Genome-Wide Association Study of Age-Related Hearing Loss in CFW Mice Identifies Multiple Genes and Loci, Including Prkag2.

Purpose: Age-related hearing loss (ARHL) is one of the most prevalent conditions affecting the elderly. ARHL is influenced by a combination of environmental and genetic factors; the identification of the genes that confer risk will aid in the prevention and treatment of ARHL. The mouse and human inner ears are functionally and genetically homologous.

Genetic Loci Influencing Cue-Reactivity in Heterogeneous Stock Rats.

Addiction vulnerability is associated with the tendency to attribute incentive salience to reward predictive cues. Both addiction and the attribution of incentive salience are influenced by environmental and genetic factors. To characterize the genetic contributions to incentive salience attribution, we performed a genome-wide association study (GWAS) in a cohort of 1596 heterogeneous stock (HS) rats.

A cost-effective, high-throughput, highly accurate genotyping method for outbred populations.

Affordable sequencing and genotyping methods are essential for large-scale genome-wide association studies. While genotyping microarrays and reference panels for imputation are available for human subjects, nonhuman model systems often lack such options. Our lab previously demonstrated an efficient and cost-effective method to genotype heterogeneous stock rats using double-digest genotyping by sequencing.

A Cost-effective, High-throughput, Highly Accurate Genotyping Method for Outbred Populations.

Affordable sequencing and genotyping methods are essential for large scale genome-wide association studies. While genotyping microarrays and reference panels for imputation are available for human subjects, non-human model systems often lack such options. Our lab previously demonstrated an efficient and cost-effective method to genotype heterogeneous stock rats using double-digest genotyping-by-sequencing.

Causal Genetic Loci for a Motivated Behavior Spectrum Harbor Psychiatric Risk Genes.

Behavioral diversity is critical for population fitness. Individual differences in risk-taking are observed across species, but underlying genetic mechanisms and conservation are largely unknown. We examined dark avoidance in larval zebrafish, a motivated behavior reflecting an approach-avoidance conflict.

An exponential increase in QTL detection with an increased sample size.

Power analyses are often used to determine the number of animals required for a genome-wide association study (GWAS). These analyses are typically intended to estimate the sample size needed for at least 1 locus to exceed a genome-wide significance threshold. A related question that is less commonly considered is the number of significant loci that will be discovered with a given sample size.

Genome-wide association study finds multiple loci associated with intraocular pressure in HS rats.

Elevated intraocular pressure (IOP) is influenced by environmental and genetic factors. Increased IOP is a major risk factor for most types of glaucoma, including primary open angle glaucoma (POAG). Investigating the genetic basis of IOP may lead to a better understanding of the molecular mechanisms of POAG.

Genome-Wide Association Study on Three Behaviors Tested in an Open Field in Heterogeneous Stock Rats Identifies Multiple Loci Implicated in Psychiatric Disorders.

Many personality traits are influenced by genetic factors. Rodents models provide an efficient system for analyzing genetic contribution to these traits. Using 1,246 adolescent heterogeneous stock (HS) male and female rats, we conducted a genome-wide association study (GWAS) of behaviors measured in an open field, including locomotion, novel object interaction, and social interaction.

Genome-Wide Association Study in 3,173 Outbred Rats Identifies Multiple Loci for Body Weight, Adiposity, and Fasting Glucose.

Objective: Obesity is influenced by genetic and environmental factors. Despite the success of human genome-wide association studies, the specific genes that confer obesity remain largely unknown. The objective of this study was to use outbred rats to identify the genetic loci underlying obesity and related morphometric and metabolic traits.

Genome-Wide Association Study in Two Cohorts from a Multi-generational Mouse Advanced Intercross Line Highlights the Difficulty of Replication Due to Study-Specific Heterogeneity.

There has been extensive discussion of the "Replication Crisis" in many fields, including genome-wide association studies (). We explored replication in a mouse model using an advanced intercross line (), which is a multigenerational intercross between two inbred strains. We re-genotyped a previously published cohort of LG/J x SM/J AIL mice (F; n = 428) using a denser marker set and genotyped a new cohort of AIL mice (F; n = 600) for the first time.

Genome-wide Associations Reveal Human-Mouse Genetic Convergence and Modifiers of Myogenesis, CPNE1 and STC2.

Muscle bulk in adult healthy humans is highly variable even after height, age, and sex are accounted for. Low muscle mass, due to fewer and/or smaller constituent muscle fibers, would exacerbate the impact of muscle loss occurring in aging or disease. Genetic variability substantially influences muscle mass differences, but causative genes remain largely unknown.

Global Diversity of the Brachypodium Species Complex as a Resource for Genome-Wide Association Studies Demonstrated for Agronomic Traits in Response to Climate.

The development of model systems requires a detailed assessment of standing genetic variation across natural populations. The Brachypodium species complex has been promoted as a plant model for grass genomics with translation to small grain and biomass crops. To capture the genetic diversity within this species complex, thousands of Brachypodium accessions from around the globe were collected and genotyped by sequencing.

Variation in Leaf Respiration Rates at Night Correlates with Carbohydrate and Amino Acid Supply.

Plant respiration can theoretically be fueled by and dependent upon an array of central metabolism components; however, which ones are responsible for the quantitative variation found in respiratory rates is unknown. Here, large-scale screens revealed 2-fold variation in nighttime leaf respiration rate (R) among mature leaves from an Arabidopsis () natural accession collection grown under common favorable conditions. R variation was mostly maintained in the absence of genetic variation, which emphasized the low heritability of R and its plasticity toward relatively small environmental differences within the sampling regime.

Novel Resampling Improves Statistical Power for Multiple-Trait QTL Mapping.

Multiple-trait analysis typically employs models that associate a quantitative trait locus (QTL) with all of the traits. As a result, statistical power for QTL detection may not be optimal if the QTL contributes to the phenotypic variation in only a small proportion of the traits. Excluding QTL effects that contribute little to the test statistic can improve statistical power.

Using Phenomic Analysis of Photosynthetic Function for Abiotic Stress Response Gene Discovery.

Monitoring the photosynthetic performance of plants is a major key to understanding how plants adapt to their growth conditions. Stress tolerance traits have a high genetic complexity as plants are constantly, and unavoidably, exposed to numerous stress factors, which limits their growth rates in the natural environment. , with its broad genetic diversity and wide climatic range, has been shown to successfully adapt to stressful conditions to ensure the completion of its life cycle.

Hnrnph1 Is A Quantitative Trait Gene for Methamphetamine Sensitivity.

Psychostimulant addiction is a heritable substance use disorder; however its genetic basis is almost entirely unknown. Quantitative trait locus (QTL) mapping in mice offers a complementary approach to human genome-wide association studies and can facilitate environment control, statistical power, novel gene discovery, and neurobiological mechanisms. We used interval-specific congenic mouse lines carrying various segments of chromosome 11 from the DBA/2J strain on an isogenic C57BL/6J background to positionally clone a 206 kb QTL (50,185,512-50,391,845 bp) that was causally associated with a reduction in the locomotor stimulant response to methamphetamine (2 mg/kg, i.