Search results for "Multifactorial Inheritance"
showing 10 items of 26 documents
Genomic processes underlying rapid adaptation of a natural Chironomus riparius population to unintendedly applied experimental selection pressures
2020
Evolve and Resquence (E&R) studies are a useful tool to study genomic processes during rapid adaptation, e.g., in the framework of adaptive responses to global climate change. We applied different thermal regimes to a natural Chironomus riparius (Diptera) population in an E&R framework to infer its evolutionary potential for rapid thermal adaptation. We exposed two replicates to three temperatures each (14°C, 20°C and 26°C) for more than two years, the experiment thus lasting 22, 44 or 65 generations, respectively. The two higher temperatures presented a priori moderate, respectively strong selection pressures. Life-cycle fitness tests revealed no appreciable adaptation to thermal regimes b…
Bacillus thuringiensis Vip3Aa Toxin Resistance in Heliothis virescens (Lepidoptera: Noctuidae)
2017
ABSTRACT Laboratory selection with Vip3Aa of a field-derived population of Heliothis virescens produced >2,040-fold resistance in 12 generations of selection. The Vip3Aa-selected (Vip-Sel)-resistant population showed little cross-resistance to Cry1Ab and no cross-resistance to Cry1Ac. Resistance was unstable after 15 generations without exposure to the toxin. F 1 reciprocal crosses between Vip3Aa-unselected (Vip-Unsel) and Vip-Sel insects indicated a strong paternal influence on the inheritance of resistance. Resistance ranged from almost completely recessive (mean degree of dominance [ h ] = 0.04 if the resistant parent was female) to incompletely dominant (mean h = 0.53 if the resistan…
Consequences of single-locus and tightly linked genomic architectures for evolutionary responses to environmental change
2020
AbstractGenetic and genomic architectures of traits under selection are key factors influencing evolutionary responses. Yet, knowledge of their impacts has been limited by a widespread assumption that most traits are controlled by unlinked polygenic architectures. Recent advances in genome sequencing and eco-evolutionary modelling are unlocking the potential for integrating genomic information into predictions of population responses to environmental change. Using eco-evolutionary simulations, we demonstrate that hypothetical single-locus control of a life history trait produces highly variable and unpredictable harvesting-induced evolution relative to the classically applied multi-locus mo…
Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia
2019
Developmental dyslexia (DD) is one of the most prevalent learning disorders, with high impact on school and psychosocial development and high comorbidity with conditions like attention-deficit hyperactivity disorder (ADHD), depression, and anxiety. DD is characterized by deficits in different cognitive skills, including word reading, spelling, rapid naming, and phonology. To investigate the genetic basis of DD, we conducted a genome-wide association study (GWAS) of these skills within one of the largest studies available, including nine cohorts of reading-impaired and typically developing children of European ancestry (N = 2562–3468). We observed a genome-wide significant effect (p < 1 × 10…
Holocene Selection for Variants Associated With General Cognitive Ability: Comparing Ancient and Modern Genomes
2017
Human populations living during the Holocene underwent considerable microevolutionary change. It has been theorized that the transition of Holocene populations into agrarianism and urbanization brought about culture-gene co-evolution that favored via directional selection genetic variants associated with higher general cognitive ability (GCA). To examine whether GCA might have risen during the Holocene, we compare a sample of 99 ancient Eurasian genomes (ranging from 4.56 to 1.21 kyr BP) with a sample of 503 modern European genomes (Fst= 0.013), using three different cognitive polygenic scores (130 SNP, 9 SNP and 11 SNP). Significant differences favoring the modern genomes were found for al…
Non-invasive stratification of hepatocellular carcinoma risk in non-alcoholic fatty liver using polygenic risk scores
2021
Background & Aims: Hepatocellular carcinoma (HCC) risk stratification in individuals with dysmetabolism is a major unmet need. Genetic predisposition contributes to non-alcoholic fatty liver disease (NAFLD). We aimed to exploit robust polygenic risk scores (PRS) that can be evaluated in the clinic to gain insight into the causal relationship between NAFLD and HCC, and to improve HCC risk stratification. Methods: We examined at-risk individuals (NAFLD cohort, n = 2,566; 226 with HCC; and a replication cohort of 427 German patients with NAFLD) and the general population (UK Biobank [UKBB] cohort, n = 364,048; 202 with HCC). Variants in PNPLA3-TM6SF2-GCKR-MBOAT7 were combined in a hepatic …
Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum
2020
The EUGEI project was supported by the European Community’s Seventh Framework Program under grant agreement no. HEALTH-F2-2009-241909 (Project EU-GEI). Dr O’Donovan is supported by MRC programme grant (G08005009) and an MRC Centre grant (MR/ L010305/1). Dr Rutten was funded by a VIDI award number 91718336 from the Netherlands Scientific Organisation. Drs Guloksuz and van Os are supported by the Ophelia research project, ZonMw grant number: 636340001. Dr Arango was supported by the Spanish Ministry of Science and Innovation; Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/024); CIBERSAM; Madrid Regional Government (B2017/BMD-3740, AGES-CM-2); Fundación Familia Alonso and Fundac…
Replication of previous genome-wide association studies of psychiatric diseases in a large schizophrenia case-control sample from Spain.
2014
Genome wide association studies (GWAS) has allowed the discovery of some interesting risk variants for schizophrenia (SCZ). However, this high-throughput approach presents some limitations, being the most important the necessity of highly restrictive statistical corrections as well as the loss of statistical power inherent to the use of a Single Nucleotide Polymorphism (SNP) analysis approach. These problems can be partially solved through the use of a polygenic approach. We performed a genotyping study in SCZ using 86 previously associated SNPs identified by GWAS of SCZ, bipolar disorder (BPD) and autistic spectrum disorder (ASD) patients. The sample consisted of 3063 independent cases wit…
IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
2018
GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 ca…
A polygenic approach to the association between smoking and schizophrenia.
2021
Smoking prevalence in schizophrenia is considerably larger than in general population, playing an important role in early mortality. We compared the polygenic contribution to smoking in schizophrenic patients and controls to assess if genetic factors may explain the different prevalence. Polygenic risk scores (PRSs) for smoking initiation and four genetically correlated traits were calculated in 1108 schizophrenic patients (64.4% smokers) and 1584 controls (31.1% smokers). PRSs for smoking initiation, educational attainment, body mass index and age at first birth were associated with smoking in patients and controls, explaining a similar percentage of variance in both groups. Attention-defi…