Statistical Genetics - Science topic

Many complex traits in humans exhibit sex differences. Recent advances in understanding context-specific genetic effects underscore the imperative for sex-aware genetic analyses to assess the role of sex in the genetic basis of human phenotypes. Despite increasing recognition of the importance of sex as a biological variable, current computational...

Bacteria use gene regulation to dynamically adapt to changes in their environment, including resistance to stress and the occupation of new niches. Gene expression is known to vary within a species pangenome, but the extent to which these changes could be explained by genetic variants in cis non-coding regions has so far been poorly investigated. S...

Population structure is a well-known confounder in statistical genetics, particularly in genome-wide association studies (GWAS), where it can lead to inflated test statistics and spurious associations. Traditional methods, such as principal components (PCs), commonly used to adjust for population structure, are limited in capturing fine-scale, non-...

Background and Objectives The genetic basis of adult-onset multiple sclerosis (MS) is well-studied, but less is known about pediatric-onset MS (pedMS), comprising approximately 5% of all MS onsets. Mendelian randomization (MR) studies have demonstrated evidence for a causal association between MS and both 25-hydroxyvitamin D [25(OH)D] serum levels...

Objectives Based on clinical, biomarker, and genetic data, McGonagle and McDermott suggested that autoimmune and autoinflammatory disorders can be classified as a disease continuum from purely autoimmune to autoinflammatory with mixed diseases in between. However, the genetic architecture of this spectrum has not been systematically described. Here...

Motivation Ancestral Recombination Graphs (ARGs) represent the interwoven paths of genetic ancestry for a set of recombining sequences. The ability to capture the evolutionary history of samples makes ARGs valuable in a wide range of applications in population and statistical genetics. ARG-based approaches are increasingly becoming a part of geneti...

Analytical methods that explore genotype-by-environment interaction (GEI) in multi-environment trials (MET) are essential for the conduction of segregating populations and the release of tropical wheat (Triticum aestivum L.) cultivars. Linear mixed models not only deal with data imbalance, but also allow for the modeling of (co)variances (VCOV), ma...

Gene genealogies represent the ancestry of a sample and are often encoded as ancestral recombination graphs (ARG). It has recently become possible to infer these gene genealogies from sequencing or genotyping data and use them for evolutionary and statistical genetics. Unfortunately, inferred gene genealogies can be noisy and subject to biases, mak...

An early event in plant organogenesis is establishment of a boundary between the stem cell containing meristem and differentiating lateral organ. In maize (Zea mays), evidence suggests a common gene network functions at boundaries of distinct organs and contributes to pleiotropy between leaf angle and tassel branch number, two agronomic traits. To...

Few studies have investigated the effect on the genotypic value of wheat (Triticum aestivum L.) families with the adoption of the additive and epistatic (additive × additive) relationship matrix. The objective of this study is to select F2:3 families of wheat by means of three statistical genetics models (without pedigree information, additive, and...

Heart attacks remain a prominent contributor to mortality rates and impose a considerable economic burden, thereby exerting a profound influence on the overall state of global health. The utilisation of machine learning (ML) and artificial intelligence (AI) technologies has greatly enhanced the advancements in the field of early detection and preve...

Previous genetic studies of human assortative mating have primarily focused on searching for its genomic footprint but have revealed limited insights into its biological and social mechanisms. Combining insights from the economics of the marriage market with advanced tools in statistical genetics, we perform the first genome-wide association study...

Long, identical haplotypes shared between pairs of individuals, known as identity-by-descent (IBD) segments, result from recently shared co-ancestry. Various methods have been developed to utilize IBD sharing for demographic inference in contemporary DNA data. Recent methodological advances have extended the screening for IBD segments to ancient DN...

Psychiatric disorders display high levels of comorbidity and genetic overlap. Genomic methods have shown that even for schizophrenia and bipolar disorder, two disorders long-thought to be etiologically distinct, the majority of genetic signal is shared. Furthermore, recent cross-disorder analyses have uncovered over a hundred pleiotropic loci share...

Historical taxonomic bias has started to be effectively removed in tardigrade taxonomy in the last two decades by the application of modern statistical, genetic and morphological tools. Many of the "old" tardigrade taxa have been redefined, and their succinct original diagnoses-refined, finally resulting in making them properly identifiable and les...

Recent advancements in Parkinson's disease (PD) drug development have been significantly driven by genetic research. Importantly, drugs supported by genetic evidence are more likely to be approved. While genome-wide association studies (GWAS) are a powerful tool to nominate genomic regions associated with certain traits or diseases, pinpointing the...

Brain imaging is a high-content modality that offers dense insights into the structure and pathology of the brain. Existing genetic association studies of brain imaging, typically focusing on a number of individual image-derived phenotypes (IDPs), have successfully identified many genetic loci. Previously, we have created a 128-dimensional Unsuperv...

Genome‐wide association studies (GWAS) statistically assess the association between tens of millions of genetic variants in the whole genome and a phenotype of interest. Genome‐wide association studies enable the elucidation of polygenic inheritance of cancer, in which myriad low‐penetrance genetic variants collectively contribute to a substantial...

A bstract The genome-wide burdens of deletions, loss-of-function mutations, and duplications correlate with many traits. Curiously, for most of these traits, variants that decrease expression have the same genome-wide average direction of effect as variants that increase expression. This seemingly contradicts the intuition that, at individual genes...

By improving disease risk prediction, polygenic risk scores (PRSs) could have a significant impact on health promotion and disease prevention. Due to the historical oversampling of populations with European ancestry for genome-wide association studies, PRSs perform less well in other, understudied populations, leading to concerns that clinical use...

Methods involving summary statistics in genetics can be quite powerful but can be limited in utility. For instance, many post-hoc analyses of disease studies require case and control allele frequencies (AFs), which are not always published. We present two frameworks to derive case and control AFs from GWAS summary statistics using the odds ratio, c...

Background Drug target Mendelian randomization describes the use of genetic variants as instrumental variables for studying the effects of pharmacological agents. The paradigm can be used to inform on all aspects of drug development and has become increasingly popular over the last decade, particularly given the time- and cost-efficiency with which...

Studying the genetic basis of leaf wax composition and its correlation with leaf cuticular conductance (gc) is crucial for improving crop productivity. The leaf cuticle, which comprises a cutin matrix and various waxes, functions as an extracellular hydrophobic layer, protecting against water loss upon stomatal closure. To address the limited under...

In both statistical genetics and phylogenetics, a major goal is to identify correlations between genetic loci or other aspects of the phenotype or environment and a focal trait. In these 2 fields, there are sophisticated but disparate statistical traditions aimed at these tasks. The disconnect between their respective approaches is becoming untenab...

Latin Americans are underrepresented in genetic studies, increasing disparities in personalized genomic medicine. Despite available genetic data from thousands of Latin Americans, accessing and navigating the bureaucratic hurdles for consent or access remains challenging. To address this, we introduce the Genetics of Latin American Diversity (GLAD)...

Estimation of heritability has been a routine in statistical genetics, in particular with the increasing sample size such as biobank-scale data and distributed datasets, the latter of which has increasing concerns of privacy. Recently a randomized Haseman-Elston regression (RHE-reg) has been proposed to estimate SNP-heritability, and given sufficie...

Priprioca (Cyperus ssp.) is an aromatic plant occurring in the Amazon, used in the cosmetics and perfumery industry, the present work aimed to characterize morphological and productive elements of priprioca clones (Cyperus ssp.), Using a randomized block design, With 20 clones, three replicates in subdivided plots with eighteen rhizomes each, condu...

Background Evidence for widespread comorbidity of executive dysfunctions with psychiatric disorders suggests common mechanisms underlying their pathophysiology. However, the shared genetic architectures between psychiatric disorders and executive function (EF) remain poorly understood. Methods Leveraging large genome-wide association study dataset...

Objectives: Based on clinical, biomarker and genetic data, autoimmune and autoinflammatory disorders (AIDs) can be classified as a disease continuum from pure autoinflammatory to pure autoimmune with more complex diseases in between. However, the genetic architecture of AIDs has not been systematically described. Here we investigate the polygenic l...

Autoimmune patients have a significantly increased risk of developing coronary artery disease (CAD) compared to the general population. However, autoimmune patients often lack traditional risk factors for CAD and there is increasing recognition of inflammation in CAD development. In this study, we leveraged genome-wide association study (GWAS) data...

In this paper, we aim to build a platform that will help bridge the gap between high-dimensional computation and wet-lab experimentation by allowing users to interrogate genomic signatures at multiple molecular levels and identify best next actionable steps for downstream decision making. We introduce Multioviz: a publicly accessible R package and...

Genome-wide association studies (GWAS) have accelerated the exploration of genotype–phenotype associations, facilitating the discovery of replicable genetic markers associated with specific traits or complex diseases. This narrative review explores the statistical methodologies developed using GWAS data to investigate relationships between various...

Current literature suggests that people with psychiatric disorders have a higher risk of COVID-19 infection and a worse prognosis of the disease. We aimed to study the genetic contribution to these associations across seven psychiatric disorders as well as a general psychopathology factor (P-factor) and determine whether these are unique or shared...

Genome-wide association studies (GWAS) have accelerated the exploration of genotype-phenotype associations, facilitating the discovery of replicable genetic markers associated with specific traits or complex diseases. This narrative review explores the statistical methodologies developed using GWAS data to investigate relationships between various...

The integration of structural variations (SVs) in statistical genetics provides an opportunity to understand the genetic factors influencing complex human traits and disease. Recent advances in long-read technology and variant calling methods for short reads have improved the accurate discovery and genotyping of SVs, enabling their use in expressio...

Note: This comment has been published at Qeios: John Fuerst, Russell Warne. (2024). Review of: "Heritability within groups is uninformative about differences among groups: Cases from behavioral, evolutionary, and statistical genetics". Qeios. doi:10.32388/VLNL1F.

Background Schizophrenia genome-wide association studies (GWASes) have identified >250 significant loci and prioritized >100 disease-related genes. However, gene prioritization efforts have mostly been restricted to locus-based methods that ignore information from the rest of the genome. Methods To more accurately characterize genes involved in sc...

The historical challenges to bridge the gaps between developmental biology and population or statistical genetics under the explanatory dominance of the Modern Evolutionary Synthesis during the 20th century have been thoroughly documented. However, although several attempts to integrate these fields have been made, most have been deemed unsuccessfu...

Statistical genetic models of genotype-by-environment (G×E) interaction can be divided into two general classes, one on G×E interaction in response to dichotomous environments (e.g., sex, disease-affection status, or presence/absence of an exposure) and the other in response to continuous environments (e.g., physical activity, nutritional measureme...

Many statistical genetics analysis methods make use of GWAS summary statistics. Best statistical practice requires evaluating these methods in simulations against a known truth. Ideally, these simulations should be as realistic as possible. However, simulating summary statistics by first simulating individual genotype and phenotype data is extremel...

Background Approximately 95% of samples analyzed in univariate genome-wide association studies (GWAS) are of European ancestry. This bias toward European ancestry populations in association screening also exists for other analyses and methods that are often developed and tested on European ancestry only. However, existing data in non-European popul...

Systemic Lupus Erythematosus (SLE) is an autoimmune disease with heterogeneous manifestations, including neurological and psychiatric symptoms. Genetic association studies in SLE have been hampered by insufficient sample size and limited power compared to many other diseases. Multiple Sclerosis (MS) is a chronic relapsing autoimmune disease of the...

Studying the genetic basis of leaf wax composition and its correlation with leaf cuticular conductance ( g c ) is crucial for improving crop water-use efficiency. The leaf cuticle, which comprises a cutin matrix and various waxes, functions as an extracellular hydrophobic layer, protecting against water loss upon stomatal closure. To address the li...

Ancestral recombination graphs (ARGs) encode the ensemble of correlated genealogical trees arising from recombination in a compact and efficient structure, and are of fundamental importance in population and statistical genetics. Recent breakthroughs have made it possible to simulate and infer ARGs at biobank scale, and there is now intense interes...

Without the ability to control or randomize environments (or genotypes), it is difficult to determine the degree to which observed phenotypic differences between two groups of individuals are due to genetic vs. environmental differences. However, some have suggested that these concerns may be limited to pathological cases, and methods have appeared...

Breadfruit [Artocarpus altilis (Parkinson) Fosberg] is recognized as a tropical fruit tree crop with great potential to contribute to food and nutrition security in the Caribbean and other tropical regions. However, the genetic diversity and germplasm identification in the Caribbean and elsewhere are poorly understood and documented. This hampers t...

Genomics for rare disease diagnosis has advanced at a rapid pace due to our ability to perform "N-of-1" analyses on individual patients. The increasing sizes of ultra-rare, "N-of-1" disease cohorts internationally newly enables cohort-wide analyses for new discoveries, but well-calibrated statistical genetics approaches for jointly analyzing these...

The broad-banded velvetchin Hapalogenys analis is an economically and scientifically important global temperate and tropical nearshore marine fish. To understand the genetic evolution mechanism of H. analis, simplified genome sequencing analysis was conducted on 82 samples of H. analis from three populations (Akashi, Zhoushan, and Shantou) in the n...

Nutrition and diet are key modifiable risk factors for the rising burden of non-communicable diseases like cardio-vascular diseases and diabetes in low- and middle- income countries (LMICs). The nutritional transition in dietary behaviours in LMICs has most likely contributed to this problem. Although traditionally assumed to be environmental, diet...

Precision medicine models often perform better for populations of European ancestry due to the over-representation of this group in the genomic datasets and large-scale biobanks from which the models are constructed. As a result, prediction models may misrepresent or provide less accurate treatment recommendations for underrepresented populations,...

Recombination events establish the patterns of haplotypic structure in a population and estimates of recombination rates are used in several downstream population and statistical genetic analyses. Using suboptimal maps from distantly related populations may reduce the efficacy of genomic analyses, particularly for underrepresented populations such...

Simple Summary The aim of this study was to describe the basic status of milk production traits of Chinese Holstein cows in Jiangsu, and locate the QTLs and functional genes that affect the five milk production traits (milk yield, milk fat percentage, milk fat yield, milk protein percentage, and milk protein yield) of first-born cows. The five milk...

Cell type proportions vary between individuals and are heritable, as demonstrated by statistical genetic analysis of flow cytometry data. Higher-resolution cell states can be identified by single-cell RNA-sequencing, the scalability of which now makes it applicable to population-scale cohorts. However, the integration of statistical genetic analysi...

Without the ability to control or randomize environments (or genotypes), it is difficult to determine the degree to which observed phenotypic difference between two groups of individuals are due to genetic vs. environmental differences. However, some have suggested that these concerns may be limited to pathological cases, and methods have appeared...

As a result of recombination, adjacent nucleotides can have different paths of genetic inheritance and therefore the genealogical trees for a sample of DNA sequences vary along the genome. The structure capturing the details of these intricately interwoven paths of inheritance is referred to as an ancestral recombination graph (ARG). New developmen...

We briefly review our recently published approach to mining digenic genotype patterns, which consist of two genotypes each originating in a different DNA variant. We do this for a genetic case-control study by evaluating all possible pairs of genotypes, distributing the workload over numerous CPUs (threads) in a high-performance computing environme...

Microbiome scientists critically need modern tools to explore and analyze microbial evolution. Often this involves studying the evolution of microbial genomes as a whole. However, different genes in a single genome can be subject to different evolutionary pressures, which can result in distinct gene-level evolutionary histories. To address this cha...

Here we present an expanded utility of the R package qgg for genetic analyses of complex traits and diseases. One of the major updates of the package is, that it now includes Bayesian Linear Regression (BLR) modeling procedures, which provide a unified framework for mapping of genetic variants, estimation of heritability and genomic prediction from...

Background: While brainstem regions are central regulators of blood pressure, the neuronal mechanisms underlying their role in hypertension remain poorly understood. Here, we investigated the structural and genetic relationships between global and regional brainstem volumes and blood pressure. Methods: Using magnetic resonance imaging data from n=3...

Precision medicine models often perform better for populations of European ancestry due to the over-representation of this group in the genomic datasets and large-scale biobanks from which the models are constructed. As a result, prediction models may misrepresent or provide less accurate treatment recommendations for underrepresented populations,...

In this paper, we aim to build a tool that will help bridge the gap between high-dimensional computation and wet-lab experimentation by allowing users to interrogate genomic signatures at multiple molecular levels and identify best next actionable steps for downstream decision making. We introduce Multioviz: a publicly accessible R package and web...

An edited volume that looks at the state of psychiatric genetics and how to chart a path forward. In this edited collection—experts from psychiatric and statistical genetics, neurobiology, and clinical medicine—investigate whether and how to pursue the discovery of additional genetic risk factors for mental illnesses. Using the existing knowledge a...

An edited volume that looks at the state of psychiatric genetics and how to chart a path forward. In this edited collection—experts from psychiatric and statistical genetics, neurobiology, and clinical medicine—investigate whether and how to pursue the discovery of additional genetic risk factors for mental illnesses. Using the existing knowledge a...

An edited volume that looks at the state of psychiatric genetics and how to chart a path forward. In this edited collection—experts from psychiatric and statistical genetics, neurobiology, and clinical medicine—investigate whether and how to pursue the discovery of additional genetic risk factors for mental illnesses. Using the existing knowledge a...

An edited volume that looks at the state of psychiatric genetics and how to chart a path forward. In this edited collection—experts from psychiatric and statistical genetics, neurobiology, and clinical medicine—investigate whether and how to pursue the discovery of additional genetic risk factors for mental illnesses. Using the existing knowledge a...

An edited volume that looks at the state of psychiatric genetics and how to chart a path forward. In this edited collection—experts from psychiatric and statistical genetics, neurobiology, and clinical medicine—investigate whether and how to pursue the discovery of additional genetic risk factors for mental illnesses. Using the existing knowledge a...

An edited volume that looks at the state of psychiatric genetics and how to chart a path forward. In this edited collection—experts from psychiatric and statistical genetics, neurobiology, and clinical medicine—investigate whether and how to pursue the discovery of additional genetic risk factors for mental illnesses. Using the existing knowledge a...

An edited volume that looks at the state of psychiatric genetics and how to chart a path forward. In this edited collection—experts from psychiatric and statistical genetics, neurobiology, and clinical medicine—investigate whether and how to pursue the discovery of additional genetic risk factors for mental illnesses. Using the existing knowledge a...

An edited volume that looks at the state of psychiatric genetics and how to chart a path forward. In this edited collection—experts from psychiatric and statistical genetics, neurobiology, and clinical medicine—investigate whether and how to pursue the discovery of additional genetic risk factors for mental illnesses. Using the existing knowledge a...

Most human complex phenotypes result from multiple genetic and environmental factors and their interactions. Understanding the mechanisms by which genetic and environmental factors interact offers valuable insights into the genetic architecture of complex traits and holds great potential for advancing precision medicine. The emergence of large popu...

Analysis of natural diversity in wild/cultivated plants can be used to understand the genetic basis for plant breeding programs. Recent advancements in DNA sequencing have expanded the possibilities for genetically altering essential features. There have been several recently disclosed statistical genetic methods for discovering the genes impacting...

Motivation: Existing methods for simulating synthetic genotype and phenotype datasets have limited scalability, constraining their usability for large-scale analyses. Moreover, a systematic approach for evaluating synthetic data quality and a benchmark synthetic dataset for developing and evaluating methods for polygenic risk scores are lacking....

The number of Genome-Wide Association Studies (GWAS) has been growing rapidly in recent years due to developments in genotyping and sequencing platforms. When applied to quantitative traits, these and other statistical genetics approaches require large amounts of consistently and accurately measured phenotypes. Here, we introduce a computational to...

An early event in plant organogenesis is establishment of a boundary between the meristem and differentiating lateral organ. In maize ( Zea mays ), evidence suggests a common gene network functions at boundaries of distinct organs and contributes to pleiotropy between leaf angle and tassel branch number, two agronomic traits. To identify developmen...

A bstract Microbiome scientists critically need modern tools to explore and analyze microbial evolution. Often this involves studying the evolution of microbial genomes as a whole. However, different genes in a single genome can be subject to different evolutionary pressures, which can result in distinct gene-level evolutionary histories. To addres...

The glaucomas are a group of optic neuropathies characterized by progressive degeneration of retinal ganglion cells. Glaucoma affects more than 70 million people worldwide, making it the leading cause of irreversible blindness in the world. Glaucoma can remain asymptomatic until it is severe, resulting in a high likelihood that the number of affect...

Background: The correlation between human gut microbiota and psychiatric diseases has long been recognized. Based on the heritability of the microbiome, genome-wide association studies on human genome and gut microbiome (mbGWAS) have revealed important host-microbiome interactions. However, establishing causal relationships between specific gut mi...

To better capture the polygenic architecture of Alzheimer’s disease (AD), we developed a joint genetic score, MetaGRS. We incorporated genetic variants for AD and 24 other traits from two independent cohorts, NACC ( n = 3,174, training set) and UPitt ( n = 2,053, validation set). One standard deviation increase in the MetaGRS is associated with abo...

Rare or de novo variants have substantial contribution to human diseases, but the statistical power to identify risk genes by rare variants is generally low due to rarity of genotype data. Previous studies have shown that risk genes usually have high expression in relevant cell types, although for many conditions the identity of these cell types ar...

Recombination events establish the patterns of haplotypic structure in a population and estimates of recombination rates are used in several downstream population and statistical genetic analyses. However, the recombination landscape of populations not represented in the 1000 Genomes Project (1KGP) is poorly understood. Using suboptimal maps from d...

Background: Approximately 95% of samples analyzed in univariate genome-wide association studies (GWAS) are of European ancestry. This bias toward European ancestry populations in association screening also exists for other analyses and methods that are often developed and tested on European ancestry only. However, existing data in non-European popu...

Teaching statistics through engaging applications to contemporary large-scale datasets is essential to attracting students to the field. To this end, we developed a hands-on, week-long workshop for senior high-school or junior undergraduate students, without prior knowledge in statistical genetics but with some basic knowledge in data science, to c...