A polygenic score for age-at-first-birth predicts disinhibition.

BACKGROUND: A recent genome-wide association study identified molecular-genetic associations with age-at-first-birth. However, the meaning of these genetic discoveries is unclear. Drawing on evidence linking early pregnancy with disinhibitory behavior, we tested the hypothesis that genetic discoveries for age-at-first-birth predict disinhibition. METHODS: We included participants with genotype data from the two-decade-long Environmental Risk (E-Risk) Study (N = 1,999) and the four-decade-long Dunedin Study (N = 918). We calculated a genome-wide polygenic score for age-at-first-birth and tested whether it was associated with a range of disinhibitory outcomes across the life course, including low childhood self-control; risk for externalizing psychopathology; officially recorded criminal offending; substance dependence; informant reports of disinhibitory problems; and number of lifetime sexual partners. We further tested whether associations were attributable to accelerated pubertal maturation. RESULTS: In both cohorts, the age-at-first-birth polygenic score predicted low childhood self-control, externalizing psychopathology, officially recorded criminal offending, substance dependence, and number of sexual partners. Associations were modest, but robust across replication. Childhood disinhibition partly mediated associations between the polygenic score and reproductive behaviors. In contrast, associations were not attributable to accelerated pubertal timing. CONCLUSIONS: Genomic discoveries for age-at-first-birth are about more than reproductive biology: They provide insight into the disinhibitory traits and behaviors that accompany early parenthood. Age-at-first-birth is a useful proxy phenotype for researchers interested in disinhibition. Further, interventions that improve self-regulation abilities may benefit young parents and their children.

Double aneuploidy (48,XXY,+21) of maternal origin in a child born to a 13-year-old mother: evaluation of the maternal folate metabolism.

The occurrence of non-mosaic double trisomy is exceptional in newborns. In this paper, a 48,XXY,+21 child, the parental origin of the extra chromosomes and the evaluation of the maternal folate metabolism are presented. The infant was born to a 13-year-old mother and presented with the typical clinical features of Down syndrome (DS). The origin of the additional chromosomes was maternal and most likely resulted from errors during the first meiotic division. Molecular analysis of 12 genetic polymorphisms involved in the folate metabolism revealed that the mother is heterozygous for the MTHFR C677T and TC2 A67G polymorphisms, and homozygous for the mutant MTRR A66G polymorphism. The maternal homocysteine concentration was 4.7 miromol/L, a value close to the one considered as a risk factor for DS in our previous study. Plasma methylmalonic acid and serum folate concentrations were 0.17 micromol/L and 18.4 ng/mL, respectively. It is possible that the presence of allelic variants for the folate metabolism and Hey concentration might have favored errors in chromosomal disjunction during gametogenesis in this young mother. To our knowledge, this is the first patient with non-mosaic Down-Klinefelter born to a teenage mother, resulting from a rare fertilization event combining an abnormal 25,XX,+21 oocyte and a 23,Y spermatozoon.

Genetics and the geography of health, behaviour and attainment.

Young people's life chances can be predicted by characteristics of their neighbourhood1. Children growing up in disadvantaged neighbourhoods exhibit worse physical and mental health and suffer poorer educational and economic outcomes than children growing up in advantaged neighbourhoods. Increasing recognition that aspects of social inequalities tend, in fact, to be geographical inequalities2-5 is stimulating research and focusing policy interest on the role of place in shaping health, behaviour and social outcomes. Where neighbourhood effects are causal, neighbourhood-level interventions can be effective. Where neighbourhood effects reflect selection of families with different characteristics into different neighbourhoods, interventions should instead target families or individuals directly. To test how selection may affect different neighbourhood-linked problems, we linked neighbourhood data with genetic, health and social outcome data for >7,000 European-descent UK and US young people in the E-Risk and Add Health studies. We tested selection/concentration of genetic risks for obesity, schizophrenia, teen pregnancy and poor educational outcomes in high-risk neighbourhoods, including genetic analysis of neighbourhood mobility. Findings argue against genetic selection/concentration as an explanation for neighbourhood gradients in obesity and mental health problems. By contrast, modest genetic selection/concentration was evident for teen pregnancy and poor educational outcomes, suggesting that neighbourhood effects for these outcomes should be interpreted with care.

Age at first sexual intercourse and teenage pregnancy in Australian female twins.

Girls who report first sexual intercourse during their early teen years have much higher rates of teenage pregnancy and childbearing than girls who delay sexual onset until older adolescence. In this study, we examine genetic and environmental influences on variation in teenage pregnancy and covariation with age at first sexual intercourse in two cohorts of Australian female twins. In the older twin cohort, born 1893-1964, we observe substantial heritable variation in teenage pregnancy that is largely shared with heritable variation in age at first sexual intercourse, with shared environment contributing little to variation in teenage pregnancy. Genetic influences on teenage pregnancy are smaller and nonsignificant in the younger twin cohort, born 1964-1971, where shared environment contributes much more and overlaps entirely with shared environmental variation in age at first intercourse.

Like mother, like daughter: a general practice study of maternal influences on teenage pregnancy.

This study confirmed the hypothesis that pregnant teenagers in the 1990s are more likely to have a mother who had a teenage pregnancy than non-pregnant teenagers. It also found that the daughters of teenage mothers are more likely to continue their own pregnancies.

PIP: General practice records were studied to identify differences between pregnant and nonpregnant teenagers in relation to their mothers' experiences. 37 females aged 13-19 years registered with the Honiton Group Practice who had had at least one pregnancy by January 1, 1996, were studied in detail. An equal number of nonpregnant controls also participated in the study. For 31 of the 37 girls in the study group and 34 of the 37 in the control group it was possible to establish whether their mother had had a teenage pregnancy. Half of the pregnant teenagers had a mother who had also had a teenage conception compared with 25% of the girls in the control group. These findings therefore confirm the hypothesis that pregnant teenagers in the 1990s are more likely to have a mother who had a teenage pregnancy than nonpregnant teens. The study also found that the daughters of teenage mothers are more likely to continue their own pregnancies.

Some aspects of obstetrics in black teenage pregnancy: a comparative analysis.

This article is based on an investigation into some aspects of obstetrics in black teenage pregnancy conducted by the authors at two hospitals in Port Elizabeth during the latter part of 1992. In that research, it was hypothesized that significant differences with regard to several obstetrical factors would be found between the teenagers and older controls. Three groups of primigravidae who had single births were compared and the data statistically analysed. There were 47 teenagers aged 13 to 16 years, 128 aged 17 to 19 years and 125 older females aged 20 to 30 years. A significantly higher incidence of anaemia and low birth mass neonates among the teenagers than among the controls was found. A significant association was also found between low antenatal clinic attendance (four or fewer visits) and low birth mass infants. No significant differences were found in regard to other obstetric variables, including incidence of sexually transmitted diseases and syphilis in particular.

PIP: In South Africa, two sociologists conducted a comparative study to examine obstetric aspects of 200 Black primigravidae who delivered at two Port Elizabeth hospitals in late 1992. The three groups included 47 women aged 13-16, 128 women aged 17-19, and 125 women aged 20-30. 22.3% of all women currently had a sexually transmitted disease (STD), especially syphilis (80% of those with an STD). 96.3% of all women had received prenatal care. Yet most received it in the third trimester. The two teenage groups were significantly more likely to have anemia (10 g/dl hemoglobin) than the 20-30 year old group (8.1% vs. 0.9%; p 0.05). They also were more likely to have low-birth-weight (LBW) infants (26.6-27.6% vs. 15.2%; p 0.05). Even though they also had a higher proportion of small for gestational age infants than the 20-30 year old group, the difference was not significant. Poor prenatal clinic attendance (1-4 visits) was significantly associated with LBW, often associated with premature labor (p 0.05). There were no significant differences between the groups for other obstetric variables. These findings show that Black pregnant teenagers in Port Elizabeth are at increased risk of anemia, of delivering an LBW infant, and of premature labor.

Pesquisa de los riesgos preconcepcional y prenatal / Screening of the pre-conception and prenatal risks

La evaluación del riesgo reproductivo a nivel comunitario incluye el diagnóstico de las condiciones que significan un peligro potencial para el desarrollo saludable de la gestación y el niño. En el presente trabajo se muestran los resultados de la pesquisa de los riesgos preconcepcional y prenatal en mujeres en edad fértil y gestantes, respectivamente, residentes en la provincia de Las Tunas. Se revisaron los registros y reportes estadísticos del Centro Provincial de Genética Médica correspondientes a los años 2007 y 2008 para tomar el universo de mujeres a evaluar y las estudiadas, con lo que se calculó la cobertura de ambos programas. Se determinaron las frecuencias relacionadas con los riesgos por cada condición de riesgo: cromosomopatías, hemoglobinopatías, malformaciones congénitas, teratogenicidad y otras afecciones hereditarias. El 55,0 por ciento de las mujeres evaluadas durante el último año y el 79,3 por ciento en el 2007 fue clasificada con algún riesgo preconcepcional, con un predominio de las cromosomopatías como criterio más frecuente de riesgo. El 40,7 por ciento de las 5 746 gestantes atendidas en el 2008 fue considerada con riesgos prenatales, por debajo del 49,2 por ciento en el año precedente. El riesgo por cromosomopatía fue el predominante en la evaluación prenatal, presente en 62,1 por ciento y 71,3 por ciento de las gestantes en el 2007 y el 2008, respectivamente, a expensas del embarazo en la adolescencia. Se requiere de criterios uniformes para la evaluación del riesgo genético en las mujeres, a las que se les ofrece un seguimiento especializado por los servicios comunitarios de Genética e interconsultas con otras especialidades

The assessment of reproductive risk at community level includes the diagnosis of conditions that are a potential risk for the healthy development of pregnancy and the baby. In the present paper the results of a screening of the pre-conception and prenatal risks in women of fertile age and pregnants, respectively, resident of the Las Tunas provinceare shown. The authors analyzed the registries and statistical reports from the Provincial Central of Medical Genetic corresponding to years 2007 and 2008 in order to include both the universe of women assessed and studied, estimating the coverage of both programs. The frequencies related to each risk condition, e.g. chromosomal diseases, hemoglobinopathies, birth defects, theratogenicity and other hereditary affections were al determined. 55.0 percent of women assessed during the last year and 79.3 percent in 2007 were classified with some pre-conception risk with a predominance of chromosomal diseases as the most frequent criterion of risk. The 40,7 percent of the 5 746 pregnants seen in 2008 was considered in prenatal risks, a figure under the 49,2 percent in the previous year. The risk of chromosomal disease was predominant in the prenatal assessment, present in the 62,1 percent and the 71,3 percent of pregnants in 2007 and 2008, respectively, at the expense of the pregnant during adolescence. It is necessary the presence of uniform criteria to assess the genetic risk in women who receive a specialized follow-up by Genetics community services and inter-consultation with other specialties

Pesquisa de los riesgos preconcepcional y prenatal / Screening of the pre-conception and prenatal risks

La evaluación del riesgo reproductivo a nivel comunitario incluye el diagnóstico de las condiciones que significan un peligro potencial para el desarrollo saludable de la gestación y el niño. En el presente trabajo se muestran los resultados de la pesquisa de los riesgos preconcepcional y prenatal en mujeres en edad fértil y gestantes, respectivamente, residentes en la provincia de Las Tunas. Se revisaron los registros y reportes estadísticos del Centro Provincial de Genética Médica correspondientes a los años 2007 y 2008 para tomar el universo de mujeres a evaluar y las estudiadas, con lo que se calculó la cobertura de ambos programas. Se determinaron las frecuencias relacionadas con los riesgos por cada condición de riesgo: cromosomopatías, hemoglobinopatías, malformaciones congénitas, teratogenicidad y otras afecciones hereditarias. El 55,0 por ciento de las mujeres evaluadas durante el último año y el 79,3 por ciento en el 2007 fue clasificada con algún riesgo preconcepcional, con un predominio de las cromosomopatías como criterio más frecuente de riesgo. El 40,7 por ciento de las 5 746 gestantes atendidas en el 2008 fue considerada con riesgos prenatales, por debajo del 49,2 por ciento en el año precedente. El riesgo por cromosomopatía fue el predominante en la evaluación prenatal, presente en 62,1 por ciento y 71,3 por ciento de las gestantes en el 2007 y el 2008, respectivamente, a expensas del embarazo en la adolescencia. Se requiere de criterios uniformes para la evaluación del riesgo genético en las mujeres, a las que se les ofrece un seguimiento especializado por los servicios comunitarios de Genética e interconsultas con otras especialidades (AU)

The assessment of reproductive risk at community level includes the diagnosis of conditions that are a potential risk for the healthy development of pregnancy and the baby. In the present paper the results of a screening of the pre-conception and prenatal risks in women of fertile age and pregnants, respectively, resident of the Las Tunas provinceare shown. The authors analyzed the registries and statistical reports from the Provincial Central of Medical Genetic corresponding to years 2007 and 2008 in order to include both the universe of women assessed and studied, estimating the coverage of both programs. The frequencies related to each risk condition, e.g. chromosomal diseases, hemoglobinopathies, birth defects, theratogenicity and other hereditary affections were al determined. 55.0 percent of women assessed during the last year and 79.3 percent in 2007 were classified with some pre-conception risk with a predominance of chromosomal diseases as the most frequent criterion of risk. The 40,7 percent of the 5 746 pregnants seen in 2008 was considered in prenatal risks, a figure under the 49,2 percent in the previous year. The risk of chromosomal disease was predominant in the prenatal assessment, present in the 62,1 percent and the 71,3 percent of pregnants in 2007 and 2008, respectively, at the expense of the pregnant during adolescence. It is necessary the presence of uniform criteria to assess the genetic risk in women who receive a specialized follow-up by Genetics community services and inter-consultation with other specialties (AU)

DNA analysis of abortion material assisted by histology screening.

In cases of rape leading to fertilization, paternity testing can retrospectively identify the assailant. Abortion material commonly represents a mixture of maternal and fetal tissue and blood, which cannot be differentiated with the naked eye. Consequently, DNA typing of abortion material may be complicated, including band overlap if maternal tissue predominates. Therefore, histology screening of the abortion content for typical fetal tissue components, such as chorionic villi, followed by selected DNA typing of this sample is suggested. This combined approach is illustrated by a selected case demonstrating the reliability and concurrence of the histology and genetic results.