DNA methylation may partly explain psychotropic drug-induced metabolic side effects: results from a prospective 1-month observational study.

BACKGROUND: Metabolic side effects of psychotropic medications are a major drawback to patients' successful treatment. Using an epigenome-wide approach, we aimed to investigate DNA methylation changes occurring secondary to psychotropic treatment and evaluate associations between 1-month metabolic changes and both baseline and 1-month changes in DNA methylation levels. Seventy-nine patients starting a weight gain inducing psychotropic treatment were selected from the PsyMetab study cohort. Epigenome-wide DNA methylation was measured at baseline and after 1 month of treatment, using the Illumina Methylation EPIC BeadChip. RESULTS: A global methylation increase was noted after the first month of treatment, which was more pronounced (p < 2.2 × 10-16) in patients whose weight remained stable (< 2.5% weight increase). Epigenome-wide significant methylation changes (p < 9 × 10-8) were observed at 52 loci in the whole cohort. When restricting the analysis to patients who underwent important early weight gain (≥ 5% weight increase), one locus (cg12209987) showed a significant increase in methylation levels (p = 3.8 × 10-8), which was also associated with increased weight gain in the whole cohort (p = 0.004). Epigenome-wide association analyses failed to identify a significant link between metabolic changes and methylation data. Nevertheless, among the strongest associations, a potential causal effect of the baseline methylation level of cg11622362 on glycemia was revealed by a two-sample Mendelian randomization analysis (n = 3841 for instrument-exposure association; n = 314,916 for instrument-outcome association). CONCLUSION: These findings provide new insights into the mechanisms of psychotropic drug-induced weight gain, revealing important epigenetic alterations upon treatment, some of which may play a mediatory role.

Genetic risk score for gestational weight gain.

Gestational weight gain (GWG) involves health consequences for both mother and offspring. Genetic factors seem to play a role in the GWG trait. For small effect sizes of a single genetic polymorphism (SNP), a genetic risk score (GRS) summarizing risk-associated variation from multiple SNPs can serve as an effective approach to genetic association analysis. The aim of the study was to analyze the association between genetic risk score (GRS) and gestational weight gain (GWG). GWG was calculated for a total of 342 healthy Polish women of Caucasian origin, aged 19 to 45 years. The SNPs rs9939609 (FTO), rs6548238 (TMEM18), rs17782313 (MC4R), rs10938397 (GNPDA2), rs10913469 (SEC16B), rs1137101 (LEPR), rs7799039 (LEP), and rs5443 (GNB3) were genotyped using commercial TaqMan SNP assays. A simple genetic risk score was calculated into two ways: GRS1 based on the sum of risk alleles from each of the SNPs, while GRS2 based on the sum of risk alleles of FTO, LEPR, LEP, and GNB3. Positive association between GRS2 and GWG (ß = 0.12, p = 0.029) was observed. Genetic risk variants of TMEM18 (p = 0.006, OR = 2.6) and GNB3 (p < 0.001, OR = 3.3) are more frequent in women with increased GWG, but a risk variant of GNPDA2 (p < 0.001, OR = 2.7) is more frequent in women with adequate GWG, and a risk variant of LEPR (p = 0.011, OR = 3.1) in women with decreased GWG. GRS2 and genetic variants of TMEM18, GNB3, GNPDA2, and LEPR are associated with weight gain during pregnancy.

A transcriptomic analysis of skeletal muscle tissues reveals promising candidate genes and pathways accountable for different daily weight gain in Hanwoo cattle.

Cattle traits like average daily weight gain (ADG) greatly impact profitability. Selecting based on ADG considering genetic variability can lead to economic and genetic advancements in cattle breeding. This study aimed to unravel genetic influences on ADG variation in Hanwoo cattle at the skeletal muscle transcriptomic level. RNA sequencing was conducted on longissimus dorsi (LD), semimembranosus (SB), and psoas major (PM) muscles of 14 steers assigned to same feed, grouped by low (≤ 0.71 kg) and high (≥ 0.77 kg) ADG. At P ≤ 0.05 and log2fold > 1.5, the distinct pattern of gene expression was identified with 184, 172, and 210 differentially expressed genes in LD, SB, and PM muscles, respectively. Tissue-specific responses to ADG variation were evident, with myogenesis and differentiation associated JAK-STAT signaling pathway and prolactin signaling pathways enriched in LD and SB muscles, while adipogenesis-related PPAR signaling pathways were enriched in PM muscle. Key hub genes (AXIN2, CDKN1A, MYC, PTGS2, FZD5, SPP1) were upregulated and functionally significant in muscle growth and differentiation. Notably, DPP6, CDKN1A, and FZD5 emerged as possible candidate genes linked to ADG variation. These findings enhance our understanding of genetic factors behind ADG variation in Hanwoo cattle, illuminating skeletal muscle mechanisms influencing ADG.

Pharmacogenetics of weight gain following switch from efavirenz- to integrase inhibitor-containing regimens.

BACKGROUND: Excessive weight gain affects some persons with HIV after switching to integrase strand transfer inhibitor (INSTI)-containing antiretroviral therapy (ART). We studied associations between CYP2B6 genotype and weight gain after ART switch among ACTG A5001 and A5322 participants. METHODS: Eligible participants switched from efavirenz- to INSTI-containing ART, had genotype data, and had weight data at least once from 4 weeks to 2 years post-switch. Multivariable linear mixed effects models adjusted for race/ethnicity, CD4, age, BMI and INSTI type assessed relationships between CYP2B6 genotype and estimated differences in weight change. RESULTS: A total of 159 eligible participants switched ART from 2007 to 2019, of whom 138 had plasma HIV-1 RNA < 200 copies/mL (65 CYP2B6 normal, 56 intermediate, 17 poor metabolizers). Among participants with switch HIV-1 RNA < 200 copies/mL, weight increased in all 3 CYP2B6 groups. The rate of weight gain was greater in CYP2B6 poor than in CYP2B6 normal metabolizers overall, and within 9 subgroups (male, female, White, Black, Hispanic, dolutegravir, elvitegravir, raltegravir, and TDF in the pre-switch regimen); only in Hispanic and elvitegravir subgroups were these associations statistically significant ( P  < 0.05). Compared to normal metabolizers, CYP2B6 intermediate status was not consistently associated with weight gain. CONCLUSION: CYP2B6 poor metabolizer genotype was associated with greater weight gain after switch from efavirenz- to INSTI-containing ART, but results were inconsistent. Weight gain in this setting is likely complex and multifactorial.

Association of clinical parameters and polygenic risk scores for body mass index, schizophrenia, and diabetes with antipsychotic-induced weight gain.

Antipsychotic-induced weight gain (AIWG) is a common adverse event in schizophrenia. Genome-wide association studies (GWAS) and polygenic risk scores (PRS) for other diseases or traits are recent approaches to disentangling the genetic architecture of AIWG. 200 patients with schizophrenia treated monotherapeutically with antipsychotics were included in this study. A multiple linear regression analysis with ten-fold crossvalidation was performed to predict the percentage weight change after five weeks of treatment. Independent variables were sex, age, body mass index (BMI) at baseline, medication-associated risk, and PRSs (BMI, schizophrenia, diabetes, and metabolic syndrome). An explorative GWAS analysis was performed on the same subjects and traits. PRSs for BMI (ß = 3.78; p = 0.0041), schizophrenia (ß = 5.38; p = 0.021) and diabetes type 2 (ß = 13.4; p = 0.046) were significantly associated with AIWG. Other significant factors were sex, baseline BMI and medication. Compared to the model without genetic factors, the addition of PRSs for BMI, schizophrenia, and diabetes type 2 increased the goodness of fit by 6.5 %. The GWAS identified the association of three variants (rs10668573, rs10249381 and rs1988834) with AIWG at a genome-wide level of p < 1 · 10-6. Using PRS for schizophrenia, BMI, and diabetes type 2 increased the explained variation of predicted weight gain, compared to a model without PRSs. For more precise results, PRSs derived from other traits (ideally AIWG) should be investigated. Potential risk variants identified in our GWAS need to be further investigated and replicated in independent samples.

Genome-wide association study for body weight and feed consumption traits in Japanese quail using Bayesian approaches.

The aim of this study was to perform a genome-wide association study (GWAS) based on Bayes A and Bayes B statistical methods to identify genomic loci and candidate genes associated with body weight gain, feed intake, and feed conversion ratio in Japanese quail. For this purpose, genomic data obtained from Illumina iSelect 4K quail SNP chip were utilized. After implementing various quality control steps, genotype data from a total of 875 birds for 2,015 SNP markers were used for subsequent analyses. The Bayesian analyses were performed using hibayes package in R (version 4.3.1) and Gibbs sampling algorithm. The results of the analyses showed that Bayes A accounted for 11.43, 11.65, and 11.39% of the phenotypic variance for body weight gain, feed intake, and feed conversion ratio, respectively, while the variance explained by Bayes B was 7.02, 8.61, and 6.48%, respectively. Therefore, in the current study, results obtained from Bayes A were used for further analyses. In order to perform the gene enrichment analysis and to identify the functional pathways and classes of genes that are over-represented in a large set of genes associated with each trait, all markers that accounted for more than 0.1% of the phenotypic variance for each trait were used. The results of this analysis revealed a total of 23, 38, and 14 SNP markers associated with body weight gain, feed intake, and feed conversion ratio in Japanese quail, respectively. The results of the gene enrichment analysis led to the identification of biological pathways (and candidate genes) related to lipid phosphorylation (TTC7A gene) and cell junction (FGFR4 and FLRT2 genes) associated with body weight gain, calcium signaling pathway (ADCY2 and CAMK1D genes) associated with feed intake, and glycerolipid metabolic process (LIPC gene), lipid metabolic process (ADGRF5 and ESR1 genes), and glutathione transferase (GSTK1 gene) associated with feed conversion ratio. Overall, the findings of this study can provide valuable insights into the genetic architecture of growth and feed consumption traits in Japanese quail.

Characterization of metabolic phenotypes and distinctive genes in mice with low-weight gain.

Being overweight exacerbates various metabolic diseases, necessitating the identification of target molecules for obesity control. In the current study, we investigated common physiological features related to metabolism in mice with low weight gain: (1) G protein-coupled receptor, family C, group 5, member B-knockout; (2) gastric inhibitory polypeptide receptor-knockout; and (3) Iroquois-related homeobox 3-knockout. Moreover, we explored genes involved in metabolism by analyzing differentially expressed genes (DEGs) between low-weight gain mice and the respective wild-type control mice. The common characteristics of the low-weight gain mice were low inguinal white adipose tissue (iWAT) and liver weight despite similar food intake along with lower blood leptin levels and high energy expenditure. The DEGs of iWAT, epididymal (gonadal) WAT, brown adipose tissue, muscle, liver, hypothalamus, and hippocampus common to these low-weight gain mice were designated as candidate genes associated with metabolism. One such gene tetraspanin 7 (Tspan7) from the iWAT was validated using knockout and overexpressing mouse models. Mice with low Tspan7 expression gained more weight, while those with high Tspan7 expression gained less weight, confirming the involvement of the Tspan7 gene in weight regulation. Collectively, these findings suggest that the candidate gene list generated in this study contains potential target molecules for obesity regulation. Further validation and additional data from low-weight gain mice will aid in understanding the molecular mechanisms associated with obesity.

Estimation of genetic parameters for weight and length gains in tambaqui (Colossoma macropomum).

The goal of this study was to determine the genetic parameters for growth traits in tambaqui (Colossoma macropomum) fish of similar age and weight. The data set included monthly measurements of body weight and length from120 fish for a year (1,440 measurements). The study found that weight gain had a heritability estimate of 0.01, while length gain had a heritability estimate of 0.27. There was a high positive correlation (0.84) between weight and length gains. The genetic variance and heritability of body weight decreased with age. This study suggests that breeding programs should select for body weight and weight gain to promote genetic gain in tambaqui. Selecting younger animals can also help reduce costs while still achieving genetic gains.

Performance, carcass characteristics and non-carcass components of Santa Ines and crossbred (Santa Ines x Dorper) lambs finished in different confinement strategies.

Genetic group, age at entry into confinement and at slaughter, are characteristics that have an important influence on lamb performance and carcass. The aim of this study was to evaluate the performance, carcass characteristics and non-carcass components from different genetic groups (Santa Inês and ½ Dorper x ½ Santa Inês) sheep, submitted to different feedlot entry and exit strategies. Were used 72 lambs males and castrated; 36 Santa Inês (SI) and 36 crossbred (Dorper x Santa Inês-DSI), with 6 months of average initial age. The groups were established in a completely randomized experimental design, in a 2x3x4 factorial arrangement, from the combination of genetic groups (GG), body weight at the beginning of confinement (WBC) and length of stay in confinement (LSC). The body weight classes at the beginning of confinement were: light (25 kg), intermediate (28 kg) and heavy (31 kg), for Santa Inês and crossbreeds, respectively. Slaughters were carried out every 28 days of confinement, in four LSC: 0, 28, 56 and 84 days. The GG did not influence performance, carcass and non-carcass component traits of lambs (p > 0.05). There was an effect of the WBC on the weights: final (FW), metabolic (MW), body at slaughter (BWS), empty body (EBW), hot carcass (HCY) and cold (CCW), loin, shoulder, leg musculature; loin eye area (LEA) and loin fat (p < 0.05). There was also an effect on LSC, for FW, average daily weight gain (ADG), MW, weight and yield of body components, weight of cuts and tissue ratio components of cuts (p < 0.05). In non-carcass components, effect on full and empty weight of: omasum, rumen-reticulum, small intestine; empty large intestine, liver and kidneys, paws and skin, and perirenal, pelvic and inguinal fat (p < 0.05). Interaction double effect on the tissue muscle/fat:bone ratio (MF:B) and for the full omasal component (p < 0.05). And triple interaction effect for ADG, full omasum and perirenal fat (p < 0.05). Weight at the beginning of confinement and confinement time are the characteristics that most influence performance, quantitative characteristics of carcass and non-carcass components. Regardless of the genetic group and age class, the animals reach the same weight after 84 days of confinement. Thus, the confinement of heavier lambs (31 kg) can be a profitable alternative, as they presented the highest weights for the most commercially valued cuts (shank and loin). The confinement strategy must adapt to market situations.

Disentangling the dynamics of energy allocation to develop a proxy for robustness of fattening pigs.

BACKGROUND: There is a growing need to improve robustness of fattening pigs, but this trait is difficult to phenotype. Our first objective was to develop a proxy for robustness of fattening pigs by modelling the longitudinal energy allocation coefficient to growth, with the resulting environmental variance of this allocation coefficient considered as a proxy for robustness. The second objective was to estimate its genetic parameters and correlations with traits under selection and with phenotypes that are routinely collected. In total, 5848 pigs from a Pietrain NN paternal line were tested at the AXIOM boar testing station (Azay-sur-Indre, France) from 2015 to 2022. This farm is equipped with an automatic feeding system that records individual weight and feed intake at each visit. We used a dynamic linear regression model to characterize the evolution of the allocation coefficient between the available cumulative net energy, which was estimated from feed intake, and cumulative weight gain during the fattening period. Longitudinal energy allocation coefficients were analysed using a two-step approach to estimate both the genetic variance of the coefficients and the genetic variance in their residual variance, which will be referred to as the log-transformed squared residual (LSR). RESULTS: The LSR trait, which could be interpreted as an indicator of the response of the animal to perturbations/stress, showed a low heritability (0.05 ± 0.01), a high favourable genetic correlation with average daily growth (- 0.71 ± 0.06), and unfavourable genetic correlations with feed conversion ratio (- 0.76 ± 0.06) and residual feed intake (- 0.83 ± 0.06). Segmentation of the population in four classes using estimated breeding values for LSR showed that animals with the lowest estimated breeding values were those with the worst values for phenotypic proxies of robustness, which were assessed using records routinely collected on farm. CONCLUSIONS: Results of this study show that selection for robustness, based on estimated breeding values for environmental variance of the allocation coefficients to growth, can be considered in breeding programs for fattening pigs.

A study to investigate genetic factors associated with weight gain in people with diabetes: analysis of polymorphisms in four relevant genes.

BACKGROUND: Weight change is often seen in people with diabetes. We investigated the effects of genes associated with weight change/glucose handling/insulin-signalling. MATERIALS/METHODS: DNA from diabetes individuals and non-diabetes individuals, plus clinical data, were available from the DARE study (n = 379 individuals: T1D n = 111; T2D n = 222; controls n = 46). Weight gain was assessed by temporal change of Body Mass Index (BMI). Genotyping was performed for CAV1rs926198, LEPRrs1137101, BDNFrs6265 and FTOrs9939609. RESULTS: No differences in genotype distributions were observed for the four SNPs in all groups un-stratified by weight gain. Following stratification differences in genotype distribution were observed. For those BMI relatively stable; controls showed a difference in genotype distributions versus T1D (CAV1rs926198, LEPRrs1137101). In T2D vs controls, significant differences were observed in genotype distribution for all four genes. For BMI increase, the only difference by category was LEPRrs1137101 (bothT1D/T2D vs controls). In BMI-stable groups, CAV1rs926198, T1D individuals showed lower T allele frequency (p=0.004) vs non-diabetes and for LEPRrs1137101 a higher G allele frequency versus controls (p=0.002). For T2D, CAV1rs926198, T allele frequency was lower in T2D than controls (p=0.005). For LEPR rs1137101, the G allele frequency was higher than in controls (p=0.004). In those with BMI increase, LEPRrs1137101 T1D individuals had higher G allele frequency versus controls (p=0.002) as did T2D vs controls (p=0.03). CONCLUSION: Differences in allele frequency were seen between diabetes individuals and non-diabetes diagnosed at baseline in relation to the likelihood of BMI increase of >10%. It is established that the G allele of LEPRrs1137101 is associated with weight gain/obesity. However, this is the first report of CAV1rs926198 polymorphism being associated with weight stability/gain in diabetes.

Abdominal Obesity Genetic Variants Predict Waist Circumference Regain After Weight Loss.

Although many individuals are able to achieve weight loss, maintaining this loss over time is challenging. We aimed to study whether genetic predisposition to general or abdominal obesity predicts weight regain after weight loss. We examined the associations between genetic risk scores for higher BMI and higher waist-to-hip ratio adjusted for BMI (WHRadjBMI) with changes in weight and waist circumference up to 3 years after a 1-year weight loss program in participants (n = 822 women, n = 593 men) from the Look AHEAD (Action for Health in Diabetes) study who had lost ≥3% of their initial weight. Genetic predisposition to higher BMI or WHRadjBMI was not associated with weight regain after weight loss. However, the WHRadjBMI genetic score did predict an increase in waist circumference independent of weight change. To conclude, a genetic predisposition to higher WHRadjBMI predicts an increase in abdominal obesity after weight loss, whereas genetic predisposition to higher BMI is not predictive of weight regain. These results suggest that genetic effects on abdominal obesity may be more pronounced than those on general obesity during weight regain. ARTICLE HIGHLIGHTS: Nearly all individuals who intentionally lose weight experience weight regain. Individuals with a higher genetic risk for abdominal adiposity experience increased regain in waist circumference after weight loss. Genetic predisposition to higher BMI does not predict weight regain after weight loss.

Gestational Weight Gain Relates to DNA Methylation in Umbilical Cord, Which, In Turn, Associates with Offspring Obesity-Related Parameters.

Excessive gestational weight gain (GWG) has a negative impact on offspring's health. Epigenetic modifications mediate these associations by causing changes in gene expression. We studied the association between GWG and DNA methylation in umbilical cord tissue; and determined whether the DNA methylation and the expression of corresponding annotated genes were associated with obesity-related parameters in offspring at 6 years of age. The methylated CpG sites (CpGs) associated with GWG were identified in umbilical cord tissue by genome-wide DNA methylation (n = 24). Twelve top CpGs were validated in a wider sample by pyrosequencing (n = 87), and the expression of their 5 annotated genes (SETD8, TMEM214, SLIT3, RPTOR, and HOXC8) was assessed by RT-PCR. Pyrosequencing results validated the association of SETD8, SLIT3, and RPTOR methylation with GWG and showed that higher levels of SETD8 and RPTOR methylation and lower levels of SLIT3 methylation relate to a higher risk of obesity in the offspring. The association of SETD8 and SLIT3 gene expression with offspring outcomes paralleled the association of methylation levels in opposite directions. Epigenetic changes in the umbilical cord tissue could explain, in part, the relationship between GWG and offspring obesity risk and be early biomarkers for the prevention of overweight and obesity in childhood.

The heritability of weight gain in infancy: A population-based twin study.

BACKGROUND: Rapid weight gain during infancy is a strong predictor of childhood obesity and is affected by genetic and environmental factors. Identifying ages with low heritability will allow for targeted interventions that might be able to prevent the adverse effects of childhood obesity. OBJECTIVES: The objective of the study is to estimate the heritability of weight gain from birth to defined ages during infancy, as well as during 6-month periods from birth to 18 months of age. We address this by leveraging large-scale computerised anthropometric data from the state-run network of well-baby clinics in Israel. METHODS: We performed a population-based twin study. We extracted weight measurements recorded between birth to 24 months from well-baby clinics for 9388 twin pairs born in Israel between 2011 and 2015. The reported sexes of the twins were used as a proxy for their zygosity status. We estimated the heritability of the weight z-score change from birth to specific ages and during particular periods in infancy. To assess the validity of the results, we repeated the analysis in a sub-cohort of twin pairs with complete weight measurements. RESULTS: During the first 2 years of life, heritability was lowest for birthweight ( h 2 = 0.40 ± 0.11 ). Heritability for weight gain since birth was highest at 4 months ( h 2 = 0.87 ± 0.13 ), and then gradually decreased until age 18 months ( h 2 = 0.62 ± 0.13 ). Estimating the heritability in 6-month intervals from birth to 18 months, heritability was highest during the 6-12-month interval ( h 2 = 0.84 ± 0.14 ), and was substantially lower during the subsequent 12-18-month interval ( h 2 = 0.43 ± 0.16 ). CONCLUSIONS: Heritability of weight gain decreases substantially in the second year of life, suggesting that this period could be an appropriate time for interventions for infants who are at an increased risk of childhood obesity.

Placental epigenetic marks related to gestational weight gain reveal potential genes associated with offspring obesity parameters.

OBJECTIVE: Offspring exposed to gestational obesity have an increased risk for chronic diseases. Increasing evidence suggests that epigenetics may play a mechanistic role in metabolic programming. This study aimed to identify placental DNA methylation marks associated with gestational weight gain (GWG) and to study their association with offspring obesity parameters at school age. METHODS: A global methylation array was performed in 24 placentas from mothers with different degrees of GWG (screening sample). The methylation percentage of four cytosine-guanine (CpG) sites and the relative expression of the respective annotated genes were studied in 90 additional placentas (validation sample). Associations of these epigenetic marks with clinical parameters in the offspring at 6 years of age were examined. RESULTS: The screening analysis identified 104 CpG sites (97 genes) associated with GWG. The validation analysis of four selected CpG sites (annotating for FRAT1, SNX5, and KCNK3 genes) showed that the upregulation of SNX5 methylation, the downregulation of FRAT1 methylation, and KCNK3 underexpression associated with an adverse metabolic phenotype in children of women with increased GWG. CONCLUSIONS: These results suggest that placental regulation of FRAT1, SNX5, and KCNK3 relates to obesity parameters in offspring exposed to excessive GWG and thereby could condition the risk for future metabolic disorders.

Associations of height, body mass index, and weight gain with breast cancer risk in carriers of a pathogenic variant in BRCA1 or BRCA2: the BRCA1 and BRCA2 Cohort Consortium.

INTRODUCTION: Height, body mass index (BMI), and weight gain are associated with breast cancer risk in the general population. It is unclear whether these associations also exist for carriers of pathogenic variants in the BRCA1 or BRCA2 genes. PATIENTS AND METHODS: An international pooled cohort of 8091 BRCA1/2 variant carriers was used for retrospective and prospective analyses separately for premenopausal and postmenopausal women. Cox regression was used to estimate breast cancer risk associations with height, BMI, and weight change. RESULTS: In the retrospective analysis, taller height was associated with risk of premenopausal breast cancer for BRCA2 variant carriers (HR 1.20 per 10 cm increase, 95% CI 1.04-1.38). Higher young-adult BMI was associated with lower premenopausal breast cancer risk for both BRCA1 (HR 0.75 per 5 kg/m2, 95% CI 0.66-0.84) and BRCA2 (HR 0.76, 95% CI 0.65-0.89) variant carriers in the retrospective analysis, with consistent, though not statistically significant, findings from the prospective analysis. In the prospective analysis, higher BMI and adult weight gain were associated with higher postmenopausal breast cancer risk for BRCA1 carriers (HR 1.20 per 5 kg/m2, 95% CI 1.02-1.42; and HR 1.10 per 5 kg weight gain, 95% CI 1.01-1.19, respectively). CONCLUSION: Anthropometric measures are associated with breast cancer risk for BRCA1 and BRCA2 variant carriers, with relative risk estimates that are generally consistent with those for women from the general population.

Genetic evaluation of growth rate and efficiency-related traits in Dorper × local crossbred sheep population.

The present study was carried out to estimate genetic and phenotypic parameters for growth rate and efficiency-related traits in Dorper crossbred sheep population. Data on body weight collected from 2012 to 2021 at Debre Birhan Agricultural Research Center, Amhara Regional State, Ethiopia, were used to estimate phenotypic and genetic parameters for daily gain from birth to weaning (DG0-3), daily gain from weaning to 6 months (DG3-6), and daily gain from 6 months to yearling (DG6-12) and corresponding Kleiber ratios (KR0-3, KR3-6, KR6-12), efficiency of growth (GE0-3, GE3-6, GE6-12), and relative growth rate (RG0-3, RG3-6, RG6-12). Genetic parameters were estimated by restricted maximum likelihood (REML) procedure fitting six different univariate animal models and the most appropriate model for each trait was determined by log-likelihood ratio test. Multivariate analysis was carried out to estimate correlations between traits. Year and season of birth had a significant effect (p<0.001) in all studied traits. Direct heritability estimates for DG0-3, DG3-6, DG6-12, KR0-3, KR3-6, KR6-12, GE0-3, GE3-6, GE6-12, GR0-3, GR3-6, and GR6-12 were 0.45±0.15, 0.04±0.06, 0.15±0.11, 0.30±0.08, 0.13±0.11, 0.14±0.12, 0.34±0.15, 0.39±0.17, 0.31±0.14, 0.25±0.08, 0.23±0.13, and 0.23±0.13 respectively. Genetic correlation estimates between DG3-6 and other traits were positive and high in magnitude to their respective growth phase (0.95, 0.86, and 0.91 for KR3-6, GE3-6, and GR3-6 respectively). As the Dorper crossbred sheep are reaches market weight at about 6 months of age, focusing on improving traits measured during weaning to 6 months of age is more feasible. Selection based on DG3-6 is recommended to improve efficiency-related traits.

Identification of four novel loci associated with psychotropic drug-induced weight gain in a Swiss psychiatric longitudinal study: A GWAS analysis.

Patients suffering from mental disorders are at high risk of developing cardiovascular diseases, leading to a reduction in life expectancy. Genetic variants can display greater influence on cardiometabolic features in psychiatric cohorts compared to the general population. The difference is possibly due to an intricate interaction between the mental disorder or the medications used to treat it and metabolic regulations. Previous genome wide association studies (GWAS) on antipsychotic-induced weight gain included a low number of participants and/or were restricted to patients taking one specific antipsychotic. We conducted a GWAS of the evolution of body mass index (BMI) during early (i.e., ≤ 6) months of treatment with psychotropic medications inducing metabolic disturbances (i.e., antipsychotics, mood stabilizers and some antidepressants) in 1135 patients from the PsyMetab cohort. Six highly correlated BMI phenotypes (i.e., BMI change and BMI slope after distinct durations of psychotropic treatment) were considered in the analyses. Our results showed that four novel loci were associated with altered BMI upon treatment at genome-wide significance (p < 5 × 10-8): rs7736552 (near MAN2A1), rs11074029 (in SLCO3A1), rs117496040 (near DEFB1) and rs7647863 (in IQSEC1). Associations between the four loci and alternative BMI-change phenotypes showed consistent effects. Replication analyses in 1622 UK Biobank participants under psychotropic treatment showed a consistent association between rs7736552 and BMI slope (p = 0.017). These findings provide new insights into metabolic side effects induced by psychotropic drugs and underline the need for future studies to replicate these associations in larger cohorts.

Genetic parameters for mouth size and their influence on growth traits in pasture-raised Nelore cattle.

Evaluating traits that allow breeders to increase production efficiency in beef production systems is important. The mouth size (MS) score is a trait easily measured and implemented by breeders. Bite size is related to MS in beef cattle and is a determinant of daily feed intake of pasture-raised animals, influencing their growth. The aim of this study was to estimate genetic parameters for MS, weaning weight (WW) and postweaning weight gain (PWG) of Nelore cattle and to evaluate the influence of the interaction between MS and WW on PWG. Phenotypic records of 134,282 Nelore animals born between 1995 and 2019 were used. Variance components were estimated using multitrait animal model with the Bayesian method. The model included the contemporary group as fixed effect, age at measurement of the trait as linear covariate, and direct additive genetic and residual effects as random effects. For WW, random maternal and maternal permanent environmental effects were added to the model. A Bayesian approach was used to analyze the interaction between WW clusters and MS. The heritability estimates were 0.24, 0.15, and 0.23 for MS, WW, and PWG, respectively. The genetic correlation between variables studied ranged from 0.24 to 0.46. The results suggest that animals with a larger mouth tend to have greater PWG, demonstrating the positive influence of MS score on the postweaning performance of cattle. The direct heritability estimates confirm the possibility of selecting animals for the traits studied.

Evaluating traits that allow breeders to increase production efficiency in beef production systems is important. The mouth size (MS) score is a trait easily measured and implemented by breeders. Our results showed that MS in Nelore cattle is a heritable trait, and it is favorably associated with growth traits, indicating that animals with larger mouth are heavier at weaning and gain more weight after weaning on pasture. MS score should be further explored to evaluate its complexity and inclusion in breeding programs incorporating data collected from cattle raised under pasture conditions.

Estimates of genetic parameters and genetic trend for growth traits and Kleiber ratio of Holstein-Friesian calves.

Growth traits of calves, which are quantitative characteristics determining cattle business profitability, vary according to genetic and environmental factors. In other words, growth traits depend on the genetics of the individual and vary with farm management. The aim of this study was to investigate the effective environmental factors, genetic parameters, and genetic trends for some growth traits and the Kleiber ratio (KR) in Holstein-Friesian calves. For this purpose, the records of 724 calves, progeny of 566 dams and 29 sires, reared between 2017 and 2019 on a private dairy farm in Türkiye, were used. MTDFREML software was utilized to estimate genetic parameters and genetic trends of growth traits and KR. In this study, regarding weight, the mean of birth weight (BW), 60-day weight (W60), and 90-day weight (W90) were 39.76 ± 6.15 kg, 69.23 ± 10.93 kg, and 95.76 ± 16.48 kg, respectively. Concerning weight gain, 1-60 daily weight gain (DWG1-60), 60-90 daily weight gain (DWG60-90), and 1-90 daily weight gain (DWG1-90) were 0.49 ± 0.16 kg, 0.91 ± 0.34 kg, and 0.63 ± 0.17 kg, respectively. With respect to KR, 1-60 daily KR (KR1-60), 60-90 daily KR (KR60-90), and 1-90 daily KR (KR1-90) were 2.03 ± 0.48, 2.93 ± 0.89, and 2.02 ± 0.34, respectively. As a result of the GLM analysis, only the effect of the birth season on all traits was significant (p < 0.05 or p < 0.01). In addition, it was detected that sex had a significant effect on BW and W60 (p < 0.05 or p < 0.01). For all traits, only the effect of parity on KR1-60 was not significant. In REML analysis, direct heritability differed between 0.26 ± 0.16 and 0.81 ± 0.27 obtained at DWG1-90 and DWG1-60, respectively. Also, the highest repeatability (0.100) was obtained in DWG1-60. It was detected that mass selection could be used in all traits for breeding program. In BLUP analysis, the current population had an increasing trend for BW and W90 and a decreasing trend for W60. However, there was no significant change in other weight gain traits and KR over the years. Calves with high breeding values for BW, W60, W90, DWG1-60, DWG60-90, and DWG1-90 should be chosen for selection programs. But for KR1-60, KR60-90, and KR1-90, calves with low breeding values should be selected for efficiency. Also, KR evaluated would contribute to the literature and other research should be studied regarding KR.