RESUMEN
Methyltransferase-like 23 (METTL23) is a kind of RNA methyltransferase that catalyzes the methylation transfer to the N6-adenosine of RNA, serving as one of the key mediators in this process. However, the METTL23 gene has been poorly researched in pigs. In this study, we investigated the genetic effects of METTL23 single-nucleotide polymorphism(SNPs) on reproductive traits in Kele pigs. The DNA was extracted from 228 healthy multiparous Kele sows, and Sanger sequencing revealed three SNPs, g.4804958 G > T (intron 2), g.4805082 C > T (exon 2), and g.4806821 A > G (exon 3). The polymorphism information content (PIC) for each SNP was 0.264, 0.25, and 0.354, indicating moderate polymorphism (0.25 < PIC < 0.5) and providing genetic information. Linkage disequilibrium analysis showed no strong linkage disequilibrium between the three SNPs. The association analysis revealed that in the SNP g.4804958 G > T individuals with the GG genotype had a significantly higher number of piglets born alive, litter birth weight, number of weaned piglets, and weaning litter weight compared to those with the TT genotype (p < 0.05). Individuals with the GG genotype in the SNP g.4806821 A > G group had significantly higher litter birth weight and average birth weight than those with the AA genotype (p < 0.05). The H4H4 diplotype showed significant effects on the number of piglets born alive, litter birth weight, number of weaned piglets, weaning litter weight, and weaning weight (p < 0.05). Together, the METTL23 gene could be used as a candidate gene for the selection of reproductive traits in Kele pigs.
Asunto(s)
Metiltransferasas , Polimorfismo de Nucleótido Simple , Reproducción , Animales , Metiltransferasas/genética , Porcinos/genética , Reproducción/genética , Femenino , Desequilibrio de Ligamiento , Tamaño de la Camada/genética , Genotipo , Peso al Nacer/genética , Estudios de Asociación GenéticaRESUMEN
Objectives: Maternal stress has long been associated with lower birthweight, which is associated with adverse health outcomes including many adult diseases. The underlying mechanisms remain elusive although changes in gene expression may play a role. Studies are only beginning to test how maternal stress impacts gene expression as reflected in the transcriptome. Materials and Methods: In a cohort of mothers and newborns in the eastern Democratic Republic of Congo (n=93), we studied the effects of four maternal stress measures (chronic stress, war trauma, sexual trauma, and general trauma) on the transcriptomes of maternal venous blood, newborn venous blood, and placental tissues, and on newborn birthweight. Maternal stress was investigated as independent measures, principal components, and clusters identified through machine learning. The transcriptome was assayed using the ClariomD chip. Multiple regression models were used to test for associations between maternal stress measures, the transcriptome, and newborn birthweight. Results: None of the maternal stress measures showed an association with expression of individual genes. In contrast, when testing global gene expression, war trauma was significantly associated with the placental transcriptome. War trauma was also significantly associated with birthweight in multiple models. Mediation analysis indicated that ~14% of the effect of war trauma on birthweight was mediated by a placental gene expression component. Discussion: Our results suggest that gene expression in the placenta, which represents the interface between mother and developing fetus, may partially mediate the negative impact of maternal stress on newborn birthweight.
Asunto(s)
Peso al Nacer , Humanos , República Democrática del Congo/epidemiología , Femenino , Recién Nacido , Peso al Nacer/genética , Embarazo , Adulto , Estrés Psicológico/genética , Placenta/metabolismo , Transcriptoma , Adulto Joven , Expresión GénicaRESUMEN
BACKGROUND: Observational studies have shown that childhood obesity is associated with adult bone health but yield inconsistent results. We aimed to explore the potential causal association between body shape and skeletal development. METHODS: We used two-sample Mendelian randomization (MR) to estimate causal relationships between body shape from birth to adulthood and skeletal phenotypes, with exposures including placental weight, birth weight, childhood obesity, BMI, lean mass, fat mass, waist circumference, and hip circumference. Independent genetic instruments associated with the exposures at the genome-wide significance level (P < 5 × 10-8) were selected from corresponding large-scale genome-wide association studies. The inverse-variance weighted analysis was chosen as the primary method, and complementary MR analyses included the weighted median, MR-Egger, weighted mode, and simple mode. RESULTS: The MR analysis shows strong evidence that childhood (ß = -1.29 × 10-3, P = 8.61 × 10-5) and adulthood BMI (ß = -1.28 × 10-3, P = 1.45 × 10-10) were associated with humerus length. Tibiofemoral angle was negatively associated with childhood BMI (ß = -3.60 × 10-1, P = 3.00 × 10-5) and adolescent BMI (ß = -3.62 × 10-1, P = 2.68 × 10-3). In addition, genetically predicted levels of appendicular lean mass (ß = 1.16 × 10-3, P = 1.49 × 10-13), whole body fat mass (ß = 1.66 × 10-3, P = 1.35 × 10-9), waist circumference (ß = 1.72 × 10-3, P = 6.93 × 10-8) and hip circumference (ß =1.28 × 10-3, P = 4.34 × 10-6) were all associated with tibia length. However, we found no causal association between placental weight, birth weight and bone length/width. CONCLUSIONS: This large-scale MR analysis explores changes in growth patterns in the length/width of major bone sites, highlighting the important role of childhood body shape in bone development and providing insights into factors that may drive bone maturation.
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Desarrollo Óseo , Análisis de la Aleatorización Mendeliana , Humanos , Adulto , Desarrollo Óseo/genética , Estudio de Asociación del Genoma Completo , Tamaño Corporal/genética , Femenino , Niño , Índice de Masa Corporal , Adolescente , Masculino , Peso al Nacer/genética , Recién NacidoRESUMEN
BACKGROUND: Maternal genetic risk of type 2 diabetes (T2D) has been associated with fetal growth, but the influence of genetic ancestry is not yet fully understood. We aimed to investigate the influence of genetic distance (GD) and genetic ancestry proportion (GAP) on the association of maternal genetic risk score of T2D (GRST2D) with fetal weight and birthweight. METHODS: Multi-ancestral pregnant women (n = 1,837) from the NICHD Fetal Growth Studies - Singletons cohort were included in the current analyses. Fetal weight (in grams, g) was estimated from ultrasound measurements of fetal biometry, and birthweight (g) was measured at delivery. GRST2D was calculated using T2D-associated variants identified in the latest trans-ancestral genome-wide association study and was categorized into quartiles. GD and GAP were estimated using genotype data of four reference populations. GD was categorized into closest, middle, and farthest tertiles, and GAP was categorized as highest, medium, and lowest. Linear regression analyses were performed to test the association of GRST2D with fetal weight and birthweight, adjusted for covariates, in each GD and GAP category. RESULTS: Among women with the closest GD from African and Amerindigenous ancestries, the fourth and third GRST2D quartile was significantly associated with 5.18 to 7.48 g (weeks 17-20) and 6.83 to 25.44 g (weeks 19-27) larger fetal weight compared to the first quartile, respectively. Among women with middle GD from European ancestry, the fourth GRST2D quartile was significantly associated with 5.73 to 21.21 g (weeks 18-26) larger fetal weight. Furthermore, among women with middle GD from European and African ancestries, the fourth and second GRST2D quartiles were significantly associated with 117.04 g (95% CI = 23.88-210.20, p = 0.014) and 95.05 g (95% CI = 4.73-185.36, p = 0.039) larger birthweight compared to the first quartile, respectively. The absence of significant association among women with the closest GD from East Asian ancestry was complemented by a positive significant association among women with the highest East Asian GAP. CONCLUSIONS: The association between maternal GRST2D and fetal growth began in early-second trimester and was influenced by GD and GAP. The results suggest the use of genetic GD and GAP could improve the generalizability of GRS.
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Peso al Nacer , Diabetes Mellitus Tipo 2 , Desarrollo Fetal , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Femenino , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/epidemiología , Embarazo , Desarrollo Fetal/genética , Peso al Nacer/genética , Adulto , Peso Fetal/genética , Factores de Riesgo , Polimorfismo de Nucleótido Simple/genética , Puntuación de Riesgo GenéticoRESUMEN
Tibetan sheep are vital to the ecosystem and livelihood of the Tibetan Plateau; however, traditional breeding methods limit their production and growth. Modern molecular breeding techniques are required to improve these traits. This study identified a single nucleotide polymorphism (SNP) in myostatin (MSTN) and Callipyge in Tibetan sheep. The findings indicated notable associations between MSTN genotypes and growth traits including birth weight (BW), body length (BL), chest width (ChW), and chest circumference (ChC), as well as a particularly strong association with cannon circumference (CaC) at 2 months of age. Conversely, Callipyge polymorphisms did not have a significant impact on Tibetan sheep. Moreover, the analyses revealed a significant association between sex and BW or hip width (HW) at 2 months of age and ChW, ChC, and CaC at 4 months of age. Furthermore, the study's results suggested that the genotype of MSTN as a GA was associated with a notable sex effect on BW, while the genotype of Callipyge (CC) showed a significant impact of sex on CaC at 2 months of age. These results indicated that the SNP of MSTN could potentially serve as a molecular marker for early growth traits in Tibetan sheep.
Asunto(s)
Miostatina , Polimorfismo de Nucleótido Simple , Animales , Miostatina/genética , Ovinos/genética , Ovinos/crecimiento & desarrollo , Femenino , Masculino , Tibet , Genotipo , Fenotipo , Peso al Nacer/genética , CruzamientoRESUMEN
BACKGROUND: Observational studies have revealed associations between birth weight, childhood obesity, age at menarche, and ovarian dysfunction. However, these studies are susceptible to unavoidable confounding factors, leading to ongoing debates regarding their conclusions and making causal relationships challenging to infer. In light of these challenges, Mendelian randomization was employed in this study to investigate the causal relationships between birth weight, childhood obesity, age at menarche, and ovarian dysfunction. METHODS: This study employed a two-sample Mendelian randomization approach using genetic variation as instrumental variables to investigate causal relationships. Genetic variation data were sourced from summary data of genome-wide association studies in European populations. Instrumental variables were selected based on the principles of Mendel's three assumptions. The study utilized the inverse variance weighted method to assess the relationships between birth weight, childhood obesity, age at menarche, and ovarian dysfunction. Supplementary analyses were conducted using MR-Egger regression, the weighted median method, and the weighted median mode to complement the IVW results. Furthermore, the study conducted heterogeneity, horizontal pleiotropy, and sensitivity analyses to evaluate the robustness of the results. RESULTS: Based on the inverse variance weighted method, it was found that there exists a causal relationship between childhood obesity (OR = 1.378, 95% CI: 1.113â¼1.705, p = 0.003), age at menarche (OR = 0.639, 95% CI: 0.468â¼0.871, p = 0.005), and ovarian dysfunction, while no causal relationship was observed between birth weight and ovarian dysfunction. Heterogeneity tests, multiplicity tests, and leave-one-out sensitivity analyses did not detect any heterogeneity or multiplicity effects in the estimated impact of these three exposure factors on the risk of ovarian dysfunction. CONCLUSIONS: This study represents the first evidence suggesting a potential causal relationship between childhood obesity, age at menarche, and ovarian dysfunction. Childhood obesity was found to increase the risk of ovarian dysfunction, while a later age at menarche was associated with a reduced risk of ovarian dysfunction.
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Peso al Nacer , Menarquia , Análisis de la Aleatorización Mendeliana , Obesidad Infantil , Humanos , Menarquia/genética , Femenino , Obesidad Infantil/genética , Obesidad Infantil/epidemiología , Peso al Nacer/genética , Niño , Estudio de Asociación del Genoma Completo , Factores de Riesgo , Adolescente , Factores de EdadRESUMEN
Birth weight is a complex multifactorial trait relevant to health states and disease risks in later life. The placenta is essential for proper fetal growth and facilitates gas, nutrient, and waste exchange between the mother and developing fetus. How changes in placental DNA methylation affect fetal birth weight remains to be fully elucidated. In this study, we used whole-genome bisulfite sequencing and RNA sequencing to reveal a global map of DNA methylation and gene expression changes between the placentas of highest birth weight and lowest birth weight piglets in the same litters. The transcriptome analysis identified 1682 differential expressed genes and revealed key transcriptional properties in distinct placentas. We also identified key transcription factors that may drive the differences in DNA methylome patterns between placentas. The decrease in DNA methylation level in the promoter was associated with the transcriptional activation of genes associated with angiogenesis, extracellular matrix remodeling, and transmembrane transport. Our results revealed the regulatory role of DNA methylation in gene transcription activity leading to the differences in placental morphological structures and birth weights of piglets. These results could provide novel clues to clarify the underlying regulatory mechanisms of placental development and fetal growth.
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Peso al Nacer , Metilación de ADN , Placenta , Animales , Femenino , Embarazo , Placenta/metabolismo , Peso al Nacer/genética , Porcinos , Perfilación de la Expresión Génica , Desarrollo Fetal/genética , Regulación del Desarrollo de la Expresión Génica , TranscriptomaRESUMEN
Inbreeding depression, the loss of offspring fitness due to consanguineous mating, is generally detrimental for individual performance and population viability. We investigated inbreeding effects in a declining population of Antarctic fur seals (Arctocephalus gazella) at Bird Island, South Georgia. Here, localised warming has reduced the availability of the seal's staple diet, Antarctic krill, leading to a temporal increase in the strength of selection against inbred offspring, which are increasingly failing to recruit into the adult breeding population. However, it remains unclear whether selection operates before or after nutritional independence at weaning. We therefore used microsatellite data from 885 pups and their mothers, and SNP array data from 98 mother-offspring pairs, to quantify the effects of individual and maternal inbreeding on three important neonatal fitness traits: birth mass, survival and growth. We did not find any clear or consistent effects of offspring or maternal inbreeding on any of these traits. This suggests that selection filters inbred individuals out of the population as juveniles during the time window between weaning and recruitment. Our study brings into focus a poorly understood life-history stage and emphasises the importance of understanding the ecology and threats facing juvenile pinnipeds.
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Lobos Marinos , Depresión Endogámica , Animales , Lobos Marinos/fisiología , Lobos Marinos/genética , Regiones Antárticas , Femenino , Masculino , Endogamia , Repeticiones de Microsatélite , Polimorfismo de Nucleótido Simple , Peso al Nacer/genéticaRESUMEN
It is possible to identify sub-populations of sows in every pig herd that consistently give birth to low birth weight (BW) piglets, irrespective of the litter size. A previous study from our group demonstrated that placental development is a main factor affecting the litter birth weight phenotype (LBWP) in sows, thereby impacting the BW of entire litters, but the biological and molecular pathways behind this phenomenon are largely unknown. The aim of this study was to investigate the differential gene expression in placental tissues at day 30 of gestation between low LBWP (LLBWP) vs. high LBWP (HLBWP) sows from a purebred Large White maternal line. Using mRNA sequencing, we found 45 differentially expressed genes (DEGs) in placental tissues of LLBWP and HLBWP sows. Furthermore, (GO) enrichment of upregulated DEGs predicted that there were two biological processes significantly related to cornification and regulation of cell population proliferation. To better understand the molecular interaction between cell proliferation and cornification, we conducted transcriptional factor binding site (TFBS) prediction analysis. The results indicated that a highly significant TFBS was located at the 5' upstream of all four upregulated genes (CDSN, DSG3, KLK14, KRT17), recognized by transcription factors EGR4 and FOSL1. Our findings provide novel insight into how transcriptional regulation of two different biological processes interact in placental tissues of LLBWP sows.
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Peso al Nacer , Placenta , Animales , Femenino , Embarazo , Placenta/metabolismo , Porcinos/genética , Peso al Nacer/genética , Transcriptoma , Tamaño de la Camada/genética , Fenotipo , Perfilación de la Expresión Génica/métodosRESUMEN
Body weight is an important economic trait for sheep meat production, and its genetic improvement is considered one of the main goals in the sheep breeding program. Identifying genomic regions that are associated with growth-related traits accelerates the process of animal breeding through marker-assisted selection, which leads to increased response to selection. In this study, we conducted a weighted single-step genome-wide association study (WssGWAS) to identify potential candidate genes for direct and maternal genetic effects associated with birth weight (BW) and weaning weight (WW) in Baluchi sheep. The data used in this research included 13,408 birth and 13,170 weaning records collected at Abbas-Abad Baluchi Sheep Breeding Station, Mashhad-Iran. Genotypic data of 94 lambs genotyped by Illumina 50K SNP BeadChip for 54,241 markers were used. The proportion of variance explained by genomic windows was calculated by summing the variance of SNPs within 1 megabase (Mb). The top 10 window genomic regions explaining the highest percentages of additive and maternal genetic variances were selected as candidate window genomic regions associated with body weights. Our findings showed that for BW, the top-ranked genomic regions (1 Mb windows) explained 4.30 and 4.92% of the direct additive and maternal genetic variances, respectively. The direct additive genetic variance explained by the genomic window regions varied from 0.31 on chromosome 1 to 0.59 on chromosome 8. The highest (0.84%) and lowest (0.32%) maternal genetic variances were explained by genomic windows on chromosome 10 and 17, respectively. For WW, the top 10 genomic regions explained 6.38 and 5.76% of the direct additive and maternal genetic variances, respectively. The highest and lowest contribution of direct additive genetic variances were 1.37% and 0.42%, respectively, both explained by genomic regions on chromosome 2. For maternal effects on WW, the highest (1.38%) and lowest (0.41%) genetic variances were explained by genomic windows on chromosome 2. Further investigation of these regions identified several possible candidate genes associated with body weight. Gene ontology analysis using the DAVID database identified several functional terms, such as translation repressor activity, nucleic acid binding, dehydroascorbic acid transporter activity, growth factor activity and SH2 domain binding.
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Peso al Nacer , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Destete , Animales , Femenino , Ovinos/genética , Peso al Nacer/genética , Sitios de Carácter Cuantitativo , Peso Corporal/genética , Herencia Materna , Cruzamiento , Genotipo , Masculino , FenotipoRESUMEN
Background: The association between birth weight and childhood body mass index (BMI) and frailty has been extensively studied, but it is currently unclear whether this relationship is causal. Methods: We utilized a two-sample Mendelian randomization (MR) methodology to investigate the causal effects of birth weight and childhood BMI on the risk of frailty. Instrumental variables (p < 5E-08) strongly associated with own birth weight (N = 298,142 infants), offspring birth weight (N = 210,267 mothers), and childhood BMI (N = 39,620) were identified from large-scale genomic data from genome-wide association studies (GWAS). The frailty status was assessed using the frailty index, which was derived from comprehensive geriatric assessments of older adults within the UK Biobank and the TwinGene database (N = 175,226). Results: Genetically predicted one standard deviation (SD) increase in own birth weight, but not offspring birth weight (maternal-specific), was linked to a decreased frailty index (ß per SD increase = -0.068, 95%CI = -0.106 to -0.030, p = 3.92E-04). Conversely, genetically predicted one SD increase in childhood BMI was associated with an elevated frailty index (ß per SD increase = 0.080, 95%CI = 0.046 to 0.114, p = 3.43E-06) with good statistical power (99.8%). The findings remained consistent across sensitivity analyses and showed no horizontal pleiotropy (p > 0.05). Conclusion: This MR study provides evidence supporting a causal relationship between lower birth weight, higher childhood BMI, and an increased risk of frailty.
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Peso al Nacer , Índice de Masa Corporal , Fragilidad , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Humanos , Peso al Nacer/genética , Fragilidad/genética , Femenino , Masculino , Anciano , Factores de Riesgo , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: The aim of this study was to investigate the methylenetetrahydrofolate reductase (MTHFR) 677 C > T gene polymorphism in term infants born small (SGA), appropriate (AGA), and large for gestational age (LGA). METHODS: The study comprised 165 newborns with SGA, LGA and AGA. Genomic DNA was isolated from the peripheral blood. Samples were genotyped for MTHFR 677 C > T gene polymorphisms using PCR-RFLP. RESULTS: There was a statistically significant difference between the genotype and their allelic distribution of AGA, SGA, and LGA. The newborns carrying the TT genotype had higher birth weight than those carrying the CC and CT genotypes. The frequency of MTHFR 677 TT genotype and T allele was significantly higher and was found to be linked with a higher risk in LGA than in the AGA group. CONCLUSIONS: The MTHFR 677 C > T gene polymorphism can be used as a genetic marker in Turkish LGA newborns, but not in SGA.
Asunto(s)
Peso al Nacer , Recién Nacido Pequeño para la Edad Gestacional , Metilenotetrahidrofolato Reductasa (NADPH2) , Polimorfismo de Nucleótido Simple , Humanos , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Recién Nacido , Femenino , Masculino , Peso al Nacer/genética , Genotipo , Edad Gestacional , Frecuencia de los Genes , TurquíaRESUMEN
BACKGROUND: Recursive models are a category of structural equation models that propose a causal relationship between traits. These models are more parameterized than multiple trait models, and they require imposing restrictions on the parameter space to ensure statistical identification. Nevertheless, in certain situations, the likelihood of recursive models and multiple trait models are equivalent. Consequently, the estimates of variance components derived from the multiple trait mixed model can be converted into estimates under several recursive models through LDL' or block-LDL' transformations. RESULTS: The procedure was employed on a dataset comprising five traits (birth weight-BW, weight at 90 days-W90, weight at 210 days-W210, cold carcass weight-CCW and conformation-CON) from the Pirenaica beef cattle breed. These phenotypic records were unequally distributed among 149,029 individuals and had a high percentage of missing data. The pedigree used consisted of 343,753 individuals. A Bayesian approach involving a multiple-trait mixed model was applied using a Gibbs sampler. The variance components obtained at each iteration of the Gibbs sampler were subsequently used to estimate the variance components within three distinct recursive models. CONCLUSIONS: The LDL' or block-LDL' transformations applied to the variance component estimates achieved from a multiple trait mixed model enabled inference across multiple sets of recursive models, with the sole prerequisite of being likelihood equivalent. Furthermore, the aforementioned transformations simplify the handling of missing data when conducting inference within the realm of recursive models.
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Modelos Genéticos , Animales , Bovinos/genética , Teorema de Bayes , Fenotipo , Cruzamiento/métodos , Cruzamiento/normas , Peso al Nacer/genética , Linaje , Carácter Cuantitativo HeredableRESUMEN
Inner Mongolia cashmere goat is an excellent livestock breed formed through long-term natural selection and artificial breeding, and is currently a world-class dual-purpose breed producing cashmere and meat. Multi trait animal model is considered to significantly improve the accuracy of genetic evaluation in livestock and poultry, enabling indirect selection between traits. In this study, the pedigree, genotype, environment, and phenotypic records of early growth traits of Inner Mongolia cashmere goats were used to build multi trait animal model., Then three methods including ABLUP, GBLUP, and ssGBLUP wereused to estimate the genetic parameters and genomic breeding values of early growth traits (birth weight, weaning weight, average daily weight gain before weaning, and yearling weight). The accuracy and reliability of genomic estimated breeding value are further evaluated using the five fold cross validation method. The results showed that the heritability of birth weight estimated by three methods was 0.13-0.15, the heritability of weaning weight was 0.13-0.20, heritability of daily weight gain before weaning was 0.11-0.14, and the heritability of yearling weight was 0.09-0.14, all of which belonged to moderate to low heritability. There is a strong positive genetic correlation between weaning weight and daily weight gain before weaning, daily weight gain before weaning and yearling weight, with correlation coefficients of 0.77-0.79 and 0.56-0.67, respectively. The same pattern was found in phenotype correlation among traits. The accuracy of the estimated breeding values by ABLUP, GBLUP, and ssGBLUP methods for birth weight is 0.5047, 0.6694, and 0.7156, respectively; the weaning weight is 0.6207, 0.6456, and 0.7254, respectively; the daily weight gain before weaning was 0.6110, 0.6855, and 0.7357 respectively; and the yearling weight was 0.6209, 0.7155, and 0.7756, respectively. In summary, the early growth traits of Inner Mongolia cashmere goats belong to moderate to low heritability, and the speed of genetic improvement is relatively slow. The genetic improvement of other growth traits can be achieved through the selection of weaning weight. The ssGBLUP method has the highest accuracy and reliability in estimating genomic breeding value of early growth traits in Inner Mongolia cashmere goats, and is significantly higher than that from ABLUP method, indicating that it is the best method for genomic breeding of early growth weight in Inner Mongolia cashmere goats.
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Cruzamiento , Cabras , Animales , Cabras/genética , Cabras/crecimiento & desarrollo , Fenotipo , Genómica/métodos , Femenino , Masculino , Peso al Nacer/genética , Modelos GenéticosRESUMEN
The Y chromosome is classified into haplogroups (A-T) based on a combination of several DNA polymorphisms. Japanese men are mainly classified into haplogroups C, D, and O, which have been further subdivided. The distribution of Y-chromosome haplogroups varies by ethnicity. The phylogenetic age, origin, and migration also differ. I hypothesized that Y chromosome haplogroups may be associated with height and/or weight at birth. An association analysis of height and weight at birth with Y chromosome haplogroups was performed in 288 Japanese men. Men belonging to haplogroup O1b2 were significantly associated with short stature at birth (beta = ï¼1.88, standard error (SE) = 0.55, P = 0.00076), and those belonging to D1a2a-12f2b were significantly associated with increased birth weight (beta = 174, SE = 64, P = 0.0069). Y chromosome haplogroups are associated with physical birth characteristics in modern Japanese men. J. Med. Invest. 71 : 129-133, February, 2024.
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Peso al Nacer , Cromosomas Humanos Y , Haplotipos , Adulto , Humanos , Masculino , Peso al Nacer/genética , Estatura/genética , Cromosomas Humanos Y/genética , Pueblos del Este de Asia/genética , JapónRESUMEN
BACKGROUND: The causal relationship between maternal smoking in pregnancy and reduced offspring birth weight is well established and is likely due to impaired placental function. However, observational studies have given conflicting results on the association between smoking and placental weight. We aimed to estimate the causal effect of newly pregnant mothers quitting smoking on their placental weight at the time of delivery. METHODS: We used one-sample Mendelian randomization, drawing data from the Avon Longitudinal Study of Parents and Children (ALSPAC) (N = 690 to 804) and the Norwegian Mother, Father and Child Cohort Study (MoBa) (N = 4267 to 4606). The sample size depends on the smoking definition used for different analyses. The analysis was performed in pre-pregnancy smokers only, due to the specific role of the single-nucleotide polymorphism (SNP) rs1051730 (CHRNA5 - CHRNA3 - CHRNB4) in affecting smoking cessation but not initiation. RESULTS: Fixed effect meta-analysis showed a 182 g [95%CI: 29,335] higher placental weight for pre-pregnancy smoking mothers who continued smoking at the beginning of pregnancy, compared with those who stopped smoking. Using the number of cigarettes smoked per day in the first trimester as the exposure, the causal effect on placental weight was 11 g [95%CI: 1,21] per cigarette per day. Similarly, smoking at the end of pregnancy was causally associated with higher placental weight. Using the residuals of birth weight regressed on placental weight as the outcome, we showed evidence of lower offspring birth weight relative to the placental weight, both for continuing smoking at the start of pregnancy as well as continuing smoking throughout pregnancy (change in z-score birth weight adjusted for z-score placental weight: -0.8 [95%CI: -1.6,-0.1]). CONCLUSION: Our results suggest that continued smoking during pregnancy causes higher placental weights.
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Análisis de la Aleatorización Mendeliana , Placenta , Femenino , Humanos , Embarazo , Peso al Nacer/genética , Estudios de Cohortes , Estudios Longitudinales , Fumar/efectos adversosRESUMEN
BACKGROUND: Observational studies have suggested an association between birth weight and type 2 diabetes mellitus, but the causality between them has not been established. We aimed to obtain the causal relationship between birth weight with T2DM and quantify the mediating effects of potential modifiable risk factors. METHODS: Two-step, two-sample Mendelian randomization (MR) techniques were applied using SNPs as genetic instruments for exposure and mediators. Summary data from genome-wide association studies (GWAS) for birth weight, T2DM, and a series of fatty acids traits and their ratios were leveraged. The inverse variance weighted (IVW) method was the main analysis approach. In addition, the heterogeneity test, horizontal pleiotropy test, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test, and leave-one-out analysis were carried out to assess the robustness. RESULTS: The IVW method showed that lower birth weight raised the risk of T2DM (ß: -1.113, 95% CI: -1.573 â¼ -0.652). Two-step MR identified 4 of 17 candidate mediators partially mediating the effect of lower birth weight on T2DM, including ratio of polyunsaturated fatty acids to monounsaturated fatty acids (proportion mediated: 7.9%), ratio of polyunsaturated fatty acids to total fatty acids (7.2%), ratio of omega-6 fatty acids to total fatty acids (8.1%) and ratio of linoleic acid to total fatty acids ratio (6.0%). CONCLUSIONS: Our findings supported a potentially causal effect of birth weight against T2DM with considerable mediation by modifiable risk factors. Interventions that target these factors have the potential to reduce the burden of T2DM attributable to low birth weight.
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Diabetes Mellitus Tipo 2 , Ácidos Grasos , Humanos , Diabetes Mellitus Tipo 2/genética , Peso al Nacer/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Ácidos Grasos MonoinsaturadosRESUMEN
OBJECTIVES: This study aims to comprehensively investigate the potential genetic link between periodontitis and adverse pregnancy outcomes using a two-sample Mendelian Randomization approach. MATERIALS AND METHODS: We employed robust genetic instruments for chronic periodontitis as exposure data from the FinnGen database. Data encompassing various pregnancy stage outcomes, including pre-pregnancy conditions (irregular menstruation, endometriosis, abnormal reproductive bleeding, and female infertility), pregnancy complications (hemorrhage, spontaneous miscarriage, and abnormalities in products), and post-pregnancy factors (single spontaneous delivery, labor duration, and birth weight of the child), were obtained from the UK Biobank. The random-effects inverse-variance weighted (IVW) method was utilized to compute primary estimates while diligently assessing potential directional pleiotropy and heterogeneity. RESULTS: Our findings indicate a negative association between periodontitis and labor duration (odds ratio [OR] = 0.999; 95% confidence interval [CI]: 0.999 to 1.000; P = 0.017). Individuals with periodontitis are more likely to deliver lower-weight infants (OR = 0.983; 95% CI: 0.972 to 0.995; P = 0.005). We found no evidence of pleiotropy or heterogeneity in aforementioned two associations. We did not observe casual links with pre-pregnancy conditions and pregnancy complications. CONCLUSIONS: This Mendelian Randomization study underscores the genetic influence of periodontitis on specific adverse pregnancy outcomes, particularly concerning labor duration and lower birth weight deliveries. CLINICAL RELEVANCE: Our study emphasizes the critical importance of maintaining periodontal health during pregnancy and offers genetic evidence supporting these associations. Further investigation is required to delve deeper into the specific underlying mechanisms.
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Periodontitis Crónica , Complicaciones del Embarazo , Niño , Lactante , Embarazo , Humanos , Femenino , Peso al Nacer/genética , Análisis de la Aleatorización Mendeliana , Biobanco del Reino UnidoRESUMEN
This study aimed to estimate (co)variance components and genetic parameters for calving ease (CE) and their genetic correlations with growth, reproductive, carcass, and feed efficiency traits in Nellore cattle. Phenotypes for CE are scored in two categories: normal calving and assisted calving. The traits considered were probability of precocious calving, age at first calving, stayability, adjusted scrotal circumference at 365 days of age, accumulated cow productivity, age at puberty of males, gestation length, birth weight, adjusted weights at 210 and 450 days of age, adult cow weight, frame score, hip height, rib eye area, subcutaneous backfat thickness, rump fat thickness, intramuscular fat percentage, residual feed intake and dry matter intake. The estimation of genetic parameters was performed using a two-trait threshold-linear animal model, except for CE, stayability, and probability of precocious calving, which were evaluated through a two-trait threshold animal model. The direct (0.27) and maternal (0.19) heritability estimates for CE in heifers primiparous Nellore indicated that selecting for this trait is feasible. The selection to improve the female sexual precocity should consider CE during the selection and mating decisions to reduce calving problems. Genetic correlation estimates between CE and BW suggest that selecting low birth weight to reduce calving problems is not an appropriate strategy to improve calving ease in heifers Nellore. Therefore, adopting a multi-trait selection model with CE and BW in the Nellore breed would reduce calving difficulties, particularly in sexually precocious heifers, without impairing the growth, reproductive, feed efficiency conversion, and carcass indicator traits.
Asunto(s)
Fenotipo , Animales , Bovinos/genética , Bovinos/fisiología , Bovinos/crecimiento & desarrollo , Femenino , Embarazo , Masculino , Peso al Nacer/genética , Reproducción/genética , Cruzamiento , Paridad/genéticaRESUMEN
This study aimed to estimate two reproductive efficiency indices in sheep based on the ratio between litter weight (at birth and weaning) and dam weight, as well as their genetic parameters. Phenotypic and pedigree data comprising the period from 1990 to 2018 were obtained from the Santa Inês sheep database of Embrapa Tabuleiros Costeiros. For estimation of the genetic parameters of the indices, a repeatability model was applied in single- and two-trait analyses by a Bayesian approach. The mean reproductive efficiency index was 0.069 ± 0.0163 and 0.43 ± 0.0955 at birth and weaning, respectively. These values indicate that, on average, ewes give birth to 69 g of lamb per kg body weight and wean 430 g of lamb per kg body weight. Described here for the first time, the heritability estimate obtained in single- and two-trait analyses was 0.24 for the index based on birth weights and ranged from 0.13 to 0.15 for the index based on weaning weights. The estimates indicate the possibility of genetic gain by selection and are similar to those reported for reproductive traits in sheep, representing an option for selection criterion. The genetic correlation between indices was positive and moderate (0.26). The repeatability estimates were high (0.49 for the birth weight index and 0.71 for the weaning weight index). These values indicate good prediction of future performance with few observations. The weaning weight index might be a good culling criterion of females.