with heaviness of smoking. However, the proportion of phenotypic variance explained by these variants remains small. Potential reasons for this will be discussed.

scholarly journals Telomere length varies substantially between blood cell types in a reptile

2020 ◽  
Vol 7 (6) ◽  
pp. 192136 ◽  
Author(s):  
Mats Olsson ◽  
Nicholas J. Geraghty ◽  
Erik Wapstra ◽  
Mark Wilson
Keyword(s):  
Blood Cell ◽  
Telomere Length ◽  
Whole Blood ◽  
Phylogenetic Analyses ◽  
Natural Populations ◽  
Cell Types ◽  
Tissue Type ◽  
Telomeric Dna ◽  
Blood Cell Type ◽  
Widespread Phenomenon

Telomeres are repeat sequences of non-coding DNA-protein molecules that cap or intersperse metazoan chromosomes. Interest in telomeres has increased exponentially in recent years, to now include their ongoing dynamics and evolution within natural populations where individuals vary in telomere attributes. Phylogenetic analyses show profound differences in telomere length across non-model taxa. However, telomeres may also differ in length within individuals and between tissues. The latter becomes a potential source of error when researchers use different tissues for extracting DNA for telomere analysis and scientific inference. A commonly used tissue type for assessing telomere length is blood, a tissue that itself varies in terms of nuclear content among taxa, in particular to what degree their thrombocytes and red blood cells (RBCs) contain nuclei or not. Specifically, when RBCs lack nuclei, leucocytes become the main source of telomeric DNA. RBCs and leucocytes differ in lifespan and how long they have been exposed to ‘senescence' and erosion effects. We report on a study in which cells in whole blood from individual Australian painted dragon lizards ( Ctenophorus pictus ) were identified using flow cytometry and their telomere length simultaneously measured. Lymphocyte telomeres were on average 270% longer than RBC telomeres, and in azurophils (a reptilian monocyte), telomeres were more than 388% longer than those in RBCs. If this variation in telomere length among different blood cell types is a widespread phenomenon, and DNA for comparative telomere analyses are sourced from whole blood, evolutionary inference of telomere traits among taxa may be seriously complicated by the blood cell type comprising the main source of DNA.

scholarly journals Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Daniel L. McCartney ◽  
Josine L. Min ◽  
Rebecca C. Richmond ◽  
Ake T. Lu ◽  
Maria K. Sobczyk ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Genome Wide Association ◽  
Biological Aging ◽  
Genome Wide Association Studies ◽  
Genetic Loci ◽  
Biomarkers Of Aging ◽  
Genome Wide ◽  
Shared Genetic

Abstract Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.

scholarly journals Genetic architecture of schizophrenia: a review of major advancements

2021 ◽  
pp. 1-10
Author(s):  
Sophie E. Legge ◽  
Marcos L. Santoro ◽  
Sathish Periyasamy ◽  
Adeniran Okewole ◽  
Arsalan Arsalan ◽  
...  
Keyword(s):  
Genetic Architecture ◽  
Association Studies ◽  
Copy Number Variants ◽  
Risk Scores ◽  
Genome Wide Association Studies ◽  
Loss Of Function ◽  
Genetic Loci ◽  
Significant Enrichment ◽  
High Heritability ◽  
Coding Variants

Abstract Schizophrenia is a severe psychiatric disorder with high heritability. Consortia efforts and technological advancements have led to a substantial increase in knowledge of the genetic architecture of schizophrenia over the past decade. In this article, we provide an overview of the current understanding of the genetics of schizophrenia, outline remaining challenges, and summarise future directions of research. World-wide collaborations have resulted in genome-wide association studies (GWAS) in over 56 000 schizophrenia cases and 78 000 controls, which identified 176 distinct genetic loci. The latest GWAS from the Psychiatric Genetics Consortium, available as a pre-print, indicates that 270 distinct common genetic loci have now been associated with schizophrenia. Polygenic risk scores can currently explain around 7.7% of the variance in schizophrenia case-control status. Rare variant studies have implicated eight rare copy-number variants, and an increased burden of loss-of-function variants in SETD1A, as increasing the risk of schizophrenia. The latest exome sequencing study, available as a pre-print, implicates a burden of rare coding variants in a further nine genes. Gene-set analyses have demonstrated significant enrichment of both common and rare genetic variants associated with schizophrenia in synaptic pathways. To address current challenges, future genetic studies of schizophrenia need increased sample sizes from more diverse populations. Continued expansion of international collaboration will likely identify new genetic regions, improve fine-mapping to identify causal variants, and increase our understanding of the biology and mechanisms of schizophrenia.

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