Coital frequency and twinning

In a comparative study to enquire whether parents of twins, especially of dizygotic twins, have a higher frequency of sexual intercourse than parents of singleton infants, data on sociodemographic status, coital frequency and other variables were collected using a postal questionnaire. Parents of all twins born alive in Denmark in 1984 or 1985 were included as cases and a random sample of parents of singleton infants born in the same period were controls. No evidence of any difference in coital frequency was found between parents of twins (neither dizygotic twins nor monozygotic) and parents of singleton infants.     

An excess of the Pi Sallele in dizygotic twins and their mothers

Summary A significant excess of the ₁ (protease inhibitor) Pi ^S allele has been found in 147 pairs of dizygotic (DZ) twins, but frequencies in 170 pairs of monozygotic (MZ) twins do not differ from those in a sample of 1007 blood donors. In 51 mothers of DZ twins the frequency of the Pi ^S allele was double than in the same sample of donors, but there was no corresponding increase in the fathers of DZ twins nor in the parents of MZ twins. In an independent sample of 66 mothers of twins of unknown zygosity, there was also a significant excess of Pi ^M Pi^S and Pi^M Pi^Z phenotypes, and this was particularly marked in the subsample of mothers of opposite-sex twin pairs. We speculate that lowered protease inhibitor levels in women carrying the Pi ^S allele may enhance sperm migration, increase the probability of multiple ovulation, or both.     

Why zygosity of multiple births is not always obvious: an examination of zygosity testing requests from twins or their parents.

This paper examines why parents of twins or adult twins themselves request zygosity testing. Of 405 multiples including 8 sets of triplets, the majority (93%) were monozygotic. Age of testing ranged from 0 days to 73 years. About 50% of requests came from parents or twins who were curious about, or expressed a need to be certain of, their zygosity. Other reasons included health concerns (current or future), other twins in the family, and misinformation about zygosity, frequently because of the erroneous assumption that all dichorionic twins are dizygotic. Parents of monozygotic twins may expect their twins to be 'identical' and believe their twins to be dizygotic because of minor phenotypic differences between them. Dizygotic twins like other siblings may share a phenotypic resemblance. Health professionals should be aware that zygosity of multiples may not always be obvious to parents and that accurate knowledge of zygosity may be justified.     

Genetic and Environmental Influences on the Tracking of Body Size from Birth to Early Adulthood

Objective: This study identified genetic and environmental influences on the tracking of body size from birth to 16 to 18.5 years of age. Research Methods and Procedures: Longitudinal information was collected from a nationally representative sample of Finnish twin adolescents (birth cohorts 1975 to 1979) and their parents through questionnaires mailed when the twins were ages 16 and 18.5 years old. The sample included 702 monozygotic, 724 same‐sex dizygotic, and 762 opposite‐sex dizygotic sets of twins. The measures used were length, weight, ponderal index (kilograms per cubic meters), and gestational age at birth, and height, weight, and body mass index (kilograms per square meters) at 16 to 18.5 years of age. The changes in genetic and environmental influences on body size from birth to early adulthood were analyzed by quantitative genetic modeling. Results: The twins who had a higher weight or ponderal index at birth were taller and heavier in early adulthood, whereas those who were longer at birth were taller, but not heavier, later in life. Adult height was affected more by the birth size than body mass index. In the genetic modeling analyses, the genetic factors accounting for the variation of body size became more apparent with age, and both genetic and environmental influences on stature had a sizable carry‐over effect from birth to late adolescence, whereas for relative weight, the influences were more age‐specific. Discussion: The genetic and environmental architecture of body size changes from birth to adulthood. Even in monozygotic twins who share their genetic background, the initially larger twin tended to remain larger, demonstrating the long‐lasting effects of fetal environment on final body size.     

Association studies using family pools of outcrossing crops based on allele-frequency estimates from DNA sequencing

Key message

We propose a method in which GBS data can be conveniently analyzed without calling genotypes.

Abstract

F2 families are frequently used in breeding of outcrossing species, for instance to obtain trait measurements on plots. We propose to perform association studies by obtaining a matching “family genotype” from sequencing a pooled sample of the family, and to directly use allele frequencies computed from sequence read-counts for mapping. We show that, under additivity assumptions, there is a linear relationship between the family phenotype and family allele frequency, and that a regression of family phenotype on family allele frequency will estimate twice the allele substitution effect at a locus. However, medium-to-low sequencing depth causes underestimation of the true allele substitution effect. An expression for this underestimation is derived for the case that parents are diploid, such that F2 families have up to four dosages of every allele. Using simulation studies, estimation of the allele effect from F2-family pools was verified and it was shown that the underestimation of the allele effect is correctly described. The optimal design for an association study when sequencing budget would be fixed is obtained using large sample size and lower sequence depth, and using higher SNP density (resulting in higher LD with causative mutations) and lower sequencing depth. Therefore, association studies using genotyping by sequencing are optimal and use low sequencing depth per sample. The developed framework for association studies using allele frequencies from sequencing can be modified for other types of family pools and is also directly applicable for association studies in polyploids.     

Social class and human twinning

In a comparative study to examine the effect of social factors on human twinning, data on sociodemographic and other factors were collected from parents of all twins born alive in Denmark in 1984 or 1985 and from a random sample of parents of singleton infants born in the same years. A postal questionnaire was used. The twins were classified as monozygotic (MZ) or dizygotic (DZ) twins by the similarity method. A trend was found in DZ-twinning, with significantly fewer DZ-twins born in the lower social classes, but not in MZ-twinning. All results were controlled for maternal age and parity.     

Multiple birth and Down's disease]

The frequency of twinning among newborns with Down's syndrome (2,11+/-0,6%)was significantly higher than in the general populaltion (0,73+/-0,3%). The increase in the rate of multiple births of children with trisomy-21 occurred due to almost three-fold excess in the frequency of dizygotic (discordant) twin pairs over the expected level. The increase in the frequency of dizygotic twins with Down's syndrome was explained by the combined effect of two independent factors: the increase in probability of dizgotic twins natality and the enhanced rate of children birth with trisomy-21, which depended on the increase in mother's age.     

GENETIC ANALYSIS OF MORNINGNESS AND EVENINGNESS

We studied the influence of genetic factors on individual differences in morningness-eveningness in a sample of Dutch twin families. Data were collected from adolescent twins (mean age 17.8 yr) and their parents (mean age of fathers 48.0 yr and of mothers 46.0 yr) and a sample of older twins (mean age 46.5 yr). Scores on morningness-eveningness were rated on a 5-point scale. Parents were more morning oriented than their children, and women were more morning oriented than men. With a twin-family study, separation of genetic and environmental influences on variation in morningness-eveningness is possible. Including parents and older twins in the study makes it possible to explore generation differences in these effects. The correlation between monozygotic twins was more than twice the correlation between dizygotic twins. This indicates that genetic effects may not operate in an additive manner. Therefore, a model that included genetic dominance was explored. Biometrical model fitting showed no sex differences for the magnitude of genetic and environmental factors. The total heritability—the sum of additive and nonadditive genetic influences—for morningness-eveningness was 44% for the younger generation and 47% for the older generation. However, the genetic correlation between the generations turned out to be lower than 0.5, suggesting that different genes for morningness-eveningness are expressed in both generations. (Chronobiology International, 18(5), 809-822, 2001)     

GENETIC ANALYSIS OF MORNINGNESS AND EVENINGNESS

We studied the influence of genetic factors on individual differences in morningness-eveningness in a sample of Dutch twin families. Data were collected from adolescent twins (mean age 17.8 yr) and their parents (mean age of fathers 48.0 yr and of mothers 46.0 yr) and a sample of older twins (mean age 46.5 yr). Scores on morningness-eveningness were rated on a 5-point scale. Parents were more morning oriented than their children, and women were more morning oriented than men. With a twin-family study, separation of genetic and environmental influences on variation in morningness-eveningness is possible. Including parents and older twins in the study makes it possible to explore generation differences in these effects. The correlation between monozygotic twins was more than twice the correlation between dizygotic twins. This indicates that genetic effects may not operate in an additive manner. Therefore, a model that included genetic dominance was explored. Biometrical model fitting showed no sex differences for the magnitude of genetic and environmental factors. The total heritability—the sum of additive and nonadditive genetic influences—for morningness-eveningness was 44% for the younger generation and 47% for the older generation. However, the genetic correlation between the generations turned out to be lower than 0.5, suggesting that different genes for morningness-eveningness are expressed in both generations. (Chronobiology International, 18(5), 809–822, 2001)     

Menstrual characteristics of mothers of twins

The menarcheal age and frequency of menstrual disorders in mothers of dizygotic (DZ) and monozygotic (MZ) twins born in Denmark in 1984 or 1985 were compared with a control sample of mothers of singleton infants born in the same period. Compared to control mothers, mothers of DZ twins had a lower menarcheal age and a lower frequency of menstrual irregularities--menstrual cycles exceeding 5 weeks duration, varying length of menstrual cycles and episodes of menostasia. Mothers of MZ twins had a higher frequency of intermenstrual bleeding compared to mothers of singletons. All results were adjusted for maternal age and parity. The findings are relevant to the interpretation of aetiological factors leading to twin births and support the hypothesis of differences in sex hormone activity of the mothers of DZ twins in comparison with other women.     

Factors in the rejection and survival of captive cotton top tamarins (Saguinus oedipus)

Captive colonies of cotton top tamarins experience a high rate of rejection of infants within the 1st week of life. The rates of rejection and survival to maturity (2 or more years) among 659 live colony-born infants were correlated with rearing, birth group, litter size, season of birth, gender, origin of parents, experience of parents raising siblings, parity and age of parents, and experience of parent pairs. The most important factors associated with low rejection rates were family life and parental experience raising infants. Infants born into family groups or reared in families were rejected at a significantly lower rate. Rejection of infants whose sires were raised with siblings was significantly lower. Paternal experience was more important than maternal experience. Litter size had no effect on rejection of infants born to family groups, whereas, rejection of triplets was significantly higher than twins or singles among those born to parents alone. Rejection was significantly higher among primiparous births than multiparous birth. The combined experience of colony-born parents was not related to rejection if there were no sibling helpers in the cage at the time of birth. Rejection was significantly lower if sibling helpers were present. High survival of infants who were not rejected was correlated with rearing by or being born into family groups and higher parity and older age of the sires.     

The 5-HTTLPR Confers Susceptibility to Anorexia Nervosa in Han Chinese: Evidence from a Case-Control and Family-Based Study

Accumulating evidence has implied that serotonin system dysfunction may be involved in the etiology of anorexia nervosa (AN). Serotonin-transporter-linked promoter region (5-HTTLPR) polymorphism is the genetic variant coding for the serotonin transporter and has a modulatory effect on its expression. This study aimed to investigate the possible association between the 5-HTTLPR and the susceptibility and severity of AN in Han Chinese using a case-control (255 patients and 351 controls) and family based study (198 trios). Eating disorder examination was used to measure the severity of AN behavioral symptoms. For the case-control study, the 5-HTTLPR showed significant association with AN in our sample (genotypic P = 0.03). The frequency of S allele was significantly higher in patients than that in controls (OR = 1.38, 95%CI: 1.06–1.79, P = 0.017). For the family-based study, the S allele of 5-HTTLPR was preferentially transmitted rather than non-transmitted from the parents to affected offspring (P = 0.013). The results of ANCOVA test revealed no significant association between the 5-HTTLPR polymorphism and severity of AN. Our findings suggested that 5-HTTLPR is able to confer susceptibility to AN in Han Chinese.     

Genetic and environmental influences on Anxious/Depression during childhood: a study from the Netherlands Twin Register

For a large sample of twin pairs from the Netherlands Twins Register who were recruited at birth and followed through childhood, we obtained parental ratings of Anxious/Depression (A/D). Maternal ratings were obtained at ages 3 years (for 9025 twin pairs), 5 years (9222 pairs), 7 years (7331 pairs), 10 years (4430 pairs) and 12 years (2363 pairs). For 60-90% of the pairs, father ratings were also available. Multivariate genetic models were used to test for rater-independent and rater-specific assessments of A/D and to determine the genetic and environmental influences on individual differences in A/D at different ages. At all ages, monozygotic twins resembled each other more closely for A/D than dizygotic twins, implying genetic influences on variation in A/D. Opposite sex twin pairs resembled each other to same extent as same-sex dizygotic twins, suggesting that the same genes are expressed in boys and girls. Heritability estimates for rater-independent A/D were high in 3-year olds (76%) and decreased in size as children grew up [60% at age 5, 67% at age 7, 53% at age 10 (60% in boys) and 48% at age 12 years]. The decrease in genetic influences was accompanied by an increase in the influence of the shared family environment [absent at ages 3 and 7, 16% at age 5, 20% at age 10 (5% in boys) and 18% at age 12 years]. The agreement between parental A/D ratings was between 0.5 and 0.7, with somewhat higher correlations for the youngest group. Disagreement in ratings between the parents was not merely the result of unreliability or rater bias. Both the parents provided unique information from their own perspective on the behavior of their children. Significant influences of genetic and shared environmental factors were found for the unique parental views. At all ages, the contribution of shared environmental factors to variation in rater-specific views was higher for father ratings. Also, at all ages except age 12, the heritability estimates for the rater-specific phenotype were higher for mother ratings (59% at age 3 and decreasing to 27% at age 12 years) than for father ratings (between 14 and 29%). Differences between children, even as young as 3 years, in A/D are to a large extent due to genetic differences. As children grow up, the variation in A/D is due in equal parts to genetic and environmental influences. Anxious/Depression, unlike many other common childhood psychopathologies, is influenced by the shared family environment. These findings may provide support for why certain family therapeutic approaches are effective in the A/D spectrum of illnesses.     

What effect does classroom separation have on twins' behavior, progress at school, and reading abilities?

We investigated the effects of classroom separation on twins' behavior, progress at school, and reading abilities. This investigation was part of a longitudinal study of a nationally-representative sample of twins (the E-risk Study) who were assessed at the start of school (age 5) and followed up (age 7). We examined three groups of twins: pairs who were in the same class at both ages; pairs who were in separate classes at both ages; and pairs who were in the same class at age 5, but separated by age 7. When compared to those not separated, those separated early had significantly more teacher-rated internalizing problems and those separated later showed more internalizing problems and lower reading scores. Monozygotic (MZ) twins showed more problems as a result of separation than dizygotic (DZ) twins. No group differences emerged for externalizing problems, ADHD or prosocial behaviors. The implications of the findings for parents and teachers of twins, and for school practices about separating twins, are discussed.     

A deletion mutation in GDF9 in sisters with spontaneous DZ twins.

A loss of function mutation in growth differentiation factor 9 (GDF9) in sheep causes increased ovulation rate and infertility in a dosage-sensitive manner. Spontaneous dizygotic (DZ) twinning in the human is under genetic control and women with a history of DZ twinning have an increased incidence of multiple follicle growth and multiple ovulation. We sequenced the GDF9 coding region in DNA samples from 20 women with DZ twins and identified a four-base pair deletion in GDF9 in two sisters with twins from one family. We screened a further 429 families and did not find the loss of function mutation in any other families. We genotyped eight single nucleotide polymorphisms across the GDF9 locus in 379 families with two sisters who have both given birth to spontaneous DZ twins (1527 individuals) and 226 triad families with mothers of twins and their parents (723 individuals). Using case control analysis and the transmission disequilibrium test we found no evidence for association between common variants in GDF9 and twinning in the families. We conclude that rare mutations in GDF9 may influence twinning, but twinning frequency is not associated with common variation in GDF9.     

Zygosity misclassification of twins at birth in Japan.

Though twinning rates have been rapidly increasing in Japan, the problem of zygosity misclassification at birth has been paid little attention. By analyzing four independent samples, the authors found that at a constant rate about 25-30% of monozygotic twins were misclassified as dizygotic twins at birth. This percentage is in very good accordance with that of monozygotic twins having dizygous placenta. Generally the obstetricians informed twins' parents about their children's zygosity. The number of placentas, as informed by obstetricians, was very strongly associated with zygosity. Concluding, even now many monozygotic twins in Japan may be misclassified as dizygotic at birth by obstetricians based solely on the number of placenta.     

Individual differences in adolescent religiosity in Finland: familial effects are modified by sex and region of residence.

Data from 16-year-old Finnish twin pairs were used to estimate familial effects on religiosity and the modification of those effects by sex and residential region. The sample of 2265 twin boys and 2521 twin girls formed 779 monozygotic and 1614 dizygotic pairs, 785 of the same sex and 829 of opposite sex. We compared religiosity scores of twins living in more rural and traditional northern Finland with those living in the more urban and secular southern region. Girls had higher religiosity scores than did boys, and twins living in northern Finland had higher religiosity scores than those resident in southern Finland. Correlations for monozygotic twins were slightly higher than those for dizygotic twins, and covariance modeling found modest heritability of religiosity [11% (95% CI 0-24) for girls; 22% (95% CI 6-38) for boys], and substantial shared environmental effects [60% (95% CI 49-69) and 45% (95% CI 31-57)] among girls and boys, respectively. The correlation between shared environmental effects in boys and girls was estimated to be 0.84 (95% CI 0.73-0.99). In analyses distinguishing region of residence, girls living in southern Finland were found to have significantly higher unshared environmental effects than girls in northern Finland, while boys living in the urban south appeared to have lower shared environmental effects, and higher additive genetic effects, than boys living in the rural north.     

Correlations between relatives for acrocentric association frequency

Summary Acrocentric association was investigated in peripheral blood lymphocytes of twins (10 monozygotic and 11 dizygotic pairs), newborns and both parents (30 families), and spouses (51 pairs). Seventy two hour cultures were G-banded and scored for both absolute and relative acrocentric association frequency, except in the case of the spouse pairs where only the absolute frequency was measured. Both relative and absolute parameters of acrocentric association show positive correlations between relatives with the values being highest and most consistent in monozygotic twins, intermediate in parent and offspring, and most variable in dizygotic twins. Husband and wife pairs from our family collections show a positive correlation for the absolute parameter but not for relative parameters. The environmental factors responsible have not been identified.A rough estimate of broad sense heritability (0.81) has been made for the relative parameters. It probably contains a large component due to genetic dominance. Heritability of the absolute parameters is probably lower than for the relative parameters though estimation of its value is complicated by inconsistent results. A model is proposed to account for the variation in satellite association frequency which contains two elements: (i) The genotype determines the ratio of one chromosome type to another in the population of associated chromosomes. (ii) All other environmental factors influence the absolute frequency of association without altering this basic ratio.