Genetically Determined Research Articles

The “Latines Lideres En Salud (LaLiSa)” study: Rationale and design

BackgroundLatines suffer from breast cancer (BC), due to elevated biological and social determinants of health (SDOH) risks. This study compares the effects of different strategies on uptake of cancer genetic services, specifically hereditary cancer risk assessment, genetic counseling, and genetic testing, and risk-based BC care. Design/methodsIn Chicago, Illinois, Aim 1 participants are recruited from a federally qualified health center (FQHC) and community venues. For Aim 1, eligible participants: (1) are female; (2) are Latine; (3) are 30+ years old; (4) have personal or family history of BC or cancers with shared hereditary mutations; (5) have at least one SDOH risk; and (6) have not received any cancer genetic services. Participants are randomly assigned to different study arms. Both arms include phone-based sessions, FQHC-based navigation for SDOH, and low- or no-cost cancer genetic services. The educate sessions focus on risk assessment and prevention. The empower sessions focus on risk assessment and equip participants with the skills to share information about FQHC-based cancer genetic services. For Aim 2, eligible participants are: (1) female; (2) network members of Aim 1 participants; and (3) eligible for BC screening based on guidelines recommended by the American Cancer Society (ACS). Primary outcomes include uptake of any cancer genetic services. Analyses will also explore intervention differences by neighborhood context. DiscussionThis is one of the first trials focused on Latines' participation in cancer genetic services and risk-based BC care within the context of SDOH - which has major implications for equity in precision cancer prevention.

In vitro efficacy of aquaculture antimicrobials and genetic determinants of resistance in bacterial isolates from tropical aquaculture disease outbreaks.

Understanding the efficacy of antimicrobials against pathogens from clinical samples is critical for their responsible use. The manuscript presents in vitro efficacy and antimicrobial resistance (AMR) genes in seven species of fish pathogens from the disease outbreaks of Indian aquaculture against oxytetracycline, florfenicol, oxolinic acid, and enrofloxacin. In vitro efficacy was evaluated by minimum inhibitory concentration and minimum bactericidal concentration. The gene-specific PCR screened AMR genes against quinolones (qnrA, qnrB, and qnrS) and tetracyclines (tetM, tetS, tetA, tetC, tetB, tetD, tetE, tetH, tetJ, tetG, and tetY). The results showed that Aeromonas veronii (45%) showed the maximum resistance phenotype, followed by Streptococcus agalactiae (40%), Photobacterium damselae (15%), Vibrio parahaemolyticus (10%), and Vibrio vulnificus (5%). There was no resistance among Vibrio harveyi and Vibrio alginolyticus against the tested antimicrobials. The positive association between tetA, tetB, tetC, tetM, or a combination of these genes to oxytetracycline resistance and qnrS to quinolone resistance indicated their potential in surveillance studies. The prevalence of resistance phenotypes (16.43%) and evaluated AMR genes (2.65%) against aquaculture antimicrobials was low. The resistance phenotype pattern abundance was 0.143. All the isolates showed susceptibility to florfenicol. The results help with the appropriate drug selection against each species in aquaculture practices.

Genome-wide association studies of thyroid-related hormones, dysfunction, and autoimmunity among 85,421 Chinese pregnancies

Maintaining normal thyroid function is crucial in pregnancy, yet thyroid dysfunction and the presence of thyroid peroxidase antibodies (TPOAb) affect 0.5% to 18% of pregnant women. Here, we conducted a genome-wide association study (GWAS) of eight thyroid traits, including two thyroid-related hormones, four thyroid dysfunctions, and two thyroid autoimmunity measurements among 85,421 Chinese pregnant women to investigate the genetic basis of thyroid function during pregnancy. Our study identified 176 genetic loci, including 125 previously unknown genome-wide associations. Joint epidemiological and Mendelian randomization analyses revealed significant associations between the gestational thyroid phenotypes and gestational complications, birth outcomes, and later-age health outcomes. Specifically, genetically elevated thyroid-stimulating hormone (TSH) levels during pregnancy correlated with lower glycemic levels, reduced blood pressure, and longer gestational duration. Additionally, TPOAb and thyroid functions during pregnancy share genetic correlations with later-age thyroid and cardiac disorders. These findings provide insights into the genetic determinants of thyroid traits during pregnancy, which may lead to new therapeutics, early pre-diagnosis and preventive strategies starting from early adulthood.

B - 22 Self-Reported Traumatic Brain Injury and its Biopsychosocial Risk Factors in Siblings of Individuals with Neurodevelopmental Conditions

Abstract Objective Siblings of individuals with neurodevelopmental conditions (NDCs) are situated within a complex system of transdiagnostic risk and resilience factors for poor psychosocial, cognitive and behavioral outcomes. Many such factors experienced by NDC siblings overlap with risk for traumatic brain injury (TBI) and correlate with poorer recovery trajectories. Method With data from an online self-report survey, the present study used Bayesian analyses to characterize and compare TBI and biopsychosocial risk factors amongst 632 siblings (207 NDC, 425 controls; mean age 20.54 years, range 10–30, 78.48% female), and examine correlations between clinical, biological, and social determinant of health variables. Results NDC siblings had a higher self-reported lifetime history of TBI compared to controls (14.98% versus 6.35%), with most NDC siblings reporting more than one TBI, and at an earlier mean age. TBI history was associated with psychiatric diagnoses and subclinical NDC features, including hyperactivity and impulsivity, inattention, conduct problems, and autistic traits. Family and structural factors related to TBI included poorer parent–child relationship, NDC diagnoses of autism or fetal alcohol spectrum disorder, minority ethnicity and lower income. Conclusions Findings have important clinical and policy implications for health literacy, TBI education and screening, development of prevention and intervention strategies, and implementation of family support to target social and structural determinants of health impacting NDC sibling wellbeing.

Revealing genetic causality between blood-based biomarkers and major depression in east Asian ancestry.

Major Depression (MD) is a common mental disorder. In East Asian ancestry, the association, causality, and shared genetic basis between blood-based biomarkers and MD remain unclear. We investigated the relationships between blood-based biomarkers and MD through a cross-sectional study and Mendelian randomization (MR) analysis. Cross-trait analysis and enrichment analyses were used to highlight the shared genetic determinants and biological pathways. We conducted summary data-based MR to identify shared genes, which were then validated using a transcriptome dataset from drug-naïve patients with MD. In the cross-sectional study, C-Reactive Protein showed the significantly positive correlation with depressive symptoms, while hematocrit, hemoglobin, and uric acid exhibited significantly negative correlations. In MR analysis, basophil count (BASO) and low-density lipoprotein cholesterol (LDLc) had a significant causal effect on MD. The enrichment analysis indicated a significant role of inflammatory cytokines and oxidative stress. The shared genes MFN2, FAM55C, GCC2, and SCAPER were validated, with MFN2 identified as a pleiotropic gene involved in MD, BASO, and LDLc. This study highlighted that BASO and LDLc have a causal effect on MD in East Asian ancestry. The pathological mechanisms of MD are related not only to inflammatory cytokines and oxidative stress but also to down regulation of MFN2 expression and mitochondrial dysfunction.

Identification of the genetic determinants of shovel-shaped incisors and Carabelli’s cusp

Shovel-shaped incisors (SSI) and Carabelli’s cusp (CC) are noteworthy human dental non-metric traits which presence and degree of expression have been reported to cluster within distinct populations. Recent advances in developmental biology suggest that SSI and CC are likely under polygenic developmental control; therefore, genetic variation in multiple genes is likely to contribute to differential SSI and CC expression. The exact genetic mechanisms underlying variation in SSI and CC development, however, remain mostly unknown. This study aims to identify whether variation in the basal DNA sequences of six candidate genes, NKX2-3, SOSTDC1, BMP4, FGF3, FGF4, and WNT10A, has any impact on SSI and/or CC expression. Study methods involve collection of saliva samples and dental data from 36 participants. The Arizona State University Dental Anthropology System (ASUDAS) has been used to score SSI and CC expression. Next-generation sequencing (NGS) methods were utilized to sequence the entire gene region of the candidate genes. Spearman’s correlation test was used to score the relationship between the genotype and degree of trait expression of participants. Fifteen SNPs/INDELs belonging to SOSTDC1, FGF3, FGF4 and WNT10A were significantly associated with SSI and/or CC expression. No SNPs/INDELs were detected in the genes BMP4 and NKX2-3 that significantly contributes to observed phenotypes. FGF3, FGF4, SOSTDC1 and WNT10A were possibly involved in the formation of shoveling and Carabelli’s cusp. However, because of the small sample size, more studies are needed to confirm their role and rule out any potential role of NKX2-3 and BMP4 in the production of SSI and CC.

Lack of a genetic risk continuum between pubertal timing in the general population and idiopathic hypogonadotropic hypogonadism.

Pubertal timing is a highly heritable trait in the general population. Recently, a large-scale exome-wide association study has implicated rare variants in six genes (KDM4C, MC3R, MKRN3, PDE10A, TACR3, and ZNF483) as genetic determinants of pubertal timing within the general population. Two of the genes (TACR3, MKRN3) are already implicated in extreme disorders of pubertal timing. This observation suggests that there may be a pervasive "genetic risk continuum" wherein genes that govern pubertal timing in the general population, by extension, may also be causal for rare Mendelian disorders of pubertal timing. Hence, we hypothesized that the four novel genes linked to pubertal timing in the population will also contribute to idiopathic hypogonadotropic hypogonadism (IHH), a genetic disorder characterized by absent puberty. Exome sequencing data from 1322 unrelated IHH probands were reviewed for rare sequence variants (RSVs) (minor allele frequency bins: <1%; <0.1%; <0.01%) in the six genes linked to puberty in the general population. A gene-based rare variant association testing (RVAT) was performed between the IHH cohort and a reference public genomic sequences repository-the Genome Aggregation Database (gnomAD). As expected, RVAT analysis showed that RSVs in TACR3, a known IHH gene, were significantly enriched in the IHH cohort compared to gnomAD cohort across all three MAF bins. However, RVAT analysis of the remaining five genes failed to show any RSV enrichment in the IHH cohort across all MAF bins. Our findings argue strongly against a pervasive genetic risk continuum between pubertal timing in the general population and extreme pubertal phenotypes. The biologic basis of such distinct genetic architectures' merits further evaluation.

Genomic insights into mRNA COVID-19 vaccines efficacy: Linking genetic polymorphisms to waning immunity

ABSTRACT Genetic polymorphisms have been linked to the differential waning of vaccine-induced immunity against COVID-19 following vaccination. Despite this, evidence on the mechanisms behind this waning and its implications for vaccination policy remains limited. We hypothesize that specific gene variants may modulate the development of vaccine-initiated immunity, leading to impaired immune function. This study investigates genetic determinants influencing the sustainability of immunity post-mRNA vaccination through a genome-wide association study (GWAS). Utilizing a hospital-based, test negative case-control design, we enrolled 1,119 participants from the Taiwan Precision Medicine Initiative (TPMI) cohort, all of whom completed a full mRNA COVID-19 vaccination regimen and underwent PCR testing during the Omicron outbreak. Participants were classified into breakthrough and protected groups based on PCR results. Genetic samples were analyzed using SNP arrays with rigorous quality control. Cox regression identified significant single nucleotide polymorphisms (SNPs) associated with breakthrough infections, affecting 743 genes involved in processes such as antigenic protein translation, B cell activation, and T cell function. Key genes identified include CD247, TRPV1, MYH9, CCL16, and RPTOR, which are vital for immune responses. Polygenic risk score (PRS) analysis revealed that individuals with higher PRS are at greater risk of breakthrough infections post-vaccination, demonstrating a high predictability (AUC = 0.787) in validating population. This finding confirms the significant influence of genetic variations on the durability of immune responses and vaccine effectiveness. This study highlights the importance of considering genetic polymorphisms in evaluating vaccine-induced immunity and proposes potential personalized vaccination strategies by tailoring regimens to individual genetic profiles.

Pathophysiology and Treatment of Prediabetes and Type 2 Diabetes in Youth.

Youth-onset type 2 diabetes is a heterogeneous disease with increasing prevalence in relation to increased rates of obesity in children. It has genetic, epigenetic, social, and environmental determinants. Youth-onset type 2 diabetes is alarming given a rapidly progressive course compared with the course of adult-onset disease, early-onset vascular complications, and long-term exposure to hyperglycemia and associated complications. It is often preceded by "prediabetes," a disease phase where defects in β-cell function relative to insulin sensitivity emerge. Herein, we review the current understanding of the pathophysiology of prediabetes and type 2 diabetes in youth. We describe the mechanisms underlying insulin resistance, the precipitous decline of β-cell function, and the role of other hormonal abnormalities in the pathogenesis of the disease. We discuss the critical importance of social determinants of health in the predisposition and progression of these conditions and present current management strategies and the advances in therapeutic approaches. These must adapt to meet the unique needs of the individual patient and family. Significant knowledge gaps remain that need to be addressed in future research.

Evolutionary dynamics in gut-colonizing Candida glabrata during caspofungin therapy: Emergence of clinically important mutations in sphingolipid biosynthesis.

Invasive fungal infections are associated with high mortality, which is exacerbated by the limited antifungal drug armamentarium and increasing antifungal drug resistance. Echinocandins are a frontline antifungal drug class targeting β-glucan synthase (GS), a fungal cell wall biosynthetic enzyme. Echinocandin resistance is generally low but increasing in species like Candida glabrata, an opportunistic yeast pathogen colonizing human mucosal surfaces. Mutations in GS-encoding genes (FKS1 and FKS2 in C. glabrata) are strongly associated with clinical echinocandin failure, but epidemiological studies show that other, as yet unidentified factors also influence echinocandin susceptibility. Furthermore, although the gut is known to be an important reservoir for emergence of drug-resistant strains, the evolution of resistance is not well understood. Here, we studied the evolutionary dynamics of C. glabrata colonizing the gut of immunocompetent mice during treatment with caspofungin, a widely-used echinocandin. Whole genome and amplicon sequencing revealed rapid genetic diversification of this C. glabrata population during treatment and the emergence of both drug target (FKS2) and non-drug target mutations, the latter predominantly in the FEN1 gene encoding a fatty acid elongase functioning in sphingolipid biosynthesis. The fen1 mutants displayed high fitness in the gut specifically during caspofungin treatment and contained high levels of phytosphingosine, whereas genetic depletion of phytosphingosine by deletion of YPC1 gene hypersensitized the wild type strain to caspofungin and was epistatic to fen1Δ. Furthermore, high resolution imaging and mass spectrometry showed that reduced caspofungin susceptibility in fen1Δ cells was associated with reduced caspofungin binding to the plasma membrane. Finally, we identified several different fen1 mutations in clinical C. glabrata isolates, which phenocopied the fen1Δ mutant, causing reduced caspofungin susceptibility. These studies reveal new genetic and molecular determinants of clinical caspofungin susceptibility and illuminate the dynamic evolution of drug target and non-drug target mutations reducing echinocandin efficacy in patients colonized with C. glabrata.

Biological and ecological determinants of Hand Foot and Mouth Disease (HFMD) in Coastal District of Northeastern Peninsular Malaysia: A 5-Year retrospective study

Hand, foot, and mouth disease (HFMD) is a common viral communicable disease in Malaysia, characterized by its self-limiting nature, yet it leads to numerous outbreaks and fatalities, particularly among young children. The current study aimed to determine the prevalence, geographic distribution, temporal patterns, and associated factors of HFMD cases within the Bachok District of Kelantan, spanning the years 2018 to 2022. A retrospective cohort study analysed extract data on independent factors and notification status from the Communicable Disease Control Information System (CDCIS). Simple and multiple logistic regression analyses were employed on a cohort of 1351 HFMD’s notifications. The retrospective analysis reveals a predominant HFMD’s notification were males (56.7%). Outpatient care was common (98.4%), with primary health care being the main choice. Logistic regression indicates higher odds for HFMD in those attending primary health care or private practitioners, daycare attendees, during the Southwest Monsoon season, and before the Movement Control Order (MCO) implementation, emphasizing key risk factors for HFMD. This study’s integrative approach recognizes that health and disease are often influenced by a combination of factors spanning the ecological, biological, and clinical domains. Thus, emphasizing the need for a comprehensive understanding when formulating public health strategies particularly in primary healthcare settings and daycare facilities during the Southwest Monsoon season.

A plasmid-mediated type III secretion system associated with invasiveness and diarrheagenicity of Providencia rustigianii.

We have recently described a clinical isolate of Providencia rustigianii strain JH-1 carrying the genes for cytolethal distending toxin (CDT) in a conjugative plasmid. A cdtB mutant of strain JH-1, which lost CDT activity, was still found to retain invasiveness and diarrheagenicity. The strain was subjected to phenotypic and genetic analyses including whole genome sequencing (WGS) to explore the genetic determinants of the observed invasiveness and diarrheagenic properties. Analysis and annotation of WGS data revealed the presence of two distinct type III secretion systems (T3SS) in strain JH-1, one of which was located on the chromosome designated as cT3SS (3,992,833 bp) and the other on a mega-plasmid designated as pT3SS (168,819 bp). Comparative genomic analysis revealed that cT3SS is generally conserved in Providencia spp. but pT3SS was limited to a subset of Providencia spp., carrying cdt genes. Strain JH-1 was found to invade HeLa cells and induce fluid accumulation with characteristic pathological lesions in rabbit ileal loops. Remarkably, these phenomena were associated with the pT3SS but not cT3SS. The plasmid could be transferred by conjugation from strain JH-1 to other strains of P. rustigianii, Providencia rettgeri, and Escherichia coli with concomitant transfer of these virulence properties. This is the first report of a functional and mobile T3SS in P. rustigianii and its association with invasiveness and diarrheagenicity of this bacterium. These data suggest that P. rustigianii and other CDT-producing Providencia strains might carry T3SS and exert their diarrheagenic effect by exploiting the T3SS nano-machinery.IMPORTANCEThe precise mechanism of virulence of Providencia rustigianii is unclear, although some strains produce cytolethal distending toxin as a putative virulence factor. We have detected the presence of a type III secretion system (T3SS) for the first time on a plasmid in a P. rustigianii strain. Plasmid-mediated T3SS seems to be directly involved in virulence of P. rustigianii and may serve as a means of horizontal transfer of T3SS genes. Our results may have implication in understanding the mechanism of emergence of new pathogenic strains of P. rustigianii.

Characteristics of the Klebsiella Pneumoniae Strain Isolated from a Positive Blood Culture of a Premature Newborn Baby According to the Results of Whole Genome Sequencing

Relevance. K. pneumoniae is a common nosocomial pathogen in pediatric hospitals, often characterized by the presence of a wide range of virulence factors and genetic determinants of antibiotic resistance. Аim. To analyze the results obtained during wholegenome sequencing of a Klebsiella pneumoniae strain isolated from a positive blood culture of a premature newborn. Materials and methods. An ESBL-producing strain of K. pneumoniae isolated from a positive blood culture of a newborn premature infant. Sequencing was performed on the MiSeq platform (Illumina). Analysis of DNA nucleotide sequences of the complete genome of K. pneumoniae was carried out using the website of the Center for Genomic Epidemiology. The search for genetic determinants of antibiotic resistance and virulence was carried out using online services. Results and its discussion. The resulting nucleotide sequence was 5,414,099 bp in length, and the proportion of GC nitrogenous bases was 57.3%. The isolated strain belonged to the sequence type ST3559, had 4 genes encoding the synthesis of enzymes that hydrolyze antibacterial drugs from the beta-lactam group, 2 genes providing resistance to quinolones/fluoroquinolones, 1 resistance gene each to trimethoprim, chloramphenicol, fosfomycin and aminoglycoside antibiotics. Most of the virulence factor genes identified in the studied strain ensure the recognition and absorption of iron ions necessary for the competitive functioning of the bacterial cell. K. pneumoniae possesses the acrA efflux pump gene and its regulators, as well as 4 prophage particles and 1 CRISPCas IE system. Conclusions. Whole-genome sequencing of the K. pneumoniae strain isolated from a positive blood culture of a premature newborn allows us to characterize in detail the causative agent of a generalized infection and detect a wide range of genetic determinants of virulence factors and antibiotic resistance. The ESBL-producing strain of K. pneumoniae, as the etiological agent of neonatal sepsis, was characterized by the presence of virulence genes, multidrug resistance, both due to genes encoding enzymes that hydrolyze antibiotics, and due to the presence of efflux pumps and their regulators. The use of the results of traditional cultural research methods together with high-throughput sequencing data is a promising area of scientific research and has a reserve of practical application in the field of clinical medicine, genetics of microorganisms, molecular epidemiology at the local and global levels

Exploring genetic determinants of silver oxide nanoparticle-induced seed priming for drought tolerance in wheat

Exploring genetic determinants of silver oxide nanoparticle-induced seed priming for drought tolerance in wheat

VUS next in rare diseases? Deciphering genetic determinants of biomolecular condensation

The diagnostic odysseys for rare disease patients are getting shorter as next-generation sequencing becomes more widespread. However, the complex genetic diversity and factors influencing expressivity continue to challenge accurate diagnosis, leaving more than 50% of genetic variants categorized as variants of uncertain significance.Genomic expression intricately hinges on localized interactions among its products. Conventional variant prioritization, biased towards known disease genes and the structure-function paradigm, overlooks the potential impact of variants shaping the composition, location, size, and properties of biomolecular condensates, genuine membraneless organelles swiftly sensing and responding to environmental changes, and modulating expressivity.To address this complexity, we propose to focus on the nexus of genetic variants within biomolecular condensates determinants. Scrutinizing variant effects in these membraneless organelles could refine prioritization, enhance diagnostics, and unveil the molecular underpinnings of rare diseases. Integrating comprehensive genome sequencing, transcriptomics, and computational models can unravel variant pathogenicity and disease mechanisms, enabling precision medicine. This paper presents the rationale driving our proposal and describes a protocol to implement this approach. By fusing state-of-the-art knowledge and methodologies into the clinical practice, we aim to redefine rare diseases diagnosis, leveraging the power of scientific advancement for more informed medical decisions.

Genetic determinants of age at menarche: does the LIN28B gene play a role? A narrative review.

Menarche, the first menstrual period marking the onset of female reproduction, is a milestone of female puberty. The timing of menarche determines the timing of later phases of pubertal maturation in girls and has major implications for health later in life, including behavioral and psychosocial disorders during adolescence and fertility problems and increased risk for certain diseases in adulthood. Over the last few decades, a continuous decline in age at menarche has been noted, with environmental factors contributing to this change in the timing of menarche. However, a genetic component of age at menarche and pubertal onset has been strongly suggested by studies in families and twins wherein up to approximately 80% of the variance in puberty onset can be explained by heritability. Gene association studies have revealed several genetic loci involved in age at menarche, among which LIN28B has emerged as a key regulator of female growth and puberty. LIN28B, a human homolog of Lin28 of C. elegans, is a known RNA-binding protein that regulates let-7 microRNA biogenesis. Genome-wide association studies have identified the association of polymorphisms in the LIN28B gene with age at menarche in several population cohorts worldwide. In this paper, we review the genetic factors contributing to age of menarche, with particular focus on the identified polymorphisms in LIN28B gene.

A Social Constructionist Critique of Genetic Determinism

ABSTRACTRecently genetic determinist claims have reappeared in the explanation of human psychology and to some extent they even made their way into explanations of social phenomena. In this article, I will provide a critical analysis of the genetic determinist discourse from a social constructionist perspective. First, I will examine the meaning of genetic determinism. Then I will shortly introduce the social constructionist perspective generally and it's relevance for analyzing scientific discourses. Next, I will examine the debates about genetic determinism in behavior genetics and sociogenomics and interpret these critically from a social constructionist and deconstructionist perspective. Finally, I will provide an analysis of the main social, ideological, cultural and economic factors that influence the development of genetic determinist ideas: modernity, the legitimation of social hierarchies, neoliberalism and business interests. My conclusion is that the social constructionist perspective is important in the analysis and critique of the genetic determinist discourse.

Multi-omic lineage tracing predicts the transcriptional, epigenetic and genetic determinants of cancer evolution

Cancer is a highly heterogeneous disease, where phenotypically distinct subpopulations coexist and can be primed to different fates. Both genetic and epigenetic factors may drive cancer evolution, however little is known about whether and how such a process is pre-encoded in cancer clones. Using single-cell multi-omic lineage tracing and phenotypic assays, we investigate the predictive features of either tumour initiation or drug tolerance within the same cancer population. Clones primed to tumour initiation in vivo display two distinct transcriptional states at baseline. Remarkably, these states share a distinctive DNA accessibility profile, highlighting an epigenetic basis for tumour initiation. The drug tolerant niche is also largely pre-encoded, but only partially overlaps the tumour-initiating one and evolves following two genetically and transcriptionally distinct trajectories. Our study highlights coexisting genetic, epigenetic and transcriptional determinants of cancer evolution, unravelling the molecular complexity of pre-encoded tumour phenotypes.

Genetic and environmental determinants of Immunoglobulin G in kid serum and adult colostrum of dairy goats

Immune competence is a key factor in the health and resilience of dairy ruminants. The aim of this study was to study immunoglobulin G concentration in serum shortly after birth and in colostrum of lactating animals as proxy of passive immune transfer and colostrum quality, respectively, and thus provide new health and resilience indicators for selection. Data from 424 female kids and 203 primiparous goats, reared on an INRAE experimental farm, were analyzed. IgG concentration was measured in kid serum and goat colostrum, respectively, using the radial immunodiffusion technique. Linear models were used to identify factors of variation in serum and colostrum IgG concentration, and health events were monitored for 5 weeks after birth to measure the impact of passive immune transfer on kids' health. We found a significant effect of serum IgG level on hindquarters cleanliness score (as a proxy of digestive troubles) and nasal and ocular discharge. As expected, the absorption of IgG in the days following birth is essential to ensure the passive transfer of immunity from the mother to the youngster, and provide immune protection. Genetic parameters were estimated for serum IgG concentration in kids and for colostrum characteristics in primiparous goats. Heritability of serum IgG in kids was not significantly different from zero. This low value, with large SE, may be due to the limited sample size and large environmental variability likely not accounted for. Especially, we could not adjust for the amount of IgG that was ingested by the kid, which can have a significant effect on serum IgG and possibly on heritability estimates. Heritability of colostrum traits were moderate, with estimates of 0.25 (±0.16), 0.35 (±0.16), and 0.25 (±0.16) for IgG concentration, IgG mass and colostrum volume, respectively. Genetic correlations with milk production showed high standard errors due to small numbers. However, estimates suggest a negative genetic association between production and IgG concentration in colostrum (rg = -0.44 ± 0.33), probably linked to a positive association with total colostrum volume. The significant heritabilities that were estimated for the first time demonstrate the existence of genetic control of colostrum quality in goats, and open up opportunities for selection in this species.

P030 EFFECTS OF GENDER-RELATED FACTORS ON THE HYPERTENSION-WHITE MATTER HYPERINTENSITIES ASSOCIATION: A SEX-STRATIFIED ANALYSIS

Background: Hypertension (HTN) is a global health issue affecting various vascular beds, including the brain. There is a gap in understanding how gender-related factors, such as roles, identity, relationships, and institutionalized gender, contribute to sex differences in the relationship between HTN and brain structure changes. This study aims to investigate the role of gender-related factors in the relationship between HTN and white matter hyperintensities (WMH) in both males and females. Methods: This cohort study used MRI data from 41,300 UK Biobank participants. HTN status was determined through hospital records and self-report, and WMH volumes were measured using MRI. Eight gender-related factors, including unpaid work, caregiving, unemployment, risk-taking behavior, living alone, education, income, and material deprivation, were examined. Generalized linear models were used to evaluate the interactions between each gender-related factor and HTN in males and females. Effect modification was evaluated using the Z-test to compare the beta coefficients of the HTN-WMH association across strata. Results: The study included 19,260 males and 22,040 females aged 40-69 years at baseline, with 27.3% hypertensive. Hypertensive males (7.7±9.2 mL) and females (7.2±8.8 mL) exhibited greater WMH volumes compared to their normotensive counterparts (males: 4.7±5.9 mL; females: 3.9±5.2 mL). The main effects model revealed that low income was significantly associated with greater WMHs in females, while no gender-related factors were linked to WMHs in males after adjusting for clinical, behavioral, and gender-related variables. No significant interactions between HTN and gender-related factors were found in either males or females after adjustment. In the stratified analysis, females with lower material deprivation showed a significantly greater increase in WMHs compared to those with higher material deprivation. No other gender-related factors in either group interacted with HTN to amplify the association with WMHs. Discussion: Socioeconomic factors, particularly in females, were associated with WMH. These findings highlight the importance of considering biological and social determinants to address hypertension risks effectively.