Paternal Heritability Research Articles

Cardiovascular Events According To Maternal Or Paternal Heritability Of Genetic Mutation In Familial Hypercholesterolemia

Familial hypercholesterolemia (FH) is a genetic autosomal disease, characterized by high levels of cholesterol since birth, that leads to a very high cardiovascular (CV) risk. In patients with the heterozygous FH (HeFH), in case of a maternal transmission, fetus is exposed to high maternal cholesterol levels during pregnancy. Based on the Developmental Origins of Health and Disease concept, our objective was to study the effect of heritability of genetic FH mutation on the occurrence of CV events in adults with HeFH. We included 138 HeHF patients with a genetic diagnosis and a clear familial history of hypercholesterolemia among 513 patients included in the Marseille's REFERCHOL register. Occurrence of CV events were compared by maternal (MH group, 64 patients) or paternal (PH group, 74 patients) heritability. The logistic regression method was used to determine the predictors of CV events. At inclusion, parameters were comparable between groups except more hypertension (25% vs. 9.4%, P = 0.01), more treatment by anti-PCSK9 (20.3 vs. 5.4%, P = 0.008) and less familial early CV events (28.6 vs. 51.4%, P = 0.007) in the MH group. Regarding CV events, 35.9% of MH patients and 27% of PH patients had a CV event ( P = 0.26). Predictive factors of CV event were sex ( P = 0.0004), age at start of statins ( P = 0.0003), maximal LDL-c ( P = 0.009) and Lp(a) ( P = 0.007). On multivariate analysis, heritability was not statistically associated with CV risk (PH risk vs. MH risk: OR = 0.34, P = 0.076). Sex, age at start of statins and Lp(a) were still associated with CV events occurrence (OR = 0.3, P = 0.044 for female; OR = 1.08, P = 0.001 for a later start of statins; OR = 6.98, P = 0.0096 for Lp(a)). Heritability has no significant effect on the occurrence of CV event during adulthood although paternal heritability seems to be protective. We are recruiting all HeFH patients from French FH register to improve the power of the study and confirm the observed trend.

Genetic parameters of growth traits and carcass weight of New Zealand white rabbits in a tropical dry forest area

Objective:The objective of this study was to estimate the heritability (h2), repeatability (r), and correlations (rŷiyi) in some traits of zootechnical interest in a population of New Zealand white rabbits of a tropical dry forest area.Materials and Methods:Three mating groups were formed, each one of 1 male and 70 females. The traits evaluated were litter size at birth (LB), born alive (BA), born dead (BD), litter weight born alive (LW), litter weight at weaning (LWW), weaning weight (WW), slaughter weight (SW), and carcass weight (CW). Weaning took place at 42 days, and the fattening phase lasted 60 ± 3 days. A descriptive statistical study was carried out on the study variables. Paternal heritability was estimated (hf2) and maternal (hm2), repeatability, rabbit index IC, and Pearson’s correlations (rŷiyi) between traits. The descriptive statistics showed high variation for the BD traits.Results:The values of the productivity found were similar to those presented in studies around the world. h2 presented magnitudes between low and medium. hf2 ranged between 0.09 and 0.42 and between 0.11 and 0.45 for hm2. In general, the values of hm2 were higher than the values of hf2. The r values for the traits LB, BA, LW, LWW, and SW presented low magnitude, while it was medium for WW and CW. From the values of r, IC was calculated for each of the rabbits, allowing their categorization, which will be used in future selection plans. rŷiyi among the variables ranged from −0.01 to 0.860. They were generally positive and mostly not significant (p > 0.05); they took a magnitude from low to moderate, except for the correlation between LB and BA.Conclusion:The production of rabbits under tropical conditions is similar to other reports. The genetic parameters evaluated were medium-to-low, indicating a robust non-additive gene and/or environmental effect.

Estimation of Parent-Sib Correlations for Quantitative Traits Using the Linear Mixed Regression Model: Applications to Arterial Blood Pressures Data Collected From Nuclear Families

A fundamental question in quantitative genetics is whether observed variation in the phenotypic values of a particular trait is due to environmental or to biological factors. Proportion of variations attributed to genetic factors is known as heritability of the trait. Heritability is a concept that summarizes how much of the variation in a trait is due to variation in genetic factors. Often, this term is used in reference to the resemblance between parents and their offspring. In this context, high heritability implies a strong resemblance between parents and offspring with regard to a specific trait, while low heritability implies a low level of resemblance. While many applications measure the offspring resemblance to their parents using the mid-parental value of a quantitative trait of interest as an input parameter, others focus on estimating maternal and paternal heritability. In this paper we address the problem of estimating parental heritability using the nuclear family as a unit of analysis. We derive moment and maximum likelihood estimators of parental heritability, and test their equality using the likelihood ratio test, the delta method. We also use Fieller’s interval on the ratio of parental heritability to address the question of bioequivalence. The methods are illustrated on published arterial blood pressures data collected from nuclear families.

Pubertal Onset in Boys and Girls Is Influenced by Pubertal Timing of Both Parents.

Epidemiological evidence on maternal and paternal heritability of the wide normal variation within pubertal timing is sparse. We aimed to estimate the impact of parental pubertal timing on the onset of puberty in boys and girls. Annual pubertal examinations of healthy children in a longitudinal cohort study. Information on parental timing of puberty (earlier, comparable to, or later compared to peers) and menarche age was retrieved from questionnaires. A total of 672 girls and 846 boys. Age at onset of pubic hair (PH2+), breasts (B2+), and menarche in girls; and PH2+, genital stage (G2+), and testis >3 mL with orchidometer (Tvol3+) in boys. In boys, pubertal onset was significantly associated with pubertal timing of both parents. PH2+ and Tvol3+ were earlier: -11.8 months (95% confidence interval, -16.8, -6.8)/-8.9 (-12.8, -4.9), and -9.5 (-13.9, -5.1)/-7.1 (-10.4, -3.7) if the father/mother, respectively, had early pubertal development compared to late. In girls, menarche was significantly associated with both parents' pubertal timing: -10.5 months (-15.9, -5.1)/-10.1 (-14.3, -6.0) if father/mother had early pubertal development compared to late. For the onset of PH2+ and B2+ in girls, estimates were -7.0 months (-12.6, -1.4) and -4.1 (-10.6, +2.4)/-6.7 (-11.0, -2.5), and -6.7 (-11.0, -2.0) for fathers/mothers, respectively. Maternal age of menarche was significantly associated with the onset of all pubertal milestones except PH2+ in girls. Maternal as well as paternal pubertal timing was a strong determinant of age at pubertal onset in both girls and boys. Age at breast and pubic hair development in girls, which has declined most during recent years, seemed to be least dependent on heritability.

Potential role of maternal lineage in the thoroughbred breeding strategy.

Many studies have focused on identifying the genes or single nucleotide polymorphisms associated with the athletic ability of thoroughbreds, but few have considered differences in maternal and paternal heritability of athletic ability. Herein, we report on our association study of career race performances of 675 Australian thoroughbreds with their pedigrees. Racing performance data (prize money per start) were collected from the Bloodhound database. The performance of all horses was categorised as either poor or elite athletic achievement. Then, 675 foals were divided by their parents' performance (elite or poor) into four groups: (1) elite dams and elite sires; (2) elite dams and poor sires; (3) poor dams and elite sires; and (4) poor dams and poor sires. The performance of foals was then compared between the four groups. The results show that the heritability of race performance between dams and foals (r = 0.141, P < 0.001) is much higher than that between sires and foals (r = 0.035, P = 0.366), and that this difference is statistically significant (P < 0.05). We also examined the effect of the child-bearing age of dams and sires on the ratio of elite foals. We found a strong correlation between the number of elite foals and dams' child-bearing age (r = -0.105, P < 0.001), with the ratio of elite offspring reaching a high level between a child-bearing age of 8 and 11 years (χ2 = 14.31, d.f. = 1, P < 0.001). These findings suggest that the maternal line may play an important role in the selective breeding of athletic performance in thoroughbreds.

What is new in familial hypercholesterolemia?

The purpose of this review is to describe advances in the diagnosis, cause, metabolism, risk factors for atherosclerosis, and treatment of familial hypercholesterolemia. Heterozygous familial hypercholesterolemia is almost four-fold more frequent than previously thought and is associated with 10-fold to 13-fold risk of cardiovascular disease comparing with normolipidemics. LDL receptor (LDLR) dysfunction and LDL-cholesterol (LDL-C) accumulation disturb the metabolism of other lipoprotein classes, such as chylomicrons and remnants and HDL. Next-generation sequencing can improve familial hypercholesterolemia molecular diagnosis due to its better performance and lower costs than usual techniques. Despite this, roughly 40% of familial hypercholesterolemia patients do not present mutations on the LDLR, apolipoprotein B, or proprotein convertase subtilisin/kexin type 9 genes. Many individuals with familial hypercholesterolemia phenotype have polygenic instead of monogenic cause of their elevated LDL-C concentrations. Individuals with familial hypercholesterolemia show elevated burden of subclinical atherosclerosis. The intensity of atherosclerosis burden is associated with the severity of LDLR mutation rather than maternal or paternal heritability. Newer-approved and on-development medications that reduce LDL-C hold promise for preventing cardiovascular disease in familial hypercholesterolemia. Familial hypercholesterolemia is frequent and currently underdiagnosed and undertreated, but effective cascade screening programs and early and intensive LDL-C lowering can change this picture and the natural history of the disease.

Parent-of-origin effects on glucose homeostasis in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a highly heritable complex trait. Parents of affected women have reproductive and metabolic phenotypes. We tested the hypothesis that there are parental effects on the heritability of fasting dysglycemia in women with PCOS. This was a cross-sectional study at an academic medical center. PARTICIPANTS included 367 women with PCOS and their parents (1101 total subjects). We compared maternal and paternal contributions to heritability of fasting dysglycemia and to transmission of the PCOS susceptibility allele of D19S884 within the fibrillin-3 gene (D19S884-A8) on fasting dysglycemia. Fathers had higher fasting glucose levels, prevalence of fasting dysglycemia and proinsulin to insulin molar ratios (P < .0001), a marker of defective insulin processing, compared with mothers. Heritability of fasting dysglycemia was significant in PCOS families (h(2) = 37%, SE = 10%, P = .001). Maternal heritability (h(2) = 51%, SE = 15%, P = .0009) was higher than paternal heritability (h(2) = 23 %, SE = 23%, P = .186) of fasting dysglycemia after adjustment for age and body mass index. Within dysglycemic probands, there was increased maternal compared with paternal transmission of D19S884-A8 (maternal 84% vs paternal 45%, χ(2) = 6.51, P = .011). There was a sex difference in the parental metabolic phenotype with fathers having an increased risk of fasting dysglycemia and evidence for pancreatic β-cell dysfunction compared with mothers. However, only maternal heritability had significant effects on the prevalence of fasting dysglycemia in women with PCOS. Furthermore, there were maternal parent-of-origin effects on transmission of D19S884-A8 probands with fasting dysglycemia. These findings suggest that maternal factors, genetic and perhaps epigenetic, contribute to the metabolic phenotype in affected women.

Bone Mass and Bone Size in Pre- or Early Pubertal 10-Year-Old Black and White South African Children and Their Parents

Genetic factors are thought to maintain bone mass in socioeconomically disadvantaged black South Africans. We compared bone mass between environmentally disadvantaged black and advantaged white children and their parents, after determining the most appropriate method by which to correct bone mineral content (BMC) for size. We collected data from 419 healthy black and white children of mean age 10.6 years (range 10.0-10.9), 406 biological mothers, and 100 biological fathers. Whole-body, femoral neck, lumbar spine, and mid- and distal one-third of radius bone area (BA) and BMC were measured by dual-energy X-ray absorptiometry. Power coefficients (PCs) were calculated from the linear-regression analyses of ln(BMC) on ln(BA) and used to correct site-specific BMC for bone size differences. Heritability (½h(2), %) by maternal and paternal descent was estimated by regressing children's Z scores on parents' Z scores. Correcting BMC for height, weight, and BA(PC) accounted for the greatest variance of BMC at all skeletal sites. In so doing, BMC in blacks was up to 2.6 times greater at the femoral neck and lumbar spine. Maternal and paternal heritability was estimated to be ~30% in both black and white subjects. These results may in part explain the lower prevalence of fragility fractures at the hip in black South African children when compared to whites. Heritability was comparable between environmentally disadvantaged black and advantaged white South African children and similar to that reported for Caucasians in other parts of the world.

Genetic Variation of the Ghrelin Signaling System in Females With Severe Alcohol Dependence

Central ghrelin signaling is required for the rewarding effects of alcohol in mice. Because ghrelin is implied in other addictive behaviors such as eating disorders and smoking, and because there is co-morbidity between these disorders and alcohol dependence, the ghrelin signaling system could be involved in mediating reward in general. Furthermore, in humans, single nucleotide polymorphisms (SNPs) and haplotypes of the pro-ghrelin gene (GHRL) and the ghrelin receptor gene (GHSR) have previously been associated with increased alcohol consumption and increased body weight. Known gender differences in plasma ghrelin levels prompted us to investigate genetic variation of the ghrelin signaling system in females with severe alcohol dependence (n = 113) and in a selected control sample of female low-consumers of alcohol from a large cohort study in southwest Sweden (n = 212). Six tag SNPs in the GHRL (rs696217, rs3491141, rs4684677, rs35680, rs42451, and rs26802) and four tag SNPs in the GHSR (rs495225, rs2232165, rs572169, and rs2948694) were genotyped in all individuals. We found that one GHRL haplotype was associated with reports of paternal alcohol dependence as well as with reports of withdrawal symptoms in the female alcohol-dependent group. Associations with 2 GHSR haplotypes and smoking were also shown. One of these haplotypes was also negatively associated with BMI in controls, while another haplotype was associated with having the early-onset, more heredity-driven, type 2 form of alcohol dependence in the patient group. Taken together, the genes encoding the ghrelin signaling system cannot be regarded as major susceptibility genes for female alcohol dependence, but is, however, involved in paternal heritability and may affect other reward- and energy-related factors such as smoking and BMI.

Heritability of parturition timing: an extended twin design analysis

The objective of the study was to assess relative maternal and paternal genetic influences on birth timing. Utilizing The Netherlands Twin Registry, we examined the correlation in birth timing of infants born to monozygotic (MZ) twins and their first-degree relatives (dizygotic twins and siblings of twins). Genetic models estimated the relative influence of genetic and common environmental factors through model fitting of additive genetic (A), common environmental (C), individual-specific environmental factors, and combinations thereof. We evaluated birth timing correlation among the infants of 1390 twins and their 644 siblings. The correlation in MZ female twins (r = 0.330) was greater than MZ male twins (r = -0.096). Positive correlation were also found in sister-sister pairs (r = 0.223) but not in brother-brother (r = -0.045) or brother-sister pairs (r = -0.038). The most parsimonious AE model indicated a significant maternal contribution of genetic and individual-specific environmental factors to birth timing, but no paternal heritability was demonstrated. Heritability of birth timing in women was 34%; and the remaining variance (66%) was caused by individual-specific environmental factors. Our data implicate a significant contribution of maternal but not paternal genetic influences on birth timing.

Estimation of genetic parameters for litter size as a sow and boar trait in German herdbook Landrace and Pietrain swine

Variance components for number of pigs born alive (NBA) were estimated by Gibbs Sampling using an animal model for the additive genetic maternal and paternal effect. The analysis was based on 48,577 litter records of German Landrace (DL) and 23,003 litter records of Pietrain (PI) herdbook sows. All data sets were provided by the official performance recording organization in Bavaria. The variance components for NBA were estimated in a bivariate animal model for first parity sows and sows with parities 2 to 10 taking into account the fixed effects of herd-year-season and parity number. Permanent environment of the sow and the paternal and maternal additive genetic effects were modelled as randomly distributed effects. The estimate for paternal heritability in both breeds was h 2 p=0.05 in parity number 1 and h 2 p=0.03 in parity numbers 2–10. The corresponding estimates for maternal heritability were h 2 m=0.15 in parity number 1 in both breeds and h 2 m=0.11 (DL) and h 2 m=0.09 (PI) in parity numbers 2–10. Genetic correlations between paternal and maternal additive genetic effects were positive and in the range from r pm=0.01 to r pm=0.25. Genetic correlations between paternal additive genetic effects in different parities were of medium size at r pp=0.47 for DL and r pp=0.34 for PI. This study confirms the additive genetic influence of a paternal component on NBA, in addition to the maternal component.

Variance components of fertility in Spanish Landrace pigs

Fertility is a discrete trait with two categories (1, successful mating, 0, unsuccessful mating). A Bayesian analysis with a binary threshold animal model has been performed with 18 695 AI mating records from 1987 to 1997, concerning 4085 sows and 187 boars. The pedigree included all individuals genetically linked with data. The binary response was modeled under a probit approach. The model for liability includes paternal and maternal genetic and permanent environmental effects, 54 herd-year–season and seven order of parity effects. Posterior mean (and standard deviation) for paternal heritability was 0.028 (0.014), for maternal heritability 0.038 (0.014), and 0.028 (0.009) and 0.072 (0.017) for ratios of paternal and maternal permanent environmental effects. Posterior mean (and standard deviation) of genetic correlation between paternal and maternal genetic effects was −0.513 (0.264). Differences between parities suggest that fertility is bigger in second parity than in the first one, and decrease in subsequent parities.