Genetic correlation between the ages of menarche and menopause

Using mostly prospective menstrual data from mothers and daughters in the Tremin Trust Menstrual Reproductive History Program, this study produces the first estimates of the genetic correlation between the ages of menarche and menopause. I carried out two separate analyses. Standard regression analysis of 21 mother/daughter dyads with natural menopause yielded a nonsignificant negative mean genetic correlation of r _A =−0.139±1.268. Survival analysis/maximum likelihood estimation on a dataset which included an additional 85 dyads with censored observations on daughters (N=106) yielded a nonsignificant positive genetic correlation of r _A =0.613±0.587 (p=0.1492). Although a substantial non-zero correlation cannot be ruled out, these estimates suggest there is no genetic correlation between menarche and menopause, in agreement with previous phenotypic findings. As inconclusive as they may be, these estimates also contribute to our understanding of the nature of selection working on the reproductive life span of human females.     

The effects of high altitude on age at menarche and menopause

The age at menarche and menopause of three groups of Bhotia females living at high altitude, Himalayan region — Uttar Pradesh, North India, were studied. The Johari Bhotia women had earliest menarche (¯X=15.1±1.1 years) as compared to Rang Bhotias, settled (¯X=15.6±0.9 years) and Rang Bhotias, migratory (¯X=16.0±1.0 years). The differences between all these three groups for age at menarche were significant. A trend towards increase in age at menarche with an increase in altitude has been observed, but the total fertility period in the three groups remained similar as early menarche has been found to be associated with early onset of menopause and late menarche with late menopause.     

A large-scale candidate gene association study of age at menarche and age at natural menopause

Recent genome-wide association (GWA) studies have identified several novel genetic loci associated with age at menarche and age at natural menopause. However, the stringent significance threshold used in GWA studies potentially led to false negatives and true associations may have been overlooked. Incorporating biologically relevant information, we examined whether common genetic polymorphisms in candidate genes of nine groups of biologically plausible pathways and related phenotypes are associated with age at menarche and age at natural menopause. A total of 18,862 genotyped and imputed single nucleotide polymorphisms (SNPs) in 278 genes were assessed for their associations with these two traits among a total of 24,341 women from the Nurses’ Health Study (NHS, N = 2,287) and the Women’s Genome Health Study (WGHS, N = 22,054). Linear regression was used to assess the marginal association of each SNP with each phenotype. We adjusted for multiple testing within each gene to identify statistically significant SNP associations at the gene level. To evaluate the overall evidence for an excess of statistically significant gene associations over the proportion expected by chance, we applied a one-sample test of proportion to each group of candidate genes. The steroid-hormone metabolism and biosynthesis pathway was found significantly associated with both age at menarche and age at natural menopause (P = 0.040 and 0.011, respectively). In addition, the group of genes associated with precocious or delayed puberty was found significantly associated with age at menarche (P = 0.013), and the group of genes involved in premature ovarian failure with age at menopause (P = 0.025).     

Migration,socio-economic status and age at menarche and age at menopause in the Yucatan,Mexico

The possible effects of migration and socio-economic status (SES) on age at menarche (MENA), age at menopause (MENO), potential reproductive period (PRP), and the correlation between MENA and MENO, were studied in 216 women in the Yucatan, Mexico. They were divided into three groups: migrant from the sisal-growing area on the coast, and sisal and coastal sedentary. Coastal sedentary women, living in the best socio-economic conditions, have the youngest MENA and the oldest MENO. Early migrant women have a significantly younger MENO (p.<0.05) and shorter PRP than Coastal sedentary women. There was no evidence of selective migration for MENA. When the Migrant, Sisal and Coastal sample were divided into cohorts by SES, it was impossible to obtain any clear picture. MENA increases with increased SES for the Coastal and Sisal cohorts, while the Migrant cohorts show an opposite trend. However, only the Low/Middle and High/Middle cohort differences for the Coastal sample are significant (p.<0.05, in both cases). It seems that migration has a limited affect on MENO and the PRP. Contrary to reports in the literature, the correlations between MENA and MENO and migrant status, and migrant socio-economic statuses, are negative, although these correlations were statistically significant in the Coastal sample.     

Finger patterns characteristics as determinants of total ridge count variability

The total ridge count (TRC) was viewed as a common composite trait with definite correlations between its components — the ridge counts (RC) of individual fingers. The TRC variability was accordingly examined as a function of the variability of these components. The distribution of pattern types on the fingers, the RC of patterns per total as well as per finger location, and the mean finger RC were all analyzed in relation to the RC variability and to a newly described phenomenon — the mutual influence on the RC variability of different patterns present concomitantly in an individual. It was concluded that the TRC variability is conditioned by the frequencies of the same genes which are responsible for the presence of the different finger pattern types. A high negative correlation coefficient, −0.901, was found between the pattern intensity index (PII) and the coefficient of variation of the TRC. The linear regression equation was: CV=90.75−4.20 PII. Biological isolation and the ensuing consanguinity may affect the TRC variability of a population by modifying the frequencies of these genes. This influence may be a decreasing as well as an increasing one. In contrast, when a common metric trait which is determined by additive genes without any dominance (as the TRC is frequently believed to be) is subjects to consanguinization effects, only a decrease in the variation is expected. The dermatoglyphics of 625 Jewish males were investigated and the general character of some dermatoglyphic regularities and trends was compared with and corroborated by data from the literature.     

Breeding like rabbits: global patterns of variability and determinants of European wild rabbit reproduction

The importance of European wild rabbits Oryctolagus cuniculus both as a pest in some areas and as a key prey species in others emphasizes the need to understand what controls its population dynamics worldwide. In this study we aim to describe the variability in rabbit breeding parameters and identify the main factors that govern it at a global scale. Despite the species' wide distribution, some reproductive traits such as short sexual maturity age, duration of gestation period, and existence of post-partum oestrus are similar in all populations conferring the species a high breeding potential. Nevertheless, other aspects vary substantially among regions resulting in highly different population productivities and also across years. These latter parameters are the length of breeding season, proportion of pregnant females, age of first reproduction, and number and size of litters. Our results show that variability in these attributes is mainly affected by a combination of environmental controls (i.e. temperature, resource availability, and photoperiod) and individual properties (age and body weight). On the other hand, the effect of other factors such as population density could not be demonstrated. Knowledge about the factors driving global reproduction patterns of European wild rabbits will improve our understanding about their population dynamics, and thus will help to optimize the management and conservation of their populations.     

Breast cancer susceptibility loci in association with age at menarche,age at natural menopause and the reproductive lifespan

Background: Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with breast cancer risk. Some of these loci have unknown functional significance and may mediate the effects of hormonal exposures on breast cancer risk. We examined relationships between breast cancer susceptibility variants and menstrual/reproductive factors using data from two population-based studies. Methods: The first analysis was based on a sample of 1328 women age 20–74 who participated as controls in a case–control study of breast cancer conducted in three U.S. states. We evaluated the associations between age at menarche, age at natural menopause and the reproductive lifespan with 13 previously identified breast cancer variants. Associations were also examined with a genetic score created as the sum of at-risk alleles across the 13 variants. For validation, significant results were evaluated in a second dataset comprised 1353 women age 43–86 recruited as part of a cohort study in Wisconsin. Results: Neither the genetic score nor any of the 13 variants considered individually were associated with age at menarche or reproductive lifespan. Two SNPs were associated with age at natural menopause; every increase in the minor allele (A) of rs17468277 (CASP8) was associated with a 1.12 year decrease in menopause age (p = 0.02). The minor allele (G) of rs10941679 (5p12) was associated with a 1.01 year increase in age at natural menopause (p = 0.01). The results were not replicated in the validation cohort (B = −0.61, p = 0.14 and B = −0.01, p = .0.98, respectively). Conclusions: The evaluated variants and reproductive experiences may work through separate pathways to influence breast cancer risk.     

Arterial pressure and its variability in conscious rabbits at different ages

Mean level and its variability of mean arterial pressure (MAP) were studied in 25 unanesthetized rabbits aged 6, 12, 18, 24 and 30 months. They were selected from the same large colony and bred with an ordinary rabbit food under a given environmental conditions. MAP in the aortic arch was continuously monitored with a catheter-transducer system for 3 hrs. Mean (M) and variance (V) of MAP for 3 hrs were not significantly altered with aging (p greater than 0.05, Kruskal-Wallis' multi-sample test). Intra-animal variations of the M and SD were small. Most of histograms of MAP for 3 hrs shows an exaggerated mode at any age. Distribution pattern of the histogram was not specific to age. These suggest that responsiveness of the baroreflex system should not be affected by aging from 6 to 30 months.     

Season of birth and recalled age at menarche.

All 8th-form schoolgirls from the municipality of Odense in Denmark were asked at what age they reached menarche, and 886 girls (97.6%) gave this information. There is no evidence for seasonality in the time of birth but for far more girls than expected menarche occurred during winter or summer and fewer than expected during spring and autumn. This pattern appears primarily in girls living in the suburbs and was not seen in those living in central Odense. The seasonality appears to be brought about by differences in mean age at menarche according to time of the year at birth.     

Father absence and age at menarche

Life history data, attractiveness ratings of male photographs, and attitudes towards partnership and child-rearing of 321 women were used to test four evolutionary models (quantitative reproductive strategy, male short-age, polygyny indication, and maternal reproductive interests) which attempt to explain the influence of family composition on reproductive strategies. Links between early menarche and other markers of reproductive strategy were investigated. Childhood stress and absence of a father figure, whether genetically related or not, were found to have accelerated menarche whereas having younger siblings decelerated it. Early menarche was associated with attractiveness ratings, the number of partners desired for the immediate future, and the early onset of intimate relationships. It was not linked with sociosexual orientation, mate choice criteria, and investment in the subjects’ own children, but these three markers were interrelated. The implications of the findings for the four evolutionary models are discussed.     

Seasonal characteristics of and age at menarche

Data from approximately 600 U.S. women were analyzed for seasonality in menarche. Data were converted to the ratio of observed (O) to expected (E) cases, based on an equal distribution of events over the year, per considered time span of the year. The greatest O/E ratio in menarche (1.55) occurred during January, followed by August (1.43) and July (1.24). The lowest O/E ratio in menarche occurred in February and May (0.68). Seasonal patterns in menarche were detected for the separate cohorts of women born during the 1940s, 1950s, and 1960s, with a shift from a December-January peak in menarche for those born in the 1940s and 1950s to an August-September peak for those born in the 1960s. Girls who were younger (8-14 yrs) at menarche exhibited a seasonal difference in the peak number of menarches by about 6 months in comparison to the pattern for girls who were older (15-17 yrs). Girls who experienced menarche during August-October were statistically significantly younger (p less than 0.05) than those born during the other three seasons. Season of birth was not statistically significantly associated with season of menarche. Overall, no 12-month pattern was substantiated by cosinor analysis in the month of menarche. However, a 6-month rhythm was detected in menarche for women born between 1940 and 1960 (p = 0.004, A = 29% M, phi = January and July).     

Age at menarche: the influence of environmental conditions

Age at menarche was studied by the recollection method in two groups of Causasian Jewish high school girls, inhabitants of two towns in Israel, Safad and Elat. The two towns differ mainly in climatic conditions. The age at menarche was found to be significantly lower (P<0.02) in the hot town of Elat than in the temperate town of Safad: 13.30±1.21 and 13.58±0.9 years, respectively (mean ±SD). A significant association was found between the age at menarche and the town in which the girls lived. Accordingly, in the hot town of Elat, the percentage of girls who had their first menstrual cycle by the age of 12 years and earlier, was more than double that of the girls in Safad (17.9% and 7.1%, respectively). It is concluded that the environmental temperature, with or without any possible interaction of humidity, is probably responsible for the tendency for an earlier onset of menarche in girls living in the hot town of Elat.     

Malaria prevention in north-eastern Tanzania: patterns of expenditure and determinants of demand at the household level

Background

In sub-Saharan Africa, preschool children represent the population most vulnerable to malaria and malnutrition. It is widely recognized that malnutrition compromises the immune function, resulting in higher risk of infection. However, very few studies have investigated the relationship between malaria, malnutrition and specific immunity. In the present study, the anti- Plasmodium falciparum IgG antibody (Ab) response was evaluated in children according to the type of malnutrition.

Methods

Anthropometric assessment and blood sample collection were carried out during a cross-sectional survey including rural Senegalese preschool children. This cross-sectional survey was conducted in July 2003 at the onset of the rainy season. Malnutrition was defined as stunting (height-for-age <-2 z-scores) or wasting (weight-for-height <-2 z-scores). The analysis was performed on all malnourished children in July (n = 161, either stunted, n = 142 or wasted, n = 19), pair-matched to well-nourished controls. The IgG Ab response to P. falciparum whole extracts (schizont antigens) was assessed by ELISA in sera of the included children.

Results

Both the prevalence of anti-malarial immune responders and specific IgG Ab levels were significantly lower in malnourished children than in controls. Depending on the type of malnutrition, wasted children and stunted children presented a lower specific IgG Ab response than their respective controls, but this difference was significant only in stunted children (P = 0.026). This down-regulation of the specific Ab response seemed to be explained by severely stunted children (HAZ ≤ -2.5) compared to their controls (P = 0.03), while no significant difference was observed in mildly stunted children (-2.5 < HAZ <-2.0). The influence of child malnutrition on the specific anti- P. falciparum Ab response appeared to be independent of the intensity of infection.

Conclusion

Child malnutrition, and particularly stunting, may down-regulate the anti- P. falciparum Ab response, both in terms of prevalence of immune responders and specific IgG Ab levels. This study provides further evidence for the influence of malnutrition on the specific anti-malarial immune response and points to the importance of taking into account child malnutrition in malaria epidemiological studies and vaccine trials.     

Rates of evolutionary change in viruses: patterns and determinants

Understanding the factors that determine the rate at which genomes generate and fix mutations provides important insights into key evolutionary mechanisms. We review our current knowledge of the rates of mutation and substitution, as well as their determinants, in RNA viruses, DNA viruses and retroviruses. We show that the high rate of nucleotide substitution in RNA viruses is matched by some DNA viruses, suggesting that evolutionary rates in viruses are explained by diverse aspects of viral biology, such as genomic architecture and replication speed, and not simply by polymerase fidelity.