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Pesticide Biochemistry and Physiology Jun 2024Lambda-cyhalothrin, a representative pyrethroid insecticide widely used for Spodoptera frugiperda control in China, poses challenges due to the development of...
Lambda-cyhalothrin, a representative pyrethroid insecticide widely used for Spodoptera frugiperda control in China, poses challenges due to the development of resistance. This study investigates the realized heritability, inheritance pattern, cross-resistance, and resistance mechanisms to lambda-cyhalothrin. After 21 generations of selection, the lambda-cyhalothrin-resistant strain (G21) developed a 171.11-fold resistance compared to a relatively susceptible strain (RS-G9), with a realized heritability (h) of 0.11. Cross-resistance assays revealed that lambda-cyhalothrin-resistant strains showed no significant cross-resistance to the majority of tested insecticides. Genetic analysis indicated that lambda-cyhalothrin resistance in S. frugiperda was autosomal, incompletely dominant, and polygenic inheritance. The P450 enzyme inhibitor PBO significantly enhanced lambda-cyhalothrin toxicity in the resistant strains. Compared with the RS-G9 strain, the P450 enzyme activity was significantly increased and multiple P450 genes were significantly up-regulated in the lambda-cyhalothrin-resistant strains. RNAi targeting the most overexpressed P450 genes (CYP337B5 and CYP321B1) significantly increased the susceptibility of resistant S. frugiperda larvae to lambda-cyhalothrin. This study provides comprehensive insights into lambda-cyhalothrin resistance in S. frugiperda, and the results are helpful for developing effective resistance management strategies of this pest.
Topics: Animals; Pyrethrins; Nitriles; Spodoptera; Insecticide Resistance; Insecticides; Cytochrome P-450 Enzyme System; RNA Interference; Larva
PubMed: 38879318
DOI: 10.1016/j.pestbp.2024.105916 -
Pesticide Biochemistry and Physiology Jun 2024Pesticides remain a cornerstone in pest control, yet their extensive and irrational use also fuel the evolution of resistance. This review analyzes globally published... (Review)
Review
Pesticides remain a cornerstone in pest control, yet their extensive and irrational use also fuel the evolution of resistance. This review analyzes globally published experimental data spanning from the 1970s to 2023 to focus on how phenotypic and underlying genotypic variations are shaped during the selective response. The discussion commences with an examination of sex-linked/maternal resistance. Observations related to maternal inheritance have enriched our understanding of pesticide mode of action, notably exemplified by bifenazate. However, the predominant control of the resistant phenotype is attributed to autosomal traits, with a high prevalence of dominance and monogenic inheritance observed, also evident in field strains. This observation raises concerns regarding resistance management strategies due to their potential to accelerate the spread of resistance. The interplay between dominance levels and monogenic inheritance is further explored, with dominant traits being significantly more prevalent in polygenic inheritance. This observation may be attributed to the accumulation of enhanced metabolism. Notably, further analysis indicated that field strains exhibit a higher incidence of monogenic inheritance compared to other selected strains, aligning with established theoretical frameworks. In conclusion, the genetic architecture of resistance warrants increased research focus for its pivotal role in guiding resistance management strategies and advancing fundamental research.
Topics: Pesticides; Animals; Insecticide Resistance; Phenotype
PubMed: 38879312
DOI: 10.1016/j.pestbp.2024.105964 -
Molecular Autism Jun 2024Positive assortative mating (AM) in several neuropsychiatric traits, including autism, has been noted. However, it is unknown whether the pattern of AM is different in...
BACKGROUND
Positive assortative mating (AM) in several neuropsychiatric traits, including autism, has been noted. However, it is unknown whether the pattern of AM is different in phenotypically defined autism subgroups [e.g., autism with and without intellectually disability (ID)]. It is also unclear what proportion of the phenotypic AM can be explained by the genetic similarity between parents of children with an autism diagnosis, and the consequences of AM on the genetic structure of the population.
METHODS
To address these questions, we analyzed two family-based autism collections: the Simons Foundation Powering Autism Research for Knowledge (SPARK) (1575 families) and the Simons Simplex Collection (SSC) (2283 families).
RESULTS
We found a similar degree of phenotypic and ancestry-related AM in parents of children with an autism diagnosis regardless of the presence of ID. We did not find evidence of AM for autism based on autism polygenic scores (PGS) (at a threshold of |r|> 0.1). The adjustment of ancestry-related AM or autism PGS accounted for only 0.3-4% of the fractional change in the estimate of the phenotypic AM. The ancestry-related AM introduced higher long-range linkage disequilibrium (LD) between single nucleotide polymorphisms (SNPs) on different chromosomes that are highly ancestry-informative compared to SNPs that are less ancestry-informative (D on the order of 1 × 10).
LIMITATIONS
We only analyzed participants of European ancestry, limiting the generalizability of our results to individuals of non-European ancestry. SPARK and SSC were both multicenter studies. Therefore, there could be ancestry-related AM in SPARK and SSC due to geographic stratification. The study participants from each site were unknown, so we were unable to evaluate for geographic stratification.
CONCLUSIONS
This study showed similar patterns of AM in autism with and without ID, and demonstrated that the common genetic influences of autism are likely relevant to both autism groups. The adjustment of ancestry-related AM and autism PGS accounted for < 5% of the fractional change in the estimate of the phenotypic AM. Future studies are needed to evaluate if the small increase of long-range LD induced by ancestry-related AM has impact on the downstream analysis.
Topics: Humans; Autistic Disorder; Phenotype; Male; Female; Linkage Disequilibrium; Multifactorial Inheritance; Child; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Adult; Intellectual Disability
PubMed: 38877467
DOI: 10.1186/s13229-024-00605-5 -
Journal of the American Heart... Jun 2024
Topics: Humans; Female; Coronary Artery Disease; Sex Factors; Prognosis; Multifactorial Inheritance; Risk Assessment; Genetic Predisposition to Disease; Risk Factors; Male
PubMed: 38874071
DOI: 10.1161/JAHA.123.034946 -
Revue Medicale de Liege Jun 2024Despite screening programmes, numerous clinical studies and new breast imaging techniques, breast cancer incidence for women continues to rise. The arrival of predictive... (Review)
Review
Despite screening programmes, numerous clinical studies and new breast imaging techniques, breast cancer incidence for women continues to rise. The arrival of predictive and personalized medicine could clearly redefine our screening recommendations. One promising approach to improving screening would be to use tools to predict the risk of developing breast cancer, including polygenic risk scores (PRS). This approach will enable us to offer women risk-based screening by adapting the frequency, type and age of screening. This article reviews some definitions of the PRS and breast cancer screening. We also explain the risk assessment models that have been developed and the various studies underway on personalized screening.
Topics: Humans; Breast Neoplasms; Female; Early Detection of Cancer; Risk Assessment; Preventive Medicine; Multifactorial Inheritance; Genetic Predisposition to Disease; Genetic Risk Score
PubMed: 38869126
DOI: No ID Found -
Cureus Jun 2024Type 2 diabetes mellitus (T2DM) is a consequence of insulin resistance, insulin deficiency, or both. It is usually seen in adults and is a consequence of genetic...
Metformin Monotherapy With and Without Lifestyle Changes Affects Anthropometric Parameters, Blood Pressure, Blood Glucose, and Lipid Profile in Indian Patients With Newly Diagnosed Type 2 Diabetes.
INTRODUCTION
Type 2 diabetes mellitus (T2DM) is a consequence of insulin resistance, insulin deficiency, or both. It is usually seen in adults and is a consequence of genetic (polygenic inheritance), endogenous (obesity and or hormonal factors), and environmental factors (e.g., obesogenic environment, endocrine disrupting chemicals, stress, and medicines). The prevalence of T2DM has increased over the past few decades. South Asians, including Indians, are more prone to central adiposity and develop lifestyle diseases like T2DM at body mass index values lower than those considered normal for the Western population. Generally, the first line of treatment is metformin monotherapy with lifestyle changes in patients with T2DM. Most of the research conducted on this drug is on Western subjects. Since the Indian population has genetic differences in the site of deposition of adipose and is more prone to develop lifestyle diseases, the effect of metformin may be different in Indians.
METHODS
Seventy-one (34 female, non-pregnant, non-lactating) adults with newly diagnosed T2DM were recruited in this short-duration pilot study after obtaining written informed consent. Patients regularly taking any drug were excluded, as were patients with chronic comorbidities. Treatment was initiated with metformin 500 mg OD. Lifestyle changes were recommended according to the age and physical condition of the patients. Anthropometric parameters (age, weight, height, BMI, waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR)), blood pressure, glycemic status (fasting and 2 h PP glucose and HbA1c), and lipid profile of the subjects were recorded before initiating and six months after initiating metformin monotherapy with lifestyle changes.
RESULTS
Small but statistically significant improvements were observed in the WHR,WHtR, blood pressure, blood glucose, and glycated hemoglobin. Although improvement was also observed in weight and lipid profile, these changes were not statistically significant.
CONCLUSION
This study shows that metformin monotherapy with lifestyle changes is suitable for patients of Indian origin and results in improvement in the WHR, WHtR, blood pressure, plasma glucose, and glycated hemoglobin.
PubMed: 38868550
DOI: 10.7759/cureus.62131 -
Nature Communications Jun 2024Polygenic scores (PGSs) offer the ability to predict genetic risk for complex diseases across the life course; a key benefit over short-term prediction models. To...
Polygenic scores (PGSs) offer the ability to predict genetic risk for complex diseases across the life course; a key benefit over short-term prediction models. To produce risk estimates relevant to clinical and public health decision-making, it is important to account for varying effects due to age and sex. Here, we develop a novel framework to estimate country-, age-, and sex-specific estimates of cumulative incidence stratified by PGS for 18 high-burden diseases. We integrate PGS associations from seven studies in four countries (N = 1,197,129) with disease incidences from the Global Burden of Disease. PGS has a significant sex-specific effect for asthma, hip osteoarthritis, gout, coronary heart disease and type 2 diabetes (T2D), with all but T2D exhibiting a larger effect in men. PGS has a larger effect in younger individuals for 13 diseases, with effects decreasing linearly with age. We show for breast cancer that, relative to individuals in the bottom 20% of polygenic risk, the top 5% attain an absolute risk for screening eligibility 16.3 years earlier. Our framework increases the generalizability of results from biobank studies and the accuracy of absolute risk estimates by appropriately accounting for age- and sex-specific PGS effects. Our results highlight the potential of PGS as a screening tool which may assist in the early prevention of common diseases.
Topics: Humans; Male; Female; Multifactorial Inheritance; Incidence; Middle Aged; Genetic Predisposition to Disease; Adult; Aged; Diabetes Mellitus, Type 2; Risk Factors; Risk Assessment; Global Burden of Disease; Sex Factors; Age Factors
PubMed: 38866767
DOI: 10.1038/s41467-024-48938-2 -
Expert Review of Endocrinology &... Jul 2024Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive condition. Effective treatment is important as patients are at risk for severe and potentially... (Review)
Review
INTRODUCTION
Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive condition. Effective treatment is important as patients are at risk for severe and potentially fatal acute pancreatitis. We review recent developments in pharmacologic treatment for FCS, namely biological inhibitors of apolipoprotein (apo) C-III and angiopoietin-like protein 3 (ANGPTL3).
AREAS COVERED
FCS follows a biallelic inheritance pattern in which an individual inherits two pathogenic loss-of-function alleles of one of the five causal genes - (in 60-80% of patients), , , , and - leading to the absence of lipolytic activity. Patients present from childhood with severely elevated triglyceride (TG) levels >10 mmol/L. Most patients with severe hypertriglyceridemia do not have FCS. A strict low-fat diet is the current first-line treatment, and existing lipid-lowering therapies are minimally effective in FCS. Apo C-III inhibitors are emerging TG-lowering therapies shown to be efficacious and safe in clinical trials. ANGPTL3 inhibitors, another class of emerging TG-lowering therapies, have been found to require at least partial lipoprotein lipase activity to lower plasma TG in clinical trials. ANGPTL3 inhibitors reduce plasma TG in patients with multifactorial chylomicronemia but not in patients with FCS who completely lack lipoprotein lipase activity.
EXPERT OPINION
Apo C-III inhibitors currently in development are promising treatments for FCS.
Topics: Humans; Hyperlipoproteinemia Type I; Angiopoietin-Like Protein 3; Apolipoprotein C-III; Hypolipidemic Agents; Lipoprotein Lipase; Angiopoietin-like Proteins; Diet, Fat-Restricted; Receptors, Lipoprotein
PubMed: 38866702
DOI: 10.1080/17446651.2024.2365787 -
Nature Genetics Jun 2024Type 2 diabetes (T2D) shows heterogeneous body mass index (BMI) sensitivity. Here, we performed stratification based on BMI to optimize predictions for BMI-related...
Type 2 diabetes (T2D) shows heterogeneous body mass index (BMI) sensitivity. Here, we performed stratification based on BMI to optimize predictions for BMI-related diseases. We obtained BMI-stratified datasets using data from more than 195,000 individuals (n = 55,284) from BioBank Japan (BBJ) and UK Biobank. T2D heritability in the low-BMI group was greater than that in the high-BMI group. Polygenic predictions of T2D toward low-BMI targets had pseudo-R values that were more than 22% higher than BMI-unstratified targets. Polygenic risk scores (PRSs) from low-BMI discovery outperformed PRSs from high BMI, while PRSs from BMI-unstratified discovery performed best. Pathway-specific PRSs demonstrated the biological contributions of pathogenic pathways. Low-BMI T2D cases showed higher rates of neuropathy and retinopathy. Combining BMI stratification and a method integrating cross-population effects, T2D predictions showed greater than 37% improvements over unstratified-matched-population prediction. We replicated findings in the Tohoku Medical Megabank (n = 26,000) and the second BBJ cohort (n = 33,096). Our findings suggest that target stratification based on existing traits can improve the polygenic prediction of heterogeneous diseases.
Topics: Humans; Diabetes Mellitus, Type 2; Multifactorial Inheritance; Body Mass Index; Genetic Predisposition to Disease; Female; Male; Genome-Wide Association Study; Biological Specimen Banks; Middle Aged; Japan; Risk Factors; Aged; Polymorphism, Single Nucleotide; United Kingdom
PubMed: 38862855
DOI: 10.1038/s41588-024-01782-y -
The American Journal of Psychiatry Jul 2024Many but not all persons with bipolar disorder require hospital care because of severe mood episodes. Likewise, some but not all patients experience long-term...
OBJECTIVE
Many but not all persons with bipolar disorder require hospital care because of severe mood episodes. Likewise, some but not all patients experience long-term occupational dysfunction that extends beyond acute mood episodes. It is not known whether these dissimilar outcomes of bipolar disorder are driven by different polygenic profiles. Here, polygenic scores (PGSs) for major psychiatric disorders and educational attainment were assessed for associations with occupational functioning and psychiatric hospital admissions in bipolar disorder.
METHODS
A total of 4,782 patients with bipolar disorder and 2,963 control subjects were genotyped and linked to Swedish national registers. Longitudinal measures from at least 10 years of registry data were used to derive percentage of years without employment, percentage of years with long-term sick leave, and mean number of psychiatric hospital admissions per year. Ordinal regression was used to test associations between outcomes and PGSs for bipolar disorder, schizophrenia, major depressive disorder, attention deficit hyperactivity disorder (ADHD), and educational attainment. Replication analyses of hospital admissions were conducted with data from the Bipolar Disorder Research Network cohort (N=4,219).
RESULTS
Long-term sick leave and unemployment in bipolar disorder were significantly associated with PGSs for schizophrenia, ADHD, major depressive disorder, and educational attainment, but not with the PGS for bipolar disorder. By contrast, the number of hospital admissions per year was associated with higher PGSs for bipolar disorder and schizophrenia, but not with the other PGSs.
CONCLUSIONS
Bipolar disorder severity (indexed by hospital admissions) was associated with a different polygenic profile than long-term occupational dysfunction. These findings have clinical implications, suggesting that mitigating occupational dysfunction requires interventions other than those deployed to prevent mood episodes.
Topics: Humans; Bipolar Disorder; Male; Female; Multifactorial Inheritance; Adult; Sweden; Sick Leave; Middle Aged; Registries; Depressive Disorder, Major; Hospitalization; Educational Status; Unemployment; Schizophrenia; Attention Deficit Disorder with Hyperactivity; Longitudinal Studies; Case-Control Studies
PubMed: 38859703
DOI: 10.1176/appi.ajp.20230073