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1.
J Anim Sci ; 98(7)2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32609315

RESUMO

Data on calving ease (CE) and birth, weaning weight (WW), and yearling weight (YW) were obtained from the American Simmental Association (ASA) and included pedigree and performance information on 11,640,735 animals. Our objective was to quantify differential response from selection for high CE vs. low birth weight (LBW) in first-calf Simmental heifers. We hypothesized that direct selection for CE should be used as the primary approach to reduce dystocia and mitigate losses in growth-related traits. WW and YW were adjusted to 205 and 365 d of age, respectively. Sire and maternal grandsire (co)variance components for CE, birth weight (BW), and 205-d weaning weight (205-d WW), and sire covariance components for 160-d postweaning gain (160-d gain) were estimated using a sire-maternal grandsire model. Direct and maternal expected progeny differences (EPD) for CE, BW, and 205-d WW and direct EPD for 160-d gain and 365-d yearling weight (365-d YW) for first-calf Simmental heifers population (465,710 animals) were estimated using a threshold-linear multivariate maternal animal model. This population was used to estimate genetic trends and as a selection pool (control) for various selection scenarios. Selection scenarios were high CE (HCE), LBW, the all-purpose selection index (API = -1.8 BW + 1.3 CE + 0.10 WW + 0.20 YW) of the ASA and its two derived subindices: (API1 = 1.3 CE + 0.20 YW) and (API2 = -1.8 BW + 0.20 YW), and lastly Dickerson's selection index (DSI = -3.2 BW + YW). Data for each selection scenario were created by selecting sires with EPD greater than or equal to the average along with the top 75% of dams. Comparison between selection scenarios involved evaluating the direct and maternal genetic trends from these scenarios. Direct heritabilities for CE, BW, 205-d WW, 160-d gain, and 365-d YW of Simmental cattle were 0.23, 0.52, 0.28, 0.21, and 0.33, respectively. The single trait, HCE, selection scenario, as opposed to LBW, increased the intercept for CE by 57.7% and the slopes (P < 0.001) for BW, 205-d WW, 160-d gain, and 365-d YW by 27.9%, 37.5%, 16%, and 28%, respectively. Comparisons of various selection scenarios revealed that the CE-based selection scenarios (HCE, API, and API1) had a greater response for CE and growth traits.


Assuntos
Peso ao Nascer/genética , Bovinos/genética , Distocia/veterinária , Seleção Genética , Animais , Peso Corporal/genética , Cruzamento , Bovinos/fisiologia , Distocia/genética , Feminino , Modelos Lineares , Masculino , Gravidez , Estados Unidos
2.
Biodemography Soc Biol ; 65(3): 268-286, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32727274

RESUMO

This study examines the impact of genes associated with normal-range birth weight (2500-4500 grams) on self-rated health in mid-to-late life course. Fifty-eight previously identified genetic variants that explain the variation in the normal-range birth weight were used to construct a genetic measure of birth weight for the non-Hispanic white sample from the Health and Retirement Study. Our results show that the genetic tendency toward higher birth weight predicts better self-rated health in mid-to-late life course net of various demographic, socioeconomic, and health behavioral factors. We also examine the heterogeneous effects of birth-weight genes across birth cohorts and age groups. Moreover, to clarify the paradox that higher birth weight can predict both better self-rated health and higher BMI, we show the positive association between birth weight genes and BMI can only hold within the normal-range BMI (18 ≤ BMI < 30). Overall, these findings suggest the genetic factors underlying the normal-range birth weight can have life-courseimpacts on health.


Assuntos
Peso ao Nascer/genética , Nível de Saúde , Autorrelato/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Herança Multifatorial/genética
4.
J Anim Sci ; 98(6)2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32374831

RESUMO

Reliable single-nucleotide polymorphisms (SNP) effects from genomic best linear unbiased prediction BLUP (GBLUP) and single-step GBLUP (ssGBLUP) are needed to calculate indirect predictions (IP) for young genotyped animals and animals not included in official evaluations. Obtaining reliable SNP effects and IP requires a minimum number of animals and when a large number of genotyped animals are available, the algorithm for proven and young (APY) may be needed. Thus, the objectives of this study were to evaluate IP with an increasingly larger number of genotyped animals and to determine the minimum number of animals needed to compute reliable SNP effects and IP. Genotypes and phenotypes for birth weight, weaning weight, and postweaning gain were provided by the American Angus Association. The number of animals with phenotypes was more than 3.8 million. Genotyped animals were assigned to three cumulative year-classes: born until 2013 (N = 114,937), born until 2014 (N = 183,847), and born until 2015 (N = 280,506). A three-trait model was fitted using the APY algorithm with 19,021 core animals under two scenarios: 1) core 2013 (random sample of animals born until 2013) used for all year-classes and 2) core 2014 (random sample of animals born until 2014) used for year-class 2014 and core 2015 (random sample of animals born until 2015) used for year-class 2015. GBLUP used phenotypes from genotyped animals only, whereas ssGBLUP used all available phenotypes. SNP effects were predicted using genomic estimated breeding values (GEBV) from either all genotyped animals or only core animals. The correlations between GEBV from GBLUP and IP obtained using SNP effects from core 2013 were ≥0.99 for animals born in 2013 but as low as 0.07 for animals born in 2014 and 2015. Conversely, the correlations between GEBV from ssGBLUP and IP were ≥0.99 for animals born in all years. IP predictive abilities computed with GEBV from ssGBLUP and SNP predictions based on only core animals were as high as those based on all genotyped animals. The correlations between GEBV and IP from ssGBLUP were ≥0.76, ≥0.90, and ≥0.98 when SNP effects were computed using 2k, 5k, and 15k core animals. Suitable IP based on GEBV from GBLUP can be obtained when SNP predictions are based on an appropriate number of core animals, but a considerable decline in IP accuracy can occur in subsequent years. Conversely, IP from ssGBLUP based on large numbers of phenotypes from non-genotyped animals have persistent accuracy over time.


Assuntos
Bovinos/genética , Genótipo , Modelos Genéticos , Algoritmos , Animais , Peso ao Nascer/genética , Cruzamento , Bovinos/fisiologia , Feminino , Genoma , Genômica , Parto , Polimorfismo de Nucleotídeo Único , Gravidez , Projetos de Pesquisa , Desmame
5.
Eur J Epidemiol ; 35(7): 685-697, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32383070

RESUMO

Epidemiology studies suggested that low birthweight was associated with a higher risk of hypertension in later life. However, little is known about the causality of such associations. In our study, we evaluated the causal association of low birthweight with adulthood hypertension following a standard analytic protocol using the study-level data of 183,433 participants from 60 studies (CHARGE-BIG consortium), as well as that with blood pressure using publicly available summary-level genome-wide association data from EGG consortium of 153,781 participants, ICBP consortium and UK Biobank cohort together of 757,601 participants. We used seven SNPs as the instrumental variable in the study-level analysis and 47 SNPs in the summary-level analysis. In the study-level analyses, decreased birthweight was associated with a higher risk of hypertension in adults (the odds ratio per 1 standard deviation (SD) lower birthweight, 1.22; 95% CI 1.16 to 1.28), while no association was found between genetically instrumented birthweight and hypertension risk (instrumental odds ratio for causal effect per 1 SD lower birthweight, 0.97; 95% CI 0.68 to 1.41). Such results were consistent with that from the summary-level analyses, where the genetically determined low birthweight was not associated with blood pressure measurements either. One SD lower genetically determined birthweight was not associated with systolic blood pressure (ß = - 0.76, 95% CI - 2.45 to 1.08 mmHg), 0.06 mmHg lower diastolic blood pressure (ß = - 0.06, 95% CI - 0.93 to 0.87 mmHg), or pulse pressure (ß = - 0.65, 95% CI - 1.38 to 0.69 mmHg, all p > 0.05). Our findings suggest that the inverse association of birthweight with hypertension risk from observational studies was not supported by large Mendelian randomization analyses.


Assuntos
Peso ao Nascer , Pressão Sanguínea/genética , Hipertensão/epidemiologia , Hipertensão/genética , Análise da Randomização Mendeliana/métodos , Adulto , Peso ao Nascer/genética , Peso ao Nascer/fisiologia , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Polimorfismo de Nucleotídeo Único/genética
6.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(3): 310-314, 2020 Mar 10.
Artigo em Chinês | MEDLINE | ID: mdl-32294826

RESUMO

Objective: To quantitate the association between birth weight and phenotypes of physical indicators in adulthood, i.e. BMI and waist circumference (WC) and to what degree genetic or environmental factors affect birth weight-obesity association. Methods: A total of 6 623 gender matched twin pairs aged 25 to 79 years were recruited through the Chinese National Twin Registry. The twins reported their own birth weight, current height and weight, and WC using a self-administered questionnaire. BMI was calculated according to the self-reports of body height and weight. Within twin-pair design was used to quantitate the association between birth weight and phenotypes related to obesity while bivariate structural equation models were used to decompose the phenotype correlation. Results: After adjusted for multiple factors, twin-pair analyses within monozygotic (MZ) showed that, on average, a 1.0 kg increase in birth weight corresponded to an increase of 0.33 kg/m(2) in BMI and 0.95 cm in WC in adulthood (P<0.001). Bivariate structural equation models showed significant positive unique environmental correlation between birth weight and the two obesity-related phenotypes. Conclusion: The study supported the role of twin-specific supply line factors on relationship between birth weight and physical indicators in adulthood.


Assuntos
Peso ao Nascer , Obesidade/epidemiologia , Adulto , Idoso , Peso ao Nascer/genética , China/epidemiologia , Feminino , Interação Gene-Ambiente , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/genética , Sistema de Registros , Gêmeos
7.
Trop Anim Health Prod ; 52(3): 1023-1032, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32170649

RESUMO

Separation of autosomal and sex-linked direct additive genetic effects has significant role in sheep breeding programs. Hence, this study was conducted to determine the genetic parameters of autosomal and sex-linked effects for growth traits of Zandi sheep. The data set used in this study contained 7571 Zandi lambs, descendent of 220 sires and 1481 dams, which were collected from Zandi sheep breeding Station at Khojir, Tehran, Iran from 1992 to 2011. The fixed effects included of year (20 classes), season (winter and spring), sex (male or female), birth type (single or twin), and the age of dam (seven classes, 2-8 years old). The data were analyzed using REML methodology by WOMBAT software. In the most appropriate fitted model, based on Akaike's information criterion (AIC) and Bayesian information criterion (BIC), the values of direct autosomal heritabilities of birth weight (BW), kleiber ratio at weaning (KR), 6-month weight (6MW), and 9-month weight (9MW) were 0.12 ± 0.03, 0.29 ± 0.05, 0.14 ± 0.04, and 0.15 ± 0.04, respectively. Furthermore, weaning weight (WW), average daily gain from birth to weaning (ADG), and 12-month weight (12 MW) showed the values of 0.19 ± 0.03 and 0.22 ± 0.03, 0.13 ± 0.05 and 0.15 ± 0.03, and 0.15 ± 0.05 and 0.18 ± 0.05, respectively. Based on the best models through all traits, estimates of the direct sex-linked heritability ranged from 0.0 (WW, ADG, KR, and 6MW) to 0.02 ± 0.03 (12MW). The average of autosomal and sex-linked breeding values (BVs) of body growth traits except KR (for autosomal) and 9MW and 12MW (for sex-linked) were greater than zero. The Pearson's/Spearman's correlation coefficients varied between 0.344 and 0.599/0.30 and 0.61 for autosomal and sex-linked BVs. Direct autosomal and sex-linked additive correlations for growth traits were ranged from - 0.02 (BW-KR) to 0.98 (WW-ADG) and 0.04 (KR-9 MW) to 0.99 (WW-ADG), respectively. Our results revealed that the genetic parameters related to growth traits in Zandi sheep could be more useful in selection strategies.


Assuntos
Ovinos/crescimento & desenvolvimento , Ovinos/genética , Fatores Etários , Animais , Teorema de Bayes , Peso ao Nascer/genética , Peso Corporal/genética , Cruzamento , Feminino , Irã (Geográfico) , Masculino , Gravidez , Fatores Sexuais , Ganho de Peso/genética
8.
J Anim Sci ; 98(3)2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31955195

RESUMO

With an increase in the number of animals genotyped there has been a shift from using pedigree relationship matrices (A) to genomic ones. As the use of genomic relationship matrices (G) has increased, new methods to build or approximate G have developed. We investigated whether the way variance components are estimated should reflect these changes. We estimated variance components for maternal sow traits by solving with restricted maximum likelihood, with four methods of calculating the inverse of the relationship matrix. These methods included using just the inverse of A (A-1), combining A-1 and the direct inverse of G (HDIRECT-1), including metafounders (HMETA-1), or combining A-1 with an approximated inverse of G using the algorithm for proven and young animals (HAPY-1). There was a tendency for higher additive genetic variances and lower permanent environmental variances estimated with A-1 compared with the three H-1 methods, which supports that G-1 is better than A-1 at separating genetic and permanent environmental components, due to a better definition of the actual relationships between animals. There were limited or no differences in variance estimates between HDIRECT-1, HMETA-1, and HAPY-1. Importantly, there was limited differences in variance components, repeatability or heritability estimates between methods. Heritabilities ranged between <0.01 to 0.04 for stayability after second cycle, and farrowing rate, between 0.08 and 0.15 for litter weight variation, maximum cycle number, total number born, total number still born, and prolonged interval between weaning and first insemination, and between 0.39 and 0.44 for litter birth weight and gestation length. The limited differences in heritabilities suggest that there would be very limited changes to estimated breeding values or ranking of animals across models using the different sets of variance components. It is suggested that variance estimates continue to be made using A-1, however including G-1 is possibly more appropriate if refining the model, for traits that fit a permanent environmental effect.


Assuntos
Algoritmos , Genoma/genética , Suínos/genética , Animais , Peso ao Nascer/genética , Cruzamento , Feminino , Genótipo , Tamanho da Ninhada de Vivíparos/genética , Masculino , Parto , Linhagem , Fenótipo , Gravidez , Suínos/fisiologia , Desmame
9.
Animal ; 14(5): 899-909, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31907100

RESUMO

Lamb live weight is one of the key drivers of profitability on sheep farms. Previous studies in Ireland have estimated genetic parameters for live weight and carcass composition traits using a multi-breed population rather than on an individual breed basis. The objective of the present study was to undertake genetic analyses of three lamb live weight and two carcass composition traits pertaining to purebred Texel, Suffolk and Charollais lambs born in the Republic of Ireland between 2010 and 2017, inclusive. Traits (with lamb age range in parenthesis) considered in the analyses were: pre-weaning weight (20 to 65 days), weaning weight (66 to 120 days), post-weaning weight (121 to 180 days), muscle depth (121 to 180 days) and fat depth (121 to 180 days). After data edits, 137 402 records from 50 372 lambs across 416 flocks were analysed. Variance components were derived using animal linear mixed models separately for each breed. Fixed effects included for all traits were contemporary group, age at first lambing of the dam, parity of the dam, a gender by age of the lamb interaction and a birth type by rearing type of the lamb interaction. Random effects investigated in the pre-weaning and weaning weight analyses included animal direct additive genetic, dam maternal genetic, litter common environment, dam permanent environment and residual variances. The model of analysis for post-weaning, muscle and fat depth included an animal direct additive genetic and litter common environment effect only. Significant direct additive genetic variation existed in all cases. Direct heritability for pre-weaning weight ranged from 0.14 to 0.30 across the three breeds. Weaning weight had a direct heritability ranging from 0.17 to 0.27 and post-weaning weight had a direct heritability ranging from 0.15 to 0.27. Muscle and fat depth heritability estimates ranged from 0.21 to 0.31 and 0.15 to 0.20, respectively. Positive direct correlations were evident for all traits. Results revealed ample genetic variation among animals for the studied traits and significant differences between breeds to suggest that genetic evaluations could be conducted on a per-breed basis.


Assuntos
Cruzamento , Carneiro Doméstico , Ovinos , Animais , Peso ao Nascer/genética , Peso Corporal/genética , Feminino , Irlanda , Fenótipo , Gravidez , Ovinos/genética , Desmame
10.
Anim Genet ; 51(2): 336-340, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31960458

RESUMO

Sheep, an important source of meat, dairy products and wool, play an essential part in the global agricultural economy. Body weight and body conformation are key traits in the sheep industry; however, their underlying genetic mechanisms are poorly understood. In this study, a GWAS was implemented to identify promising genes possibly linked to birth weight (BW) and body conformation traits in neonatal sheep, using a high-throughput chip (630 K). After quality control, 277 individuals and 518 203 variants were analyzed using gemma software in a mixed linear model. A total of 48 genome-wide suggestive SNPs were obtained, of which four were associated with BW, four with withers height (WH), 11 with body length (BL) and 29 with chest girth (CG). In total, 39 genes associated with BW and body conformation traits were identified by aligning to the sheep genome (Ovis aries_v4.0), and most of them were involved in the cell cycle and body development. Promising candidate genes found included the following: FOS like 2 or AP-1 transcription factor subunit (FOSL2) for BW; potassium voltage-gated channel subfamily D member 2 (KCND2) for WH; transmembrane protein 117 (TMEM117), transforming growth factor beta induced (TGFBI), and leukocyte cell-derived chemotaxin 2 (LECT2) for BL; and trafficking kinesin protein 1 (TRAK1) and LOC101102529 for CG. These results provide cues for similar studies aiming at uncovering the genetic mechanisms underlying body development, and marker-assisted selection programs focusing on BW and body conformation traits in sheep.


Assuntos
Animais Recém-Nascidos/genética , Tamanho Corporal/genética , Peso Corporal/genética , Estudo de Associação Genômica Ampla/veterinária , Polimorfismo de Nucleotídeo Único , Carneiro Doméstico/fisiologia , Animais , Peso ao Nascer/genética , Estatura/genética , Humanos , Modelos Lineares , Modelos Genéticos , Carneiro Doméstico/genética
11.
BMC Genomics ; 20(1): 926, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801456

RESUMO

BACKGROUND: Single nucleotide polymorphism (SNP) arrays have facilitated discovery of genetic markers associated with complex traits in domestic cattle; thereby enabling modern breeding and selection programs. Genome-wide association analyses (GWAA) for growth traits were conducted on 10,837 geographically diverse U.S. Gelbvieh cattle using a union set of 856,527 imputed SNPs. Birth weight (BW), weaning weight (WW), and yearling weight (YW) were analyzed using GEMMA and EMMAX (via imputed genotypes). Genotype-by-environment (GxE) interactions were also investigated. RESULTS: GEMMA and EMMAX produced moderate marker-based heritability estimates that were similar for BW (0.36-0.37, SE = 0.02-0.06), WW (0.27-0.29, SE = 0.01), and YW (0.39-0.41, SE = 0.01-0.02). GWAA using 856K imputed SNPs (GEMMA; EMMAX) revealed common positional candidate genes underlying pleiotropic QTL for Gelbvieh growth traits on BTA6, BTA7, BTA14, and BTA20. The estimated proportion of phenotypic variance explained (PVE) by the lead SNP defining these QTL (EMMAX) was larger and most similar for BW and YW, and smaller for WW. Collectively, GWAAs (GEMMA; EMMAX) produced a highly concordant set of BW, WW, and YW QTL that met a nominal significance level (P ≤ 1e-05), with prioritization of common positional candidate genes; including genes previously associated with stature, feed efficiency, and growth traits (i.e., PLAG1, NCAPG, LCORL, ARRDC3, STC2). Genotype-by-environment QTL were not consistent among traits at the nominal significance threshold (P ≤ 1e-05); although some shared QTL were apparent at less stringent significance thresholds (i.e., P ≤ 2e-05). CONCLUSIONS: Pleiotropic QTL for growth traits were detected on BTA6, BTA7, BTA14, and BTA20 for U.S. Gelbvieh beef cattle. Seven QTL detected for Gelbvieh growth traits were also recently detected for feed efficiency and growth traits in U.S. Angus, SimAngus, and Hereford cattle. Marker-based heritability estimates and the detection of pleiotropic QTL segregating in multiple breeds support the implementation of multiple-breed genomic selection.


Assuntos
Peso ao Nascer/genética , Estudo de Associação Genômica Ampla/veterinária , Análise de Sequência com Séries de Oligonucleotídeos/veterinária , Locos de Características Quantitativas , Animais , Bovinos , Interação Gene-Ambiente , Polimorfismo de Nucleotídeo Único , Característica Quantitativa Herdável , Especificidade da Espécie , Desmame
12.
Clin Epigenetics ; 11(1): 194, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842976

RESUMO

BACKGROUND: Differences between an individual's estimated epigenetic gestational age (EGA) and their actual gestational age (GA) are defined as gestational age acceleration (GAA). GAA is associated with increased birthweight and birth length. Whether these associations persist through childhood is yet to be investigated. METHODS: We examined the association between GAA and trajectories of height and weight from birth to 10 years (n = 785) in a British birth cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC). EGA of participants was estimated using DNA methylation data from cord blood using a recently developed prediction model. GAA of participants, measured in weeks, was calculated as the residuals from a regression model of EGA on actual GA. Analyses were performed using linear spline multilevel models and adjusted for maternal age, maternal pre-pregnancy BMI, maternal smoking during pregnancy, and maternal education. RESULTS: In adjusted analyses, offspring with a one-week greater GAA were born on average 0.14 kg heavier (95% confidence interval (CI) 0.09, 0.19) and 0.55 cm taller (95% CI 0.33, 0.78) at birth. These differences in weight persisted up to approximately age 9 months but thereafter began to attenuate. From age 5 years onwards, the association between GAA and weight reversed such that GAA was associated with lower weight and this association strengthened with age (mean difference at age 10 years - 0.60 kg, 95% CI - 1.19, - 0.01). Differences in height persisted only up to age 9 months (mean difference at 9 months 0.15 cm, 95% CI - 0.09, 0.39). From age 9 months to age 10 years, offspring with a one-week greater GAA were of comparable height with those with no GAA (mean difference at age 10 years - 0.07 cm, 95% CI - 0.64, 0.50). CONCLUSIONS: Gestational age acceleration is associated with increased birth weight and length and these differences persist to age 9 months. From age 5 years onwards, the association of GAA and weight reverses such that by age 10 years, greater GAA is associated with lower childhood weight. Further work is required to examine whether the weight effects of GAA strengthen through adolescence and into early adulthood.


Assuntos
Peso ao Nascer/genética , Estatura/genética , Metilação de DNA , Sangue Fetal/química , Criança , Pré-Escolar , Epigênese Genética , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Idade Materna , Estudos Prospectivos
13.
Environ Health ; 18(1): 100, 2019 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752878

RESUMO

BACKGROUND: Increasing evidence suggests that prenatal exposure to arsenic, even at common environmental levels, adversely affects child health. These adverse effects include impaired fetal growth, which can carry serious health implications lifelong. However, the mechanisms by which arsenic affects fetal health and development remain unclear. METHODS: We addressed this question using a group of 46 pregnant women selected from the New Hampshire Birth Cohort Study (NHBCS), a US cohort exposed to low-to-moderate arsenic levels in drinking water through the use of unregulated private wells. Prenatal arsenic exposure was assessed using maternal urine samples taken at mid-gestation. Samples of the fetal portion of the placenta were taken from the base of the umbilical cord insertion at the time of delivery, stored in RNAlater and frozen. We used RNA sequencing to analyze changes in global gene expression in the fetal placenta associated with in utero arsenic exposure, adjusting for maternal age. Gene set enrichment analysis and enrichment mapping were then used to identify biological processes represented by the differentially expressed genes. Since our previous analyses have identified considerable sex differences in placental gene expression associated with arsenic exposure, we analyzed male and female samples separately. RESULTS: At FDR < 0.05, no genes were differentially expressed in female placenta, while 606 genes were differentially expressed in males. Genes showing the most significant associations with arsenic exposure in females were LEMD1 and UPK3B (fold changes 2.51 and 2.48), and in males, FIBIN and RANBP3L (fold changes 0.14 and 0.15). In gene set enrichment analyses, at FDR < 0.05, a total of 211 gene sets were enriched with differentially expressed genes in female placenta, and 154 in male placenta. In female but not male placenta, 103 of these gene sets were also associated with reduced birth weight. CONCLUSIONS: Our results reveal multiple biological functions in the fetal placenta that are potentially affected by increased arsenic exposure, a subset of which is sex-dependent. Further, our data suggest that in female infants, the mechanisms underlying the arsenic-induced reduction of birth weight may involve activation of stress response pathways.


Assuntos
Arsênico/efeitos adversos , Peso ao Nascer/efeitos dos fármacos , Exposição Materna/efeitos adversos , Placenta/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Poluentes Químicos da Água/efeitos adversos , Adulto , Peso ao Nascer/genética , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Masculino , New Hampshire , Placenta/metabolismo , Gravidez , Fatores Sexuais
14.
BMC Vet Res ; 15(1): 395, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694632

RESUMO

BACKGROUND: Weight at birth is an important predictor of neonatal mortality and morbidity in dogs. In addition, the birthweight of the puppies in a litter influences the decision to perform a cesarean section. The goal of the present study was to estimate heritabilities for the puppy birth weight in Labrador retrievers. RESULTS: Of the 1138 Labrador retriever litters whelped at the Guiding Eye for the Blind between September 2001 and February 2018, 1013 were included in the analyses after data editing. Puppy weight at birth was the target trait, measured on a continuous scale in pounds, and converted to grams. Linear mixed models were used to identify factors influencing puppy weight at birth. The analyses showed that the sex of the puppy, litter size, length of gestation, adult weight of the dam, parity, year of birth and inbreeding coefficient of the puppies and dams contributed to the variance of the puppy birth weight. Dam and litter effects were included as random effects. A multiple trait derivative free restricted maximum likelihood approach was used to estimate variance components and genetic parameters with two animal models, one without covariates (Model 1) and one with covariates (Model 2). Sex of the puppy and litter size had moderate effects, whereas gestation length, adult weight of the dam, parity, year of birth and inbreeding coefficients of the dam and the puppies had minor effects. Estimates for Model 1 and Model 2 were 0.21 and 0.17 for the direct heritabilities, 0.22 and 0.22 for the maternal additive genetic heritabilities, 0.07 and 0.07 for the maternal permanent environmental proportions, and 0.14 and 0.08 for the environmental proportion of the litter. CONCLUSIONS: In order to estimate reliable breeding values for puppy weight at birth, sex of puppy, litter size, length of gestation and the adult weight of the dam should be included. Estimates could benefit from weighing the dams prior to each mating.


Assuntos
Animais Recém-Nascidos/genética , Peso ao Nascer/genética , Cães/genética , Animais , Animais Recém-Nascidos/fisiologia , Peso ao Nascer/fisiologia , Feminino , Idade Gestacional , Endogamia , Modelos Lineares , Tamanho da Ninhada de Vivíparos , Masculino , Paridade , Gravidez
15.
Nat Commun ; 10(1): 5086, 2019 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-31704910

RESUMO

Accurate prediction of an individual's phenotype from their DNA sequence is one of the great promises of genomics and precision medicine. We extend a powerful individual-level data Bayesian multiple regression model (BayesR) to one that utilises summary statistics from genome-wide association studies (GWAS), SBayesR. In simulation and cross-validation using 12 real traits and 1.1 million variants on 350,000 individuals from the UK Biobank, SBayesR improves prediction accuracy relative to commonly used state-of-the-art summary statistics methods at a fraction of the computational resources. Furthermore, using summary statistics for variants from the largest GWAS meta-analysis (n ≈ 700, 000) on height and BMI, we show that on average across traits and two independent data sets that SBayesR improves prediction R2 by 5.2% relative to LDpred and by 26.5% relative to clumping and p value thresholding.


Assuntos
Teorema de Bayes , Herança Multifatorial/genética , Análise de Regressão , Tecido Adiposo , Alopecia/genética , Metabolismo Basal/genética , Bancos de Espécimes Biológicos , Peso ao Nascer/genética , Composição Corporal/genética , Estatura/genética , Índice de Massa Corporal , Densidade Óssea/genética , Diabetes Mellitus Tipo 2/genética , Volume Expiratório Forçado/genética , Estudos de Associação Genética , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único , Estatística como Assunto , Capacidade Vital/genética , Relação Cintura-Quadril
16.
Anim Sci J ; 90(12): 1510-1516, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31625251

RESUMO

We estimated genetic parameters in Landrace and Large White pig populations for litter traits at farrowing (total number born, number born alive, number stillborn, total litter weight at birth (LWB), and mean litter weight at birth) and those at weaning (litter size at weaning (LSW), total litter weight at weaning (LWW), mean litter weight at weaning (MWW), and survival rate from farrowing to weaning). We analyzed 65,579 records at farrowing and 6,306 at weaning for Landrace, and 52,557 and 5,360, respectively, for Large White. Single-trait and two-trait repeatability animal models were exploited to estimate heritability and genetic correlation respectively. Heritability estimates of LSW were 0.09 for Landrace and 0.08 for Large White. Genetic correlations of LSW with MWW were -0.43 for Landrace and -0.24 for Large White. Genetic correlations of LSW with LWW and LWB ranged from 0.5 to 0.6. The genetic correlation of MWW with LWW was positive, but that with LWB was negligible. The results indicate that utilizing LWW or LWB could improve LSW efficiently, despite the antagonistic genetic correlation between LSW and MWW.


Assuntos
Reprodução/genética , Suínos , Animais , Peso ao Nascer/genética , Peso Corporal/genética , Feminino , Hereditariedade/genética , Tamanho da Ninhada de Vivíparos/genética , Parto , Fenótipo , Gravidez , Natimorto/genética , Análise de Sobrevida , Desmame
17.
Am J Epidemiol ; 188(11): 1887-1889, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31647097

RESUMO

A substantial body of literature has shown robust associations between prenatal smoking exposure and DNA methylation levels. The pattern of DNA methylation can be used as a molecular signature of past prenatal smoking exposure and might also provide mechanistic insights into associations between prenatal smoking exposure and adverse health outcomes. In this issue of the Journal, Cardenas et al. (Am J Epidemiol. 2019;188(11):1878-1886) evaluated whether DNA methylation mediates the association between prenatal smoking and low birth weight in a tissue that is mechanistically relevant to birth weight-the placenta-using formal mediation analyses. They found that methylation levels, at 5 loci, mediated smoking exposure effects on birth weight but only among children whose mothers smoked during pregnancy. Given the use of formal mediation methods and measurement in a mechanistically relevant tissue, this work has the potential to inform novel directions for intervention. Replication of these findings in larger and more racially and ethnically diverse samples, repeated measures to better tease apart the timing of DNA methylation changes with respect to exposure and birth weight, and continued use of intervention-focused mediation methods are needed before the impact of these findings will be fully realized.


Assuntos
Metilação de DNA , Efeitos Tardios da Exposição Pré-Natal , Peso ao Nascer/genética , Criança , Saúde da Criança , Feminino , Humanos , Placenta , Gravidez , Fumar
18.
Diabetes Res Clin Pract ; 157: 107876, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31586661

RESUMO

AIMS: To assess outcomes of women in the Pregnancy and Neonatal Diabetes Outcomes in Remote Australia (PANDORA) cohort with gestational diabetes mellitus (GDM) managed by lifestyle modification compared with women without hyperglycaemia in pregnancy. METHODS: Indigenous (n = 97) and Europid (n = 113) women managed by lifestyle modification were compared to women without hyperglycaemia (n = 235). Multivariate linear and logistic regressions assessed whether GDM-lifestyle women had poorer outcomes compared to women without hyperglycaemia. RESULTS: Women with GDM-lifestyle had higher body mass index and lower gestational weight gain than women without hyperglycaemia. On univariate analysis, gestational age at delivery was lower and induction rates were higher in women with GDM-lifestyle than without hyperglycaemia. On multivariable regression, GDM-lifestyle was associated with lower gestational age at delivery (by 0.73 weeks), lower birthweight z-score (by 0.26, p = 0.007), lower likelihood of large for gestational age (LGA) [OR (95% CI): 0.55 (0.28, 1.02), p = 0.059], and greater likelihood of labour induction [2.34 (1.49, 3.66), p < 0.001] than women without hyperglycaemia. CONCLUSION: Women with GDM managed by lifestyle modification had higher induction rates and their offspring had lower birthweight z-scores, with a trend to lower LGA than those without hyperglycaemia in pregnancy. Further studies are indicated to explore reasons for higher induction rates.


Assuntos
Peso ao Nascer/genética , Diabetes Gestacional/terapia , Estilo de Vida , Complicações na Gravidez/terapia , Adolescente , Adulto , Feminino , Humanos , Gravidez , Adulto Jovem
19.
PLoS One ; 14(9): e0222141, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31504067

RESUMO

BACKGROUND: Lower birth weight is associated with diabetes although the underlying mechanisms are unclear. Muscle mass could be a modifiable link and hence a target of intervention. We assessed the associations of birth weight with muscle and fat mass observationally in a population with little socio-economic patterning of birth weight and using Mendelian randomization (MR) for validation. METHODS: In the population-representative "Children of 1997" birth cohort (n = 8,327), we used multivariable linear regression to assess the adjusted associations of birth weight (kg) with muscle mass (kg) and body fat (%) at ~17.5 years. Genetically predicted birth weight (effect size) was applied to summary genetic associations with fat-free mass and fat mass (kg) from the UK Biobank (n = ~331,000) to obtain unconfounded estimates using inverse-variance weighting. RESULTS: Observationally, birth weight was positively associated with muscle mass (3.29 kg per kg birth weight, 95% confidence interval (CI) 2.83 to 3.75) and body fat (1.09% per kg birth weight, 95% CI 0.54 to 1.65). Stronger associations with muscle mass were observed in boys than in girls (p for interaction 0.004). Using MR, birth weight was positively associated with fat-free mass (0.77 kg per birth weight z-score, 95% CI 0.22 to 1.33) and fat mass (0.58, 95% CI 0.01 to 1.15). No difference by sex was evident. CONCLUSION: Higher birth weight increasing muscle mass may be relevant to lower birth weight increasing the risk of diabetes and suggests post-natal muscle mass as a potential target of intervention.


Assuntos
Peso ao Nascer/genética , Composição Corporal/genética , China , Feminino , Humanos , Recém-Nascido , Masculino , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único
20.
Cancer Epidemiol ; 62: 101564, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31325768

RESUMO

BACKGROUND: The aetiology of thyroid cancer is poorly understood, but it is possible that this malignancy has origins early in life. It is, however, currently unknown if birthweight, as an indicator of prenatal growth, is related to thyroid cancer risk. OBJECTIVE: To investigate if birthweight is associated with the later risk of thyroid cancer and its histological types. METHODS: 246,141 children (120,505 girls, 125,636 boys) from the Copenhagen School Health Records Register, born 1936-1989, were prospectively followed in the Danish Cancer Registry. Cox regressions were used to estimate hazards ratios (HR) and 95% confidence intervals (CI). RESULTS: During follow up, 241 individuals (172 women, 69 men) were diagnosed with thyroid cancer (162 papillary, 53 follicular). Birthweight was significantly and positively associated with risk of thyroid cancer overall (HR = 1.30 [95% CI: 1.03-1.64] per kilogram). There were no sex differences in the associations. Birthweight was positively and significantly associated with follicular thyroid cancer (HR = 1.74 [95% CI: 1.07-2.82] per kilogram), and although there was an indication of a positive association, it did not reach statistical significance for the more common papillary type (HR = 1.20 [95% CI: 0.90-1.59] per kilogram). CONCLUSION: A heavier weight at birth is associated with an elevated risk of total and follicular thyroid cancer, which underscores that prenatal exposures may be important in thyroid cancer aetiology.


Assuntos
Peso ao Nascer/genética , Neoplasias da Glândula Tireoide/epidemiologia , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Fatores de Risco , Neoplasias da Glândula Tireoide/patologia , Adulto Jovem
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