Multiple regression analysis of twin data obtained from selected samples

The multiple regression analysis of twin data in which a cotwin's score is predicted from that of a proband (the member of a twin pair selected because of a deviant score) and the coefficient of relationship provides a powerful test of genetic etiology (DeFries and Fulker: Behav Genet 15:467-473, 1985). Moreover, when an augmented model containing an interaction term is fitted to the same data set, direct estimates of heritability (h2) and the proportion of variance owing to shared environmental influences (c2) are also obtained. In the present paper, the expected partial regression coefficients estimated from these models are derived, and the flexibility of the general approach is illustrated. An extended model is formulated for the analysis of data from combined samples of affected and control twin pairs that yields tests for differential h2 and c2 in the two groups as well as pooled estimates of these parameters. The application of these models is illustrated by an analysis of data from reading-disabled and control twin pairs. Because of the ease, flexibility, and utility of the multiple regression analysis of twin data, it is an appealing alternative to more traditional model-fitting approaches.     

Freiberg’s Infraction in Identical Twins: A Case Report

Freiberg's infraction is an ostechondrosis of a lesser metatarsal head resulting in degeneration of the metatarsophalangeal joint. Several mechanisms have been suggested in its pathenogenesis. Freiberg first described the entity and believed single impact trauma was the underlying cause. Repetitive biomechanical microtrauma is the most widely accepted etiologic theory. Other factors contributing to its development include aseptic necrosis, ischemia, and a congenital predisposition. We present a case report of Freiberg's infraction occurring in identical twins involving multiple metatarsals in various stages of degeneration. One of the twins was affected unilaterally whereas the other twin was affected bilaterally. Both twins had involvement of the second metatarsal on the same side extremity. The occurrence of Freiberg's infraction in identical twins suggests that an underlying congenital predisposition to the condition may play more of a role than previously considered.     

Genetics: Genetic analysis prior to selective fetal reduction in multiple pregnancy: technical aspects and clinical outcome

Multiple pregnancies resulting from ovarian stimulation areat a higher risk of carrying at least one fetus affected byMendelian or chromosomal anomalies, the incidence of which isdirectly related to the order of multiples. Genetic analysisbefore fetal reduction was offered to both high-and low-riskpregnant women carrying two or more fetuses after ovulationinduction. Chorionic villus sampling (CVS) and fetal reductionwere achieved by transabdominal needling. The use of short-termculture, the polymerase chain reaction and fresh tissue enzymaticanalyses have made it possible for genetic diagnosis to be availablein a few days. A total of 100 patients had multifetal pregnancyreduction performed by a single operator; all of them completedpregnancy and none was lost at follow-up. The total fetal lossbefore 24 weeks was 7% and no statistically significant relationshipwas found with the final number of fetuses and CVS. Perinatallosses (3.9%) were only present in the series with a final numberof two fetuses. Pregnancy duration and birthweight were significantlyhigher in singletons than in twins, but were not related toCVS. The rate of chromosomal disorders was higher (7.2%) inthe study series than in singleton pregnancies not undergoingfetal reduction. Diagnostic error due to incorrect samplingwas reported in 1.5% of cases. These data support fetal reductionas a valuable strategy to improve the outcome of multiple pregnancy.The outcome of pregnancies reduced to singletons was significantlybetter than of those reduced to twins, and was not related toCVS. Therefore, prenatal genetic diagnosis should become anintegral part of counselling on multiple pregnancy, and is stronglyrecommended when reduction to singleton pregnancy is requested.     

Twin study of genetic and environmental effects on lipid levels

A study of 106 pairs of monozygotic (MZ) and 94 pairs of dizygotic (DZ) twins tested the hypothesis that part of the previously described genetic influence on blood lipid levels can be ascribed to closer similarities among MZ than among DZ twin pairs in environmental factors that affect lipid levels. Participants were adult twin volunteers (age 17-66; 64 male and 136 female pairs) who were selected from the NH & MRC Twin Registry or were respondents to advertisements. They completed a 4-day weighed food diary from which mean nutrient intake was derived. Information on lifestyle and demographic variables was obtained by questionnaire and a nonfasting blood sample was taken for measures of total, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol and the HDL2 and HDL3 subfractions. Height and weight were measured, and body mass index (BMI) was calculated (kg/m2). Estimates of the heritability of sex-adjusted lipid levels were 0.72 for total cholesterol, 0.79 for HDL cholesterol, 0.69 for HDL2, 0.20 for HDL3, 1.06 for LDL cholesterol, and 0.44 for sex-adjusted BMI. In all cases except for HDL3, genetic variance was statistically significant. After adjusting for the effects of environmental variables in three different ways, the estimates of heritability were somewhat lower for total cholesterol, HDL2, and BMI, and those for HDL cholesterol (borderline) and LDL cholesterol (definitely) remained statistically significant but were decreased. A genetic influence on HDL3 was not found. Adjusted heritability estimates obtained from one method of analysis were 0.35 for total cholesterol, 0.49 for HDL, 0.04 for HDL2, -0.34 for HDL3, 0.66 for LDL, and 0.32 for BMI. These results suggest that the assumptions made in the classical twin study approach are not appropriate when examining genetic effects on lipid levels or BMI, or indeed on any biological variable that may be affected by environmental factors that tend to be more similar in MZ twins than in DZ twins. In these circumstances, more complex models may be needed to differentiate between genetic and environmental influences.     

82例双胎妊娠及其围产儿分析

自１９８８年１月～１９９３年１２月我院共分娩１０１２４例，双胎８２例。结果表明：双胎组早产，妊高征、贫血、胎膜早破、产后出血和围产儿死亡率明显高于单胎组，为此提出：①有双胎家族史、由药物诱导排卵的孕妇、孕吐严重、先兆流产和子宫大于停经月份者应作Ｂ超检查，有助于双胎的早期诊断。②妊娠３２周以后，双胎孕妇应连续卧床休息，注意营养，治疗合并症，对减少早产、增加新生儿体重和降低围产儿死亡率有重要意义。     

A genetic and environmental time series analysis of blood pressure in male twins

Systolic and diastolic blood pressures were measured on 254 monozygotic (MZ) and 260 dizygotic (DZ) male twin pairs, during middle age (average age 48 years) and at two later age points. Genetic and environmental components of covariation were modeled by time series. For both measures, shared environmental influences were absent and specific environmental influences were largely time-specific. Although heritability was about 0.5 at each time point, genetic variation present at middle age contributed only about 60% to that present 9 years later, the remaining 40% being new. Fifteen years later, at the third time point, no new genetic variation was evident, variation in individual differences being entirely attributable to genetic differences laid down at the two earlier ages. © 1993 Wiley-Liss, Inc.     

Body fat in identical twins reared apart: Roles for genes and environment

We report analyses of data on body fat from a cohort of 34 separated monozygotic twin pairs (MZA) and a matched sample of 38 pairs of monozygotic twins reared together (MZT) originally studied by James Shields. The correlation for MZA pairs was. 61 and the correlation for MZT pairs was. 75. These correlations did not differ significantly, nor did correlations differ between MZA pairs subclassified as having been raised in relatively more or less similar environments. Our results suggest important roles for both genes and environment in the accumulation of body fat and support other adoption studies in suggesting that adult environments rather than rearing environments are the most important nongenetic determinants of levels of body fat in adults.Supported by National Institute of Mental Health Grant MH43409 to R.A.P. and a Grant in Aid from the Dight Institute of Human Genetics to I.I.G.     

Sex-specific effects for body mass index in the new Norwegian twin panel

Sex-specific effects for body mass index (BMI) were explored in a newly established, population-based Norwegian twin panel. The sample includes 5,864 individuals, aged 18–25 years, who responded to a questionnaire containing items for zygosity classification, height, weight, health, health-related behaviors, well-being, and demographic information. Among the 2,570 intact pairs who returned the questionnaire there were 416 identical (MZ) male pairs, 387 fraternal (DZ) male pairs, 528 MZ female pairs, 443 DZ female pairs, and 796 unlike-sexed pairs. Alternate sets of models testing for either sex-specific genetic or environmental parameters were evaluated using structural equation analysis. Results from the most parsimonious model indicated that the genes contributing to variation in BMI are not identical for men and women; rather, some genetic effects were shared by the sexes and some were unique to each sex. Total variation in BMI could be explained by sex-specific additive genetic effects, as well as genetic and non-shared environmental effects common to men and women. Estimates of heritability were .708 for men and .789 for women, and the male-female genetic correlation was 0.622. The series of models specifying sex-specific shared environment also fit the data and suggests that shared environmental factors may be important for males but not for females. The findings raise questions concerning the relationship between sex-specific effects for BMI and sex differences in health outcomes. ©1995 Wiley-Liss, Inc.