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PubMed1994

Prenatal gender preference of mothers of feminine and masculine boys: relation to sibling sex composition and birth order.

A mother's (prenatal) wish for a girl has, at times, been implicated as an etiological factor for boyhood femininity or its DSM-III-R diagnostic equivalent, the Gender Identity Disorder of Childhood. In one sample of 52 feminine and 52 nonclinical control boys from Los Angeles, the proportion of mothers who recalled a wish for a girl during the pregnancy did not differ significantly between groups (26.9% vs. 19.2%, respectively); however, in both groups, the maternal wish for a girl was significantly more common in sibships in which all of the proband's older siblings were male. In a second sample of 103 feminine boys from Toronto, the maternal wish for a girl was significantly higher than that found in the Los Angeles sample (43.7% vs. 26.9%), but a control group was not available; as in the Los Angeles sample, the maternal wish for a girl was significantly more common in sibships in which all of the proband's older siblings were male. Implications of these findings for further study of maternal influences on boyhood femininity are discussed.

Birth Order↗
PubMed2000

Multipoint linkage analysis of a candidate gene locus in rheumatoid arthritis demonstrates significant evidence of linkage and association with the corticotropin-releasing hormone genomic region.

OBJECTIVE: Rheumatoid arthritis (RA) is the most common disabling autoimmune disease, affecting approximately 1% of the population. The disease etiology is unknown, but it involves inflammation and immune dysregulation and is influenced by genetic variation at both HLA and other, as-yet-unidentified genetic loci. Corticotropin-releasing hormone (CRH; or corticotropin-releasing factor), a primary regulator of the hypothalamic-pituitary-adrenal axis and a key element in the response to stress and inflammation, is a strong candidate gene for RA. We examined the role of DNA variation across the region containing this gene in multicase families with RA. METHODS: We genotyped fluorescently labeled simple tandem repeat genetic markers from chromosome 8q13 in 295 families with multiple cases of RA. Singlepoint and multipoint nonparametric linkage analysis and association analysis using transmission disequilibrium testing (TDT) were also used. RESULTS: Single-point linkage analysis using a microsatellite within 30 kb of the CRH locus (CRH.PCR at position 8q13) showed a significant excess of allele sharing in 295 United Kingdom RA families with at least 2 affected members (MapMaker/Sibs logarithm of odds [LOD] 1.4; P = 5.5x10(-3); mean identity by descent [ibd] sharing 55.9%). To provide a more detailed linkage map, a multipoint analysis was conducted with an additional 7 dinucleotide microsatellite markers (average heterozygosity 0.75) flanking the CRH locus. Significant linkage was detected over a 22-cM region between D8S285 and D8S530, with the maximum singlepoint LOD score of 1.77 at D8S1723 (MapMaker/Sibs P = 2.2x10(-3); mean ibd sharing 59.3%). Multipoint analysis showed strongest evidence for linkage at the same marker (multipoint LOD 1.78, P = 2.1x10(-3), mean ibd sharing 55.8%). TDT analysis showed significant association at the CRH locus (P = 2.6x10(-3)). CRH has a sibling relative risk of 1.14, and contributes <10% to the sibling relative risk of RA. CONCLUSION: With the exception of HLA, this is the strongest evidence yet of a genetic locus that is both linked to and associated with RA, and provides an avenue for further genetic characterization and potentially novel therapeutic intervention.

Adult↗
PubMed1991

Sibling and environmental correlates of young adults' status attainment.

This study used longitudinal data to investigate associations among sibling-related variables, adolescents' perceptions of family and school learning environments, and social-status attainment measures, for 300 young Australian adults from different social-status groups. The findings indicated that: (a) sibling-related variables continued to have a number of significant associations with young adults' social-status attainment after taking into account mediating relationships between adolescents' learning environments and the attainment measures, and (b) these relationships between sibling and attainment measures varied for young adults from different social-status groups.

Achievement↗
PubMed2004

Viability of Iberian x Meishan F2 newborn pigs. II. Survival analysis up to weaning.

Iberian x Meishan F2 piglet's preweaning survivability was analyzed using categorical data regression procedures within the proportional hazards assumption. A frailty sire model was assumed with the litter effect treated as an additional random source of variation. Moreover, the relative birth weight within litter and the litter effect were considered time-dependent covariates that changed their values in the second day of life due to cross fostering carried out to standardize litters. Six variables had a significant effect on survivability: birth weight (P < 0.01), relative birth weight within litter (P < 0.001), rectal temperature 60 min after birth (P < 0.01), type of presentation at birth (P < 0.05), presence of stillbirths (P < 0.001), and presence of mummified fetuses (P < 0.001). Small piglets (<0.98 kg) suffered a high hazard ratio (6.57; P < 0.001), with this variable being clearly lower for the rest of birth weight categories. Piglets that were small in relation to their siblings (relative birth weight within litter) also suffered an increased death risk, with a hazard ratio of 1.81 (P < 0.05), which was similar to animals with posterior presentations at birth (hazard ratio = 1.80; P < 0.05). Piglets with a rectal temperature lower than 35.4 degrees C 60 min after birth showed the highest hazard ratio (7.18; P < 0.01). Furthermore, the presence of mummified fetuses decreased the survivability of the remaining siblings, with a hazard ratio of 2.03 (P < 0.01), as did the presence of stillbirths (hazard ratio = 3.55; P < 0.001). The inclusion of the two random effects allowed us to estimate the mode of the joint posterior density of the sire variance (0.08) and the litter variance (1.98). The estimated heritability of preweaning survival reached a value of 0.03. We conclude that piglet survival involves several systematic influences related to birth weight, thermoregulatory ability, and injuries suffered during gestation and farrowing. The genetic variance was small compared with those generated by the common environment, for which the genetic improvement of piglet survival seems difficult.

Animals↗
PubMed2003

Siblings and theory of mind in deaf native signing children.

We report a study designed to examine the basis of "theory of mind" (ToM) reasoning in deaf children who are native signers of British Sign Language. The participants were 20 native signers (aged 4-8 years) and their siblings. The children were given a measure of the quality of sibling relations together with a referential communication test concerning physical representations of objects and people. Sibling quality as perceived by siblings predicted children's ToM scores over and above age and referential communication. We conclude that the process of ToM understanding is linked to positive sibling relations that may permit access to knowledge about the inner worlds of beliefs and other mental states.

Journal Article↗
PubMed2000

Bootstrap confidence intervals for relative risk parameters in affected-sib-pair data.

In affected-sib-pair (ASP) studies, parameters such as the locus-specific sibling relative risk, lambda(s), may be estimated and used to decide whether or not to continue the search for susceptibility genes. Typically, a maximum likelihood point estimate of lambda(s) is given, but since this estimate may have substantial variability, it is of interest to obtain confidence limits for the true value of lambda(s). While a variety of methods for doing this exist, there is considerable uncertainty over their reliability. This is because the discrete nature of ASP data and the imposition of genetic "possible triangle" constraints during the likelihood maximization mean that asymptotic results may not apply. In this paper, we use simulation to evaluate the reliability of various asymptotic and simulation-based confidence intervals, the latter being based on a resampling, or bootstrap approach. We seek to identify, from the large pool of methods available, those methods that yield short intervals with accurate coverage probabilities for ASP data. Our results show that many of the most popular bootstrap confidence interval methods perform poorly for ASP data, giving coverage probabilities much lower than claimed. The test-inversion, profile-likelihood, and asymptotic methods, however, perform well, although some care is needed in choice of nuisance parameter. Overall, in simulations under a variety of different genetic hypotheses, we find that the asymptotic methods of confidence interval evaluation are the most reliable, even in small samples. We illustrate our results with a practical application to a real data set, obtaining confidence intervals for the sibling relative risks associated with several loci involved in type 1 diabetes.

Confidence Intervals↗
PubMed1997

Linkage analysis of complex traits using affected sibpairs: effects of single-locus approximations on estimates of the required sample size.

We investigated the power of the affected sibpair method for detecting a disease locus when the disease is inherited through two bi-allelic loci. The power was computed for all possible values of the gene frequencies and penetrances that lead to a given population prevalence and a given sibling relative risk. A method to generate rapidly all possible models that give a specific population prevalence and relative risk is provided. We applied it to the case of a two-locus disease with a prevalence of 10% and a low sibling relative risk of 1.5. For this particular example, regardless of the true underlying model, a sample size (N = 450 for alpha = 0.05, N = 1,500 for alpha = 0.0001) may be determined such that one would expect enough power (0.80) to detect at least one of the two disease genes. In addition to the general case, we examined a special class of models in which the marginal penetrances at each locus are either recessive or dominant. In this instance, the gene frequencies were excellent predictors of the power afforded by a particular sample size. These methods have been implemented in a C program called SIBPOWER which is freely available from the first author. With this program, investigators can perform their own power calculations for any two-locus model of their choice thus avoiding the need to use single-locus approximations that may grossly underestimate the necessary sample size.

Gene Frequency↗
PubMed2006

Testing for genetic heterogeneity in the genome search meta-analysis method.

The Genome Search Meta-Analysis (GSMA) method is widely used to detect linkage by pooling results of previously published genome-wide linkage studies. The GSMA uses a non-parametric summed rank statistic in 30 cM bins of the genome. Zintzaras and Ioannidis ([2005] Genet. Epidemiol. 28:123-137) developed a method of testing for heterogeneity of evidence for linkage in the GSMA, with three heterogeneity statistics (Q, Ha, B). They implement two testing procedures, restricted versus unrestricted for the summed rank within the bin. We show here that the rank-unrestricted test provides a conservative test for high heterogeneity and liberal test for low heterogeneity in linked regions. The rank-restricted test should therefore be used, despite the extensive simulations needed. In a simulation study, we show that the power to detect heterogeneity is low. For 20 studies of affected sib pairs, simulated assuming linkage in all studies to a gene with sibling relative risk of 1.3, the power to detect low heterogeneity using the Q statistic was 14%. With linkage present in 50% of the studies (to a gene with sibling relative risk of 1.4), the Q heterogeneity statistic had power of 29% to detect high heterogeneity. The power to detect linkage using the summed rank was high in both of these situations, at 98% and 79%, respectively. Although testing for heterogeneity in the GSMA is of interest, the currently available method provides little additional information to that provided by the summed rank statistic.

Genetic Heterogeneity↗
PubMed1997

Risk of recurrence of birth defects in Washington State.

A population-based study was conducted using maternally-linked birth certificate records from Washington State for 1980-93 to evaluate the risk of birth defect occurrence among infants with previously affected siblings, relative to infants whose siblings did not have birth defects. The risks of recurrence of similar and dissimilar defects were estimated, and the effects of change in paternity and/or city of residence were evaluated as proxies of genetic and environmental effects. At the first birth on record, 3322 women were identified in the linked certificates as giving birth to a child with a birth defect; 6620 women whose first birth did not result in an infant with a defect were randomly selected for comparison. Women with a malformed infant had an increased risk of having a malformed infant at the subsequent birth (Relative Risk = 1.9, [95% Confidence Interval (CI) = 1.5-2.4]), which did not vary by intervening changes in partner or residence. The risk of recurrence of the same general type of defect [RR = 11.7, 95% CI = 9.7-19.50] was much greater than that of occurrence of a dissimilar defect [RR = 1.5, 95% CI = 1.1-1.9]. This was consistent for all defect categories, and did not vary markedly by changes in partner or residence.

Birth Order↗
PubMedDate not supplied

An adoption study of the etiology of teacher and parent reports of externalizing behavior problems in middle childhood.

Twin studies of externalizing behavior problems in middle childhood and early adolescence suggest that there is moderate-to-substantial genetic variance and modest-to-moderate shared environmental variance in these behaviors. The present study is novel in three ways: it is a sibling adoption study, it employs both teacher and parent ratings of children's behaviors averaged over five assessments, and it explores aggression and delinquency separately. The sample included 78 adoptive sibling pairs and 94 biologically related sibling pairs in the Colorado Adoption Project. Parents and teachers completed ratings of the children's externalizing behavior problems at ages 7, 9, 10, 11, and 12 years. Boys and adopted children were rated as being somewhat higher in externalizing behavior problems. Sex differences in delinquency were more pronounced in adoptive than in nonadoptive families. Teachers' ratings showed evidence for moderate heritability and no shared environment for aggression and showed modest shared environment for delinquency. Parents' ratings showed evidence for moderate amounts of heritability and shared environment for both aggression and delinquency.

Adoption↗
PubMed2005

Heritability of refractive error and familial aggregation of myopia in an elderly American population.

PURPOSE: To determine the heritability of refractive error and the familial aggregation of myopia in an older population. METHODS: Seven hundred fifty-nine siblings (mean age, 73.4 years) in 241 families were recruited from the Salisbury Eye Evaluation (SEE) Study in eastern Maryland. Refractive error was determined by noncycloplegic subjective refraction (if presenting distance visual acuity was < or =20/40) or lensometry (if best corrected visual acuity was >20/40 with spectacles). Participants were considered plano (refractive error of zero) if uncorrected visual acuity was >20/40. Preoperative refraction from medical records was used for pseudophakic subjects. Heritability of refractive error was calculated with multivariate linear regression and was estimated as twice the residual between-sibling correlation after adjusting for age, gender, and race. Logistic regression models were used to estimate the odds ratio (OR) of myopia, given a myopic sibling relative to having a nonmyopic sibling. RESULTS: The estimated heritability of refractive error was 61% (95% confidence interval [CI]: 34%-88%) in this population. The age-, race-, and sex-adjusted ORs of myopia were 2.65 (95% CI: 1.67-4.19), 2.25 (95% CI: 1.31-3.87), 3.00 (95% CI: 1.56-5.79), and 2.98 (95% CI: 1.51-5.87) for myopia thresholds of -0.50, -1.00, -1.50, and -2.00 D, respectively. Neither race nor gender was significantly associated with an increased risk of myopia. CONCLUSIONS: Refractive error and myopia are highly heritable in this elderly population.

Aged↗
PubMed2000

Positive consequences of sibling conflict in childhood and adulthood.

The present article was an attempt to integrate the two disparate literatures on sibling conflict in childhood and adulthood with a particular emphasis on the potential benefits of conflictual sibling relations for adult well-being and competence. The extant literature on children's sibling conflicts underscores that conflictual exchanges may actually be related to increases in children's social and emotional competence, the development of self and identity formation, sibling relationship quality, and the subsequent parenting of one's own children. We presented descriptive data bearing on similar categorical benefits from our interviews with middle-aged and older adults with respect to sibling conflict in childhood and adulthood. Based on these findings, we recommend that future research on adult social relations should seriously consider the many ways in which challenge, conflict, and adversity in social relationships may contribute to developmental outcomes, both "good" and "bad."

Adult↗
PubMed1990

Relationship classification using grade of membership analysis: a typology of sibling relationships in later life.

The results of a comparison of two typologies of sibling relationships in old age are reported. Both analyses rely on the same data collected in individual interviews with adults over the age of 65. The first typology was constructed using constant comparative analysis; the second relied on the grade of membership (GOM) technique. This is the first time GOM has been used to create a taxonomy of human relationships based on psychosocial variables. The two typologies are compared in terms of number of types generated, the characteristics of each type, factors influencing typological construction, and the utility of empirical results. Implications for additional use of the GOM technique to study late-life sibling relations are discussed.

Aged↗