Additional Sibling Research Articles

Old family secrets exposed

An elderly man and woman died after being burned in an automobile accident. DNA typing strongly confirmed that they were brother and sister. But further typing, on four additional presumed siblings, revealed some surprising and instructive genetic patterns. The additional information contradicts the original conclusion, and also reveals remarkably precise insights into events many years ago.

Effects of kinship on growth and movements of brown trout in field enclosures

Abstract – The effect of kinship on growth and use of space by individually PIT‐tagged 1+ brown trout was studied for 11 weeks in eight stream enclosures. Each enclosure consisted of two sections, separated by a region containing PIT‐detecting antennae, which enabled us to measure use of sections by all individuals. Two types of sibling groups were tested, a single sibling group, F1, consisting of four individuals that were reared together in hatchery tank ‘a’ (F1a) plus four additional siblings of the same family but raised in hatchery tank ‘b’ (F1b), and a mixed sibling group, consisting of four F1a individuals plus four siblings from a second family, F2. Based on kin theory and earlier laboratory studies, we expected that growth of the F1a individuals in the single sibling group to be greater than that of F1a individuals in the mixed family sibling group, but instead we found just the opposite. The variance of growth did not differ between treatments. Nor was there a difference in time F1a individuals spent together when they were in mixed versus single sibling groups. We did find that F1a individuals changed habitat more frequently than F2 individuals in the mixed sibling group but less frequently than F1b in the single sibling groups. Thus, our predictions based on kin theory for growth and behavior of brown trout were not supported by our data, and we suggest that the role of kin recognition for the ecology of salmonids deserves further attention.

Epithelial ovarian carcinoma and fertility of parents.

We studied the fertility of the parents of 163 women with epithelial ovarian carcinoma in two hospitals in New York City, compared with the parents of 159 controls from similar neighborhoods. We used unconditional logistic regression to control for covariates, including parity, oral contraceptive use, age at menarche, and Jewish ancestry. Compared with women with zero or one sibling, those with two, three or four or more siblings had adjusted odds ratios (95% confidence intervals) of 0.91 (0.47-1.77), 0.61 (0.28-1.37), and 0.50 (0.26-0.98). On average, each additional sibling was associated with a risk reduction to 0.80 (0.66-0.98). These findings support the hypothesis that heritable conditions associated with reduced fertility of the subjects' parents may contribute to risk and may explain some of the effects of parity on the risk of this carcinoma. Alternatively, they may reflect some unidentified aspect of the environment experienced by girls growing up in small families. If confirmed in other data sets, these findings imply that sibship size might have confounded previous estimates of risk associated with a family history of cancer or with Jewish ethnicity.

Persistent polyclonal B-cell lymphocytosis: further evidence for a genetic disorder associated with B-cell abnormalities.

Persistent polyclonal B-cell lymphocytosis (PPBL) is an intriguing disorder diagnosed predominantly in women, usually cigarette smokers, characterized by an increase in the number of polyclonal B lymphocytes. Abnormality of the B-cell population is also evidenced by the presence of multiple bcl-2/Ig gene rearrangements and the finding of an additional long arm chromosome 3q+ (i3)(q10) within a significant proportion of B cells. The physiopathology of PPBL is unknown but its association with the HLA DR7 phenotype suggests a possible genetic disorder. To further determine whether PPBL has a genetic predisposition, we have undertaken an extensive study in a large family of a patient diagnosed with PPBL. Three individuals among the first-degree relatives presented all the criteria for a diagnosis of PPBL. A slight increase in serum IgM without evidence of B-cell proliferation was shown in two additional siblings. Multiple bcl-2/Ig gene rearrangements, a typical feature of PPBL, were identified in 8/10 individuals among first-degree relatives. A statistically significant association was found between the presence of these rearrangements and of a paternal HLA haplotype. We conclude that PPBL has a familial occurrence suggesting an underlying genetic defect. The development of the complete syndrome probably relies on unidentified additional co-factors.

Beyond our pages

Beyond our pages

Netherlands twin family study of anxious depression (NETSAD).

In a longitudinal study of Dutch adolescent and young adult twins, their parents and their siblings, questionnaire data were collected on depression, anxiety and correlated personality traits, such as neuroticism. Data were collected by mailed surveys in 1991, 1993, 1995 and 1997. A total of 13,717 individuals from 3344 families were included in the study. To localise quantitative trait loci (QTLs) involved in anxiety and depression, the survey data were used to select the most informative families for a genome-wide search. For each individual a genetic factor score was computed, based on a genetic multivariate analysis of anxiety, depression, neuroticism and somatic anxiety. A family was selected if at least two siblings (or DZ twins) had extreme factor scores. Both discordant (high-low) and concordant (high-high and low-low) pairs were included in the selected sample. Once an extreme sibling pair was selected, all family members (parents and additional siblings of the selected pair) who had at least once returned a questionnaire booklet were asked to provide a DNA sample. In total, 2724 individuals from 563 families (1007 parents and 1717 offspring) were approached and 1975 individuals from 479 families (643 patients and 1332 offspring) complied by returning a buccal swab for DNA isolation. All offspring from selected families were asked to participate in a psychiatric interview and in a 24-hour ambulatory assessment of cardiovascular parameters and cortisol. The interview consisted of the WHO-Composite International Diagnostic Interview and was administered to 1253 offspring. In this paper we describe the genetic-epidemiological analyses of the survey data on anxiety, somatic anxiety, neuroticism and depression. We detail how these data were used to select families for the QTL study and discuss strategies that may help elucidate the molecular pathways leading from genes to anxious depression.

Patterns of genetic differentiation in resting egg banks of a rotifer species complex in Spain

Here we present the first population study on the genetic diversity of a rotifer species complex (Brachionus plicatilis) in a geographic area (Eastern Spain), which includes inland and coastal habitats. A novel approach was used by hatching resting eggs from sediment samples rather than sampling rotifers from the water column. Hatchlings from resting eggs sampled at 22 sites resulted in 434 clones which were screened using four polymorphic allozyme loci. A high level of genetic diversity was found consisting of 43 multilocus genotypes which were clustered into six well differentiated groups, often found in sympatry, with few or no hybrids between them. Mating experiments revealed preferences that supported the observed pattern of genetic differentiation. Some groups had restricted geographical distributions, and showed a preference for habitat type. Our results confirm patterns found in other zooplanktonic organisms and suggest that classical taxonomy has underestimated biological diversity in rotifers. The presence of additional cryptic sibling species in this complex seems very probable. Our study demonstrates the feasibility of using sediment sampling to explore genetic differentiation between species and populations, and shows the role of the resting egg bank in maintaining genetic diversity.

A Minimalist Approach to Gene Mapping: Locating the Gene for Acheiropodia, by Homozygosity Analysis

Acheiropodia is an autosomal recessive disease that results in hemimelia (lack of formation of the distal extremities). We performed a complete genome screen of seven members of an extended pedigree that included three siblings with acheiropodia. Homozygosity mapping was used to identify regions most likely to harbor the gene for acheiropodia in this pedigree. In these two key regions (14p and 7q), further genotyping of one additional affected member of this pedigree plus seven additional unaffected siblings provided evidence, through linkage analysis, that the 7q36 region contains the acheiropodia gene. In this region, a maximum two-point LOD score of 3.81 (4.2 with multipoint analysis) was achieved, and a homozygous haplotype spanning a region of 11.7 cM was seen in all affected in this pedigree. Finally, genotypic analysis of two additional cases of acheiropodia with no known relation to the other samples revealed homozygous sharing of a portion of the same haplotype on 7q36, which reduces the chromosomal location of the acheiropodia gene to an 8.6-cM region. Localization of this gene, at the screening level, by use of data from only three affected subjects, provides an example of how certain genes may be mapped by use of a minimal number of affected cases.

A note on the statistical power in extended twin designs.

The power to detect sources of genetic and environmental variance varies with sample size, study design, effect size and the statistical significance level chosen. We explored whether the power of the classical twin study may be increased by adding non-twin siblings to the classical twin design. Sample sizes to detect genetic and shared environmental variation were compared for kinships with only twins, kinships consisting of twins and one additional sibling, and kinships with twins and two additional siblings. The effect of adding siblings to the classical twin design was considered for univariate and bivariate analyses. For the univariate case, adding one non-twin sibling resulted in a decrease in sample size needed to detect additive genetic influences in the presence of environmental influences. However, adding two additional siblings did not decrease the number of subjects as compared to the classical twin design. The sample size required to detect common environmental factors was also greatly decreased by adding one non-twin sibling. Adding two non-twin siblings resulted in a small additional decrease. In models including additive genetic, dominant genetic, and unique environmental effects, adding one sibling to a twin family decreased the required sample size to detect dominant genetic influences. Adding two siblings to a twin family resulted in only a slight additional decrease in sample size. In the bivariate case a similar pattern of results was found, in addition to the observation that the overall required sample size, as expected, was lower than in the univariate case. The decrease in sample size from bivariate testing was more pronounced in a design with one or two additional siblings, as compared to a design with twins only. It is concluded that a well considered choice of family design, i.e. including families with twins and one or two additional siblings increases the statistical power to detect sources of variance due to additive and non-additive genetic influences, and common environment.

Multivariate genetic analysis of brain structure in an extended twin design.

The hunt for genes influencing behavior may be aided by the study of intermediate phenotypes for several reasons. First, intermediate phenotypes may be influenced by only a few genes, which facilitates their detection. Second, many intermediate phenotypes can be measured on a continuous quantitative scale and thus can be assessed in affected and unaffected individuals. Continuous measures increase the statistical power to detect genetic effects (Neale et al., 1994), and allow studies to be designed to collect data from informative subjects such as extreme concordant or discordant pairs. Intermediate phenotypes for discrete traits, such as psychiatric disorders, can be neurotransmitter levels, brain function, or structure. In this paper we conduct a multivariate analysis of data from 111 twin pairs and 34 additional siblings on cerebellar volume, intracranial space, and body height. The analysis is carried out on the raw data and specifies a model for the mean and the covariance structure. Results suggest that cerebellar volume and intracranial space vary with age and sex. Brain volumes tend to decrease slightly with age, and males generally have a larger brain volume than females. The remaining phenotypic variance of cerebellar volume is largely genetic (88%). These genetic factors partly overlap with the genetic factors that explain variance in intracranial space and body height. The applied method is presented as a general approach for the analysis of intermediate phenotypes in which the effects of correlated variables on the observed scores are modeled through multivariate analysis.

An analytic solution to single nucleotide polymorphism error-detection rates in nuclear families: implications for study design.

Recently, there has been increased interest in using Single Nucleotide Polymorphisms (SNPs) as a method for detecting genes for complex traits. SNPs are diallelic markers that have the potential to be inexpensively produced using chip technology. It has been suggested that SNPs will be beneficial in study designs that utilize trio data (father, mother, child). In our previous work, we calculated the probability of detecting Mendelian errors at a SNP locus for a trio randomly selected from a population in Hardy-Weinberg equilibrium. The highest error-detection rate was 30%. Here we investigate the error-detection rate when additional sibs are genotyped. We define an error to be a change from a 1 allele to a 2 allele, or vice versa. Typing one additional sib increases the detection rate on average by 10-13%. Typing two additional sibs increases the detection rate on average by 14-19%. The increase in the detection rate is dependent on the allele frequencies. Equal allele frequencies produce the lowest detection rates, independent of true error rates and number of offspring genotyped. Typing additional siblings not only improves error-detection rates, but can also provide additional linkage information. In order to increase linkage information and error-detection rates, at least two additional siblings should be ascertained when available.

Human Mitochondrial Complex I in Health and Disease

The authors are very grateful to Prof. Rob Sengers and Prof. Frans Trijbels, who founded the Nijmegen Center for Mitochondrial Disorders >20 years ago and who supported us throughout this large-scale project. We cordially thank all the Ph.D. students (Jan Loeffen, Ralf Triepels, Markus Schuelke, Sandy Budde, and Marieke Coenen) and technicians (Roel Smeets, Carin Buskens, Antoon Janssen, and Frans van den Brand) for their enthusiasm and the work they performed in achieving this first part of our research program. The Prinses Beatrix Fonds, the Stichting voor Kinderen die willen maar niet kunnen, and the Fonds Beoefening Wetenschap of the Nijmegen Children's Hospital are gratefully acknowledged for their financial support.

Variations in microfilariae and infective stages of two types of Wuchereria bancrofti from the Thai-Myanmar border

Comparative morphometric and morphological studies of microfilariae and infective stages were undertaken in nocturnally periodic and subperiodic Wuchereria bancrofti. For microfilariae, the body dimensions of nocturnally periodic (NP) were significantly smaller than nocturnally subperiodic (NSP), i.e., body length 268.03+/-14.75 microm (NP), 307.61+/-11.52 microm (NSP); cephalic space length 4.21+/-0.62 microm (NP), 5.32+/-0.79 microm (NSP); head to nerve ring 49.39+/-5.43 microm (NP), 57.40+/-4.46 microm (NSP); innenkörper length 33.05+/-5.89 microm (NP), 44.02+/-8.71 microm (NSP); cephalic space width 4.28+/-0.59 microm (NP), 6.04+/-0.68 microm (NSP); body width at nerve ring 5.01+/-0.57 microm (NP), 7.45+/-0.75 microm (NSP). The number of nuclei between the cephalic space and nerve ring of NP (66.67+/-5.19) was also significantly less than in NSP (94.74+/-6.95). For infective stages, the body dimensions of NP were significantly smaller than NSP, i.e., body length 1632.50+/-131.48 microm (NP), 2002.63+/-222.60 microm (NSP); head to nerve ring 103.09+/-7.47 microm (NP), 122.44+/-9.62 microm (NSP); head to oesophago-intestinal junction 567.69+/-94.84 microm (NP), 666.75+/-110.08 microm (NSP); body width at oesophago-intestinal junction 23.15+/-1.55 microm (NP), 26.78+/-1.62 microm (NSP). It is too early to infer the NP type as an additional sibling species of W. bancrofti but it is reasonable to treat it as a new variety and additional work is needed to clarify its status.

Variations in microfilariae and infective stages of two types of Wuchereria bancrofti from the Thai-Myanmar border

Comparative morphometric and morphological studies of microfilariae and infective stages were undertaken in nocturnally periodic and subperiodic Wuchereria bancrofti. For microfilariae, the body dimensions of nocturnally periodic (NP) were significantly smaller than nocturnally subperiodic (NSP), i.e. body length 268.03 ± 14.75 μm (NP), 307.61 ± 11.52 μm (NSP); cephalic space length 4.21 ± 0.62 μm (NP), 5.32 ± 0.79 μm (NSP); head to nerve ring 49.39 ± 5.43 μm (NP), 57.40 ± 4.46 μm (NSP); innenkörper length 33.05 ± 5.89 μm (NP), 44.02 ± 8.71 μm (NSP); cephalic space width 4.28 ± 0.59 μm (NP), 6.04 ± 0.68 μm (NSP); body width at nerve ring 5.01 ± 0.57 μm (NP), 7.45 ± 0.75 μm (NSP). The number of nuclei between the cephalic space and nerve ring of NP (66.67 ± 5.19) was also significantly less than in NSP (94.74 ± 6.95). For infective stages, the body dimensions of NP were significantly smaller than NSP, i.e. body length 1632.50 ± 131.48 μm (NP), 2002.63 ± 222.60 μm (NSP); head to nerve ring 103.09 ± 7.47 μm (NP), 122.44 ± 9.62 μm (NSP); head to oesophago-intestinal junction 567.69 ± 94.84 μm (NP), 666.75 ± 110.08 μm (NSP); body width at oesophago-intestinal junction 23.15 ± 1.55 μm (NP), 26.78 ± 1.62 μm (NSP). It is too early to infer the NP type as an additional sibling species of W. bancrofti but it is reasonable to treat it as a new variety and additional work is needed to clarify its status.

A New Variation on an Old Theme: Subtleties of the Smith-Lemli-Opitz Syndrome (RSH/SLOS)

SLO is a well-characterized autosomal recessive disorder of cholesterol biosynthesis with a classical phenotype that is distinctive and easily recognizable. However, it was not until the recent recognition of the biochemical abnormality that existence of the mild phenotype could be confirmed. Five individuals with biochemically proven mild or “variant” SLO have been described with 7-DHC levels that are intermediate between those measured in classical SLO patients and controls. The variant phenotype also seems to be characterized by cholesterol levels within or just below the normal range, while classical patients are clearly cholesterol-deficient. We now report three additional siblings, products of a first cousin mating, who have clinical and biochemical findings consistent with variant SLO. The oldest, a 12-year-old girl, has microcephaly, mild facial dysmorphism and moderate 2-3 syndactyly of the feet. Her past history is significant for failure to thrive, mild global developmental delay and behavioral problems, including ADD. 7-DHC and cholesterol levels were 64 uM (controls <10) and 2.7 mM (controls 3.0 - 4.6), respectively. Her 7-year-old brother has microcephaly, a cleft lip, a unilateral single transverse palmar crease and mild 2-3 syndactyly of his feet. He has not been ascertained as a child with developmental delay or behavioral problems. Interestingly, his plasma 7-DHC level was just above the control range at 10 uM and his plasma cholesterol level was just within the control range at 3.0 mM. We are currently repeating these measurements on a second sample. The youngest child, 5 year old boy, has microcephaly, characteristic facial dysmorphism, a left single transverse palmar crease as well as mild 2-3 syndactyly of his feet. He has a clear history of developmental delay and behavioural problems. His plasma 7-DHC was 52 and 24 uM on two separate occasions and his plasma cholesterol was 2.9 both times. These children help to further delineate and improve recognition of the mild/variant SLO phenotype, which may account for a substantial percentage of children with minimal dysmorphism, microcephaly and developmental delay.

Covert video recordings of life-threatening child abuse — lessons for child protection

Objective. To describe historic markers and clinical observations of life-threatening child abuse as diagnosed using covert video surveillance (CVS). Design. A descriptive, retrospective, partially controlled case study. Setting. Two hospitals (in London and North Staffordshire, UK) receiving referrals for the investigation of apparent life-threatening events (ALTE), with the availability of CVS. Patients. A total of 39 children (age range at CVS, 2 to 44 months; median, 9 months) in whom hospital CVS was used to investigate suspicions of induced illness. Thirty-six were referred for investigation of ALTE, one with suspected epilepsy, one with failure to thrive, and one with suspected strangulation. A control group consisted of 46 children with recurrent ALTE proven on physiologic recordings to be attributable to a natural medical cause (9 attributable to epileptic seizures, and 37 attributable to respiratory problems). Intervention. Collection of historic details from medical, social service, and police records; interagency collaboration in planning, investigations, and management; development and use of CVS as a clinical tool in the investigation of patients in whom there was suspicion of induced illness. Outcome. Confirmation of attempted suffocation or other child abuse from CVS. Results. CVS revealed abuse in 33 of 39 suspected cases, with documentation of intentional suffocation observed in 30 patients. Poisonings (with disinfectant or anticonvulsant), a deliberate fracture, and other emotional and physical abuse were also identified under surveillance. The first ALTE occurred at a median age corrected for the expected date of delivery of 3.6 months in the CVS patients and of 0.3 months in controls. Three CVS patients and 27 of the control children (including 20 at The 39 patients undergoing CVS had 41 siblings, 12 of whom had previously died suddenly and unexpectedly. Eleven of the deaths had been classified as sudden infant death syndrome but after CVS, four parents admitted to suffocating eight of these siblings. One additional sibling who had died suddenly with rotavirus gastroenteritis was reinvestigated after CVS of her sister revealed poisoning, and death was found to be caused by deliberate salt poisoning. Other signs of abuse were documented in the medical, social, and police records of an additional 15 of the siblings. In the 52 siblings of the 46 controls, 2 had died: one from hypoplastic left heart at 5 days and the other suddenly and unexpectedly (classified as sudden infant death syndrome) at 7 weeks. Twenty-three of the abusive parents were diagnosed by a psychiatrist as having personality disorders. Conclusions. Induced illness is a severe form of abuse that may cause death or permanent neurologic impairment. It may be accompanied by other severe forms of abuse, may result in behavioral disorders, and may be accompanied by immeasurable suffering. Detection of this abuse requires careful history-taking; thorough examination of the health, social, and police records; and close and focused collaboration between hospital and community child health professionals, child psychiatrists, social workers, and police officers. CVS may help investigate suspicions and ensure that children are protected from additional abuse. When parents have failed to acknowledge that they have deceived health professionals, partnership with them in seeking to protect their children may be neither safe nor effective.

Covert video recordings of life-threatening child abuse: lessons for child protection.

To describe historic markers and clinical observations of life-threatening child abuse as diagnosed using covert video surveillance (CVS). A descriptive, retrospective, partially controlled case study. Two hospitals (in London and North Staffordshire, UK) receiving referrals for the investigation of apparent life-threatening events (ALTE), with the availability of CVS. A total of 39 children (age range at CVS, 2 to 44 months; median, 9 months) in whom hospital CVS was used to investigate suspicions of induced illness. Thirty-six were referred for investigation of ALTE, one with suspected epilepsy, one with failure to thrive, and one with suspected strangulation. A control group consisted of 46 children with recurrent ALTE proven on physiologic recordings to be attributable to a natural medical cause (9 attributable to epileptic seizures, and 37 attributable to respiratory problems). Collection of historic details from medical, social service, and police records; interagency collaboration in planning, investigations, and management; development and use of CVS as a clinical tool in the investigation of patients in whom there was suspicion of induced illness. Confirmation of attempted suffocation or other child abuse from CVS. CVS revealed abuse in 33 of 39 suspected cases, with documentation of intentional suffocation observed in 30 patients. Poisonings (with disinfectant or anticonvulsant), a deliberate fracture, and other emotional and physical abuse were also identified under surveillance. The first ALTE occurred at a median age corrected for the expected date of delivery of 3.6 months in the CVS patients and of 0.3 months in controls. Three CVS patients and 27 of the control children (including 20 at <32 weeks' gestation) were born prematurely. Bleeding from the nose and/or mouth was reported in 11 of the 38 patients with ALTE undergoing CVS but in none of the 46 controls. Four patients who had been subjected to recurrent suffocation before CVS had permanent neurologic deficits and/or required anticonvulsant therapy for epileptic seizures resulting from hypoxic cerebral injury. The 39 patients undergoing CVS had 41 siblings, 12 of whom had previously died suddenly and unexpectedly. Eleven of the deaths had been classified as sudden infant death syndrome but after CVS, four parents admitted to suffocating eight of these siblings. One additional sibling who had died suddenly with rotavirus gastroenteritis was reinvestigated after CVS of her sister revealed poisoning, and death was found to be caused by deliberate salt poisoning. Other signs of abuse were documented in the medical, social, and police records of an additional 15 of the siblings. In the 52 siblings of the 46 controls, 2 had died: one from hypoplastic left heart at 5 days and the other suddenly and unexpectedly (classified as sudden infant death syndrome) at 7 weeks. Twenty-three of the abusive parents were diagnosed by a psychiatrist as having personality disorders. Induced illness is a severe form of abuse that may cause death or permanent neurologic impairment. It may be accompanied by other severe forms of abuse, may result in behavioral disorders, and may be accompanied by immeasurable suffering. Detection of this abuse requires careful history-taking; thorough examination of the health, social, and police records; and close and focused collaboration between hospital and community child health professionals, child psychiatrists, social workers, and police officers. CVS may help investigate suspicions and ensure that children are protected from additional abuse. When parents have failed to acknowledge that they have deceived health professionals, partnership with them in seeking to protect their children may be neither safe nor effective.

Accurate Inference of Relationships in Sib-Pair Linkage Studies

Relative-pair designs are routinely employed in linkage studies of complex genetic diseases and quantitative traits. Valid application of these methods requires correct specification of the relationships of the pairs. For example, within a sibship, presumed full sibs actually might be MZ twins, half sibs, or unrelated. Misclassification of half-sib pairs or unrelated individuals as full sibs can result in reduced power to detect linkage. When other family members, such as parents or additional siblings, are available, incorrectly specified relationships usually will be detected through apparent incompatibilities with Mendelian inheritance. Without other family members, sibling relationships cannot be determined absolutely, but they still can be inferred probabilistically if sufficient genetic marker data are available. In this paper, we describe a simple likelihood ratio method to infer the true relationship of a putative sibling pair. We explore the number of markers required to accurately infer relationships typically encountered in a sib-pair study, as a function of marker allele frequencies, marker spacing, and genotyping error rate, and we conclude that very accurate inference of relationships can be achieved, given the marker data from even part of a genome scan. We compare our method to related methods of relationship inference that have been suggested. Finally, we demonstrate the value of excluding non-full sibs in a genetic linkage study of non-insulin-dependent diabetes mellitus.

Regressive logistic modeling of familial aggregation for asthma in 7,394 population-based nuclear families.

The aim of this population-based study was to determine whether asthma aggregates in families, and if so, whether aggregation was consistent with environmental and/or genetic etiologies. Data were from 7,394 nuclear families (41,506 individuals) from the 1968 Tasmanian Asthma Survey, in which all Tasmanian schoolchildren born in 1961 were surveyed by respiratory questionnaire completed by their parents. Similar data were obtained for parents and siblings of probands. For a child, having ever had asthma was predicted by a parent or sibling having ever had asthma; odds ratio (OR) = 3.13 (95% confidence interval [CI] 2.82-3.48) for mother, 2.99 (2.69-3.32) for father, and 3.47 (3.23-3.72) for a sibling. Regressive logistic modeling showed that, in addition to parent-offspring effects, the data were consistent with the existence of an unmeasured factor shared by siblings, evident in 15% (SE 2%) of families and associated with a conditional OR of 9.68 (8.27-11.32). Familial aggregation was best described by a general oligogenic model with non-Mendelian transmission probabilities. Of the Mendelian models, a codominant model with an allele frequency of 16% (SE 0.3%) was preferred. Under a dominant model there was evidence for additional parent-offspring and sibling effects of similar magnitude. It is unlikely that there is one major loci influencing asthma susceptibility; the overall effects of asthma genes in the population are more likely to be inherited codominantly, at least for the majority of loci of major etiological importance. The role of environmental factors in explaining part of familial aggregation for asthma cannot be ruled out, as major triggers of asthma attacks are familial.

Family size and age at menarche in athletes.

The association between family size and age at menarche was evaluated in 370 university athletes representing seven sports, 291 white and 79 black. Age at menarche, number of children in the family (family size), and birth order were collected retrospectively by questionnaire with a follow-up interview if necessary. The effect of family size on menarche was estimated with linear regression and multiple regression. For each additional sibling in the family-age at menarche was later by 0.17 yr in white athletes, 0.21 yr in black athletes, and 0.16 yr in the total sample (about 2.0-2.5 months). The slopes for white (beta = 0.167) and black (beta = 0.208) athletes did not differ significantly. Controlling for the effects of birth order significantly increased the family size effect in white athletes (beta = 0.221), but not in black athletes (beta = 0.203) or in the total sample (beta = 0.164). The slopes for white and black athletes, after controlling for birth order, also did not significantly differ. Thus, after controlling for birth order, menarche was later by 0.16-0.22 yr (about 2.0-2.6 months) for each additional sibling in the family, which was within the range of family size effects observed in samples of nonathletes and athletes. The family size effect also persists after controlling for maternal age at menarche in a subsample of 134 athletes, thus implying an independent effect of family size. Later ages at menarche observed in athletes may thus be due in part to larger family sizes.