Sibling Correlations Research Articles

Cross-trait familial resemblance for body fat and blood lipids: familial correlations in the Quebec Family Study.

In an attempt to better understand the genetic basis of the metabolic syndrome, we have undertaken a series of studies on the familial aggregation in the clustering of the coronary heart disease risk factors which characterize this syndrome. In the present study, the hypothesis of shared genetic (pleiotropy) and/or environmental factors between body fat and blood lipids is investigated by examining cross-trait (eg, father's body fat with his son's blood lipid) familial resemblance between 4 indicators of body fat (body mass index [BMI], sum of 6 skin folds [SF6]) and fat distribution (the ratio of the trunk to extremity skin folds adjusted [TER-sf] and unadjusted [TER] for SF6), and 5 blood lipid variables (total cholesterol [CH], triglycerides [TG], cholesterol associated with high-density lipoproteins [HDL], the CH/ HDL ratio and the difference between CH and HDL [CH-HDL]) measured in 1239 individuals from 309 families participating in the Quebec Family Study. A bivariate correlation model was used to obtain maximum likelihood estimates of cross-trait spouse, parent-offspring, and sibling correlations after adjustment of body fat and lipid data for the effects of age, separately in the four sex-by-generation groups. Likelihood ratio tests revealed the presence of significant (P < .05) cross-trait resemblance between body fat (BMI and SF6) and all lipid traits except CH and also between fat distribution (TER and TER-sf) and CH/HDL and CH-HDL. Only sibling cross-trait correlations were significant for all body fat-lipid pairs of measures, with bivariate familiality estimates (i.e., shared genetic and/or environmental factors) ranging from 8% to 40%. Although the hypothesis of genetic pleiotropy cannot be ruled out from the pattern of cross-trait correlations found in the present study, we conclude that environmental factors shared within sibships are probably more important than common genes in determining the covariation between body fat and blood lipids.

Familial resemblance of plasma lipids, lipoproteins and postheparin lipoprotein and hepatic lipases in the HERITAGE Family Study.

The familial aggregation of lipids and lipoproteins and plasma postheparin triglyceride lipases was investigated in 86 Caucasian families participating in the HERITAGE Family study, a study investigating the role of genetic factors in the adaptation to exercise training and its relationships with cardiovascular disease risk factors. Accordingly, sedentary subjects were recruited, tested for a battery of measurements, exercise trained for 20 weeks, and were re-measured. The present report includes plasma levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides, and postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities measured in 437 sedentary individuals (171 parents and 266 adult offspring) before training. Significant familial resemblance was observed for all the age-adjusted phenotypes. The pattern of familial correlations reveals no spouse correlations but significant parent-offspring and sibling correlations for total cholesterol, HDL-cholesterol and LDL-cholesterol with heritability (h2) estimates of 62%, 83%, and 50%, respectively. For plasma triglyceride concentrations (h2 = 55%) and HL activity (h2 = 40%), significant spouse correlations were found in addition to parent-offspring and sibling correlations, suggesting that common familial environment in addition to genetic factors contribute to the familial resemblance. For plasma LPL activity, there was no spouse correlation, but sex differences were found in the familial correlations with higher heritabilities in female pairs (h2 = 76%) compared to male pairs (h2 = 30%) and opposite-sex pairs (h2 = 44%). These results confirm the findings of previous family studies showing that genetic factors are major determinants of the familial resemblance in plasma lipids and lipoproteins and suggest the presence of sex differences in the heritability of postheparin LPL activity.

THE FAMILIAL TRANSMISSION OF CRIMINAL CONVICTIONS*

This article examines the familial transmission of criminal convictions in families in the Cambridge Study in Delinquent Development. Our main analyses focus on the 344 families in the Cambridge Study with two or more children. Criminal convictions were highly familial because convictions in a parent increased the risk of convictions in a child. Correlations between siblings were stronger in same‐sex siblings (.45 to .50) than in opposite‐sex ones (.27). Sibling correlations did not vary by birth order. Convictions of mothers and father correlated .55. Parent‐child correlations were about the same as within‐generation correlations between siblings. LISREL models were used to assess whether the effect of parental convictions on child convictions was direct or mediated through the quality of the family environment (i.e., supervision. child rearing, and family size). The best fitting LISREL models suggested a direct effect of parental convictions on child convictions, without any mediation by family environment. These data on fill biological siblings, however, did not permit separate estimation of family environmental versus genetic effects. One environmental effect appeared, however—a socialization effect among siblings; in families with three sons, there appeared to be mutual influence of one sibling on another. Also, regression models based on the boys suggested that family environmental variables did add to parental criminality.

Age variations in sibling correlations for height, sitting height and weight

SummaryFamilial correlations for height, sitting height and weight have been studied in a sample of 1278 siblings for the Biscay province (Basque Country), aged 4+ to 24+ years. The data have been internally standardized according to sex and age of the individuals. The degree of resemblance among sibling has been expressed by intraclass correlation coefficients. The total sample has been divided into three age categories: <12 years, 12–15 years, and ≥15 years, in order to examine the effect of age on sibling correlations. In general, changes with age have been observed: sibling correlations for height show a clear upward trend through the considered growth period, reaching a value of 0·48 from 15 years of age. Intra-correlations for weight show a slight downward trend with age. Sitting height shows a rather low correlation before 12 years of age, but equally high values in the other two ranges of age (0·48 and 0·47, respectively). This study confirms that the sibling resemblance for the analysed traits fluctuated through the growth period—height and sitting height showing similar patterns of variation with age—and that, after puberty, the degree of genetic determination is higher for bone measurements than for weight.

Adult family members and their resemblance of coronary heart disease risk factors: the Cardiovascular Disease Study in Finnmark.

Coronary heart disease tends to run in families, and the familial resemblance of major risk factors for the disease was examined among various types of adult family members. Family units were assembled from a total of 4,738 men and women who took part in a cross sectional health survey in four Norwegian municipalities where all inhabitants between 20 and 52 years of age were invited. After adjusting for age and other confounders, correlation coefficients were derived as a measure of the degree of resemblance. Viewed across all types of investigated familial relationships, similarity was found to be stronger for total cholesterol than for high-density lipoprotein cholesterol and triglycerides, and also stronger for systolic than for diastolic blood pressure. Between husbands and wives (3,060 subjects), correlations were small (between 0.02 and 0.06), except for 0.11 for total cholesterol. Lipid and blood pressure correlations ranged from 0.13 to 0.27 for parents and their offspring (471 subjects, p < 0.05) and from 0.11 to 0.22 among siblings (2,166 subjects, p < 0.01). Sibling correlations were consistent across age groups. Furthermore, reports from each individual on daily smoking (yes or no) revealed that husbands and wives had similar habits in 63.5% of all marriages as compared with the expected 49.4% had no smoking similarity at all been present. Smoking concordance was also demonstrated among siblings (p < 0.01). The persistent pattern of lipid and blood pressure aggregation among genetically related individuals from 20 to 52 years of age and the much weaker such similarity between husbands and wives, point towards genes or commonly shared environment at early ages as a major reason why coronary heart disease runs in families.

Genetic and environmental factors in relative body weight and human adiposity.

We review the literature on the familial resemblance of body mass index (BMI) and other adiposity measures and find strikingly convergent results for a variety of relationships. Results from twin studies suggest that genetic factors explain 50 to 90% of the variance in BMI. Family studies generally report estimates of parent-offspring and sibling correlations in agreement with heritabilities of 20 to 80%. Data from adoption studies are consistent with genetic factors accounting for 20 to 60% of the variation in BMI. Based on data from more than 25,000 twin pairs and 50,000 biological and adoptive family members, the weighted mean correlations are .74 for MZ twins, .32 for DZ twins, .25 for siblings, .19 for parent-offspring pairs, .06 for adoptive relatives, and .12 for spouses. Advantages and disadvantages of twin, family, and adoption studies are reviewed. Data from the Virginia 30,000, including twins and their parents, siblings, spouses, and children, were analyzed using a structural equation model (Stealth) which estimates additive and dominance genetic variance, cultural transmission, assortative mating, nonparental shared environment, and special twin and MZ twin environmental variance. Genetic factors explained 67% of the variance in males and females, of which half is due to dominance. A small proportion of the genetic variance was attributed to the consequences of assortative mating. The remainder of the variance is accounted for by unique environmental factors, of which 7% is correlated across twins. No evidence was found for a special MZ twin environment, thereby supporting the equal environment assumption. These results are consistent with other studies in suggesting that genetic factors play a significant role in the causes of individual differences in relative body weight and human adiposity.

Familial resemblance in height and weight in an endogamous Hahisya caste population of rural West Bengal

Intrafamilial resemblance and heritability of height and weight in an endogamous, agricultural caste population of rural West Bengal ("Mahisya") were estimated from data for 540 individuals, 110 parent pairs and 187 sons and 133 daughters (children as well as adults) from 110 nuclear families. Multiple regression with age and sex adjustments was used. A trend of greater mother-child than father-child correlation was observed, but was not significant. Sibling correlations indicated no evidence of sex linkage. Heritability for height (h2 = 0.603) was greater than that for weight (h2 = .405). Am. J. Hum. Biol. 9:7-9 © 1997 Wiley-Liss, Inc.

Familial resemblance in height and weight in an endogamous Hahisya caste population of rural West Bengal

Intrafamilial resemblance and heritability of height and weight in an endogamous, agricultural caste population of rural West Bengal ("Mahisya") were estimated from data for 540 individuals, 110 parent pairs and 187 sons and 133 daughters (children as well as adults) from 110 nuclear families. Multiple regression with age and sex adjustments was used. A trend of greater mother-child than father-child correlation was observed, but was not significant. Sibling correlations indicated no evidence of sex linkage. Heritability for height (h2 = 0.603) was greater than that for weight (h2 = .405). Am. J. Hum. Biol. 9:7-9 © 1997 Wiley-Liss, Inc.

The effect of common rearing on adolescent adjustment: Evidence from a U.S. adoption cohort.

The influence of shared environmental factors on adolescent adjustment was investigated in a sample of 667 adoptive families. Correlations between parental ratings of family functioning and adolescent ratings of adjustment were generally higher for birth offspring than for adoptive offspring, suggesting passive genotype-environment processes. For all except one of the indicators of adolescent adjustment, the nonbiological sibling correlation was low, suggesting that approximately 10% or less of the variance in these measures is attributable to shared environmental effects. However, for a quantitative measure of alcohol and tobacco use, the nonbiologically related sibling correlation was moderate (r =.26) but most consistent with sibling rather than parent effects. These findings provide further evidence of the minimal effect of common rearing on sibling psychological similarity, at least within the broadly constituted U.S. middle class.

Familial correlations, cohabitation effects, and heritability for cardiovascular risk factors

Familial correlations in cardiovascular risk factors were investigated with use of data from a community-based sample of 1319 nuclear families involving 4178 adult persons collected in the Busselton Population Health Surveys over the period 1966 to 1981. The risk factors considered were systolic blood pressure, diastolic blood pressure, body mass index, triceps fatfold, and cholesterol. All risk factors showed positive familial correlations, with correlations generally being lower for spouses than for parent-offspring pairs or for siblings. Spouse correlations showed little variation with age, suggesting that observed correlations are primarily due to assortative mating and not to cohabitation. The parent-offspring correlations tended to decline with age of (adult) offspring; this observation suggests that the effect of a shared household environment during childhood and adolescence diminishes over time when living apart during adulthood. The sibling correlations decreased with age for blood pressure and serum cholesterol and increased with age for body mass index and triceps fatfold. The estimated heritabilities were 27% for systolic and diastolic blood pressure, 37% for serum cholesterol, 52% for body mass index, and 23% for triceps fatfold. These results confirm that substantial familial aggregation of cardiovascular risk factors occurs and that much of this aggregation has a genetic basis, although assortative mating (in spouses) and environmental influences (in offspring and siblings) are also present. The nuclear family should be considered as a point of intervention in cardiovascular disease prevention programs.

Familial aggregation of abdominal visceral fat level: Results from the Quebec family study

The purpose of this study was to investigate the importance of familial aggregation in abdominal visceral fat (AVF) level as assessed by computed tomography (CT). Four measures of abdominal adipose tissue, obtained from an abdominal scan between the fourth and fifth Lumbar vertebrae (L4-L5) taken in 366 adult subjects from 100 French-Canadian nuclear families, were considered in this study. Total abdominal fat, AVF, subcutaneous abdominal fat, obtained by computing the difference between total and AVF tissue areas, and the visceral to total abdominal fat ratio were measured. Spouses, parent-offspring, and sibling correlations were computed by maximum likelihood methods after adjustment of the four phenotypes for age and for age and total fat mass (FM) derived from underwater weighing. Significant familial aggregation was found for all phenotypes, whether adjusted or not for body FM. However, after adjustment of data for body FM, in addition to age, all spouse correlations became nonsignificant, suggesting that the familial aggregation of abdominal fat is primarily genetic. Heritability estimates reached 42% and 56% for subcutaneous fat and AVF, respectively. These results suggest that genetic factors are major determinants of the familial aggregation observed in the amount of abdominal fat, irrespective of total body fat content, and that AVF seems more influenced by genetic factors than abdominal subcutaneous adipose tissue. These findings imply that some individuals are more at risk than others to exhibit the various metabolic complications associated with upper-body obesity because of their inherited tendency to store abdominal fat in the visceral depot rather than in the subcutaneous depot.

Familial aggregation of subcutaneous fat patterning: Principal components of skinfolds in the Québec family study.

Familial resemblance was examined for each of the principal components arising from an analysis of six skinfolds (triceps, biceps, subscapular, abdominal, suprailiac, and medial calf) measured in 1,237 participants of the Québec Family Study. Most of the phenotypic variance among the skinfolds (83%) was accounted for by the first two principal components. Examination of the skinfold loadings on each principal component, as well as intraindividual cross-trait correlations with other body composition and fat pattern measures (body mass index; total fat mass and fat-free mass estimated from body density obtained through underwater weighing; the sum of six skinfolds; and the ratio of trunk to extremity skinfolds) support the interpretation of the first component as a general measure of adiposity and the second component as a trunk-extremity contrast. Parent-child and sibling correlations for each of the two principal components indicate that familial effects reach 46% (general) and 52% (trunk-extremity). Although the eigenvalues for the remaining four principal components (accounting for 17% of the variance) are <1.0, it is noteworthy that each exhibits significant familial resemblance (31-60%). Further, the intraindividual correlations for the additional four components with the other body size indicators are quite low, suggesting that they capture somewhat different aspects of relative fat distribution. © 1996 Wiley-Liss, Inc.

Parent and sibling influences on adolescent alcohol use and misuse: evidence from a U.S. adoption cohort.

Although adolescent alcohol use has been consistently associated with parental drinking behavior, sibling drinking behavior and family functioning, the extent to which these associations owe to genetic or shared environmental influences has not been previously investigated. Using an adoption study design, we sought to determine whether the familial correlates of adolescent alcohol involvement were due to common genetic or common environmental effects. The sample consisted of 653 adopted families ascertained through adoption agencies in four U.S. states. Each family consisted of a target adopted adolescent, an adoptive mother and an adoptive father. In addition, 68 birth adolescents (i.e., biological offspring of the adoptive parents) and 187 second adopted adolescents from these families participated in the study. All participants completed a mail survey that included assessment of drinking behavior and family functioning. The relationship between parental problem drinking and adolescent alcohol involvement was moderate and significant among birth offspring (corrected multiple correlation, Rc = .30), but small and non-significant among adoptive offspring (Rc = .00). The relationship between adolescent alcohol involvement and family functioning was substantial for birth offspring (Rc = .39), but only modest for adoptive offspring (Rc = .16). The nonbiological sibling correlation for involvement with alcohol was significant (r = .24) and moderated by sibling pair demographic similarity, such that same-sex, similar-age siblings were substantially more similar (r = .45) than opposite-sex, dissimilar-aged siblings (r = .01). These findings suggest that adolescent alcohol use is affected minimally by the environmental consequences of parent problem drinking and family functioning, but substantially by sibling environmental effects.

Sibling correlations of coronary heart disease risk factors in a sample of Israeli offspring with parental history of myocardial infarction

Sibling correlations for coronary heart disease risk factors were analyzed in 731 pairs of siblings whose parents experienced a first myocardial infarction. Sibling correlations for lipids, lipoproteins and apolipoproteins ranged from 0.29 to 0.48, with limited changes on adjustment for sex, age, education and body mass index. For most lipid variables brother-brother correlation coefficients were highest and sister-brother correlation coefficients were lowest. Sib-sib correlation coefficients for lipids, lipoproteins, blood pressure and body mass index were similar to those estimated from a random sample of Jewish families. The sibling correlations were relatively low for waist to hip ratio, triceps and suprailiac skinfolds, moderate for subscapular skinfolds and body circumference measurements and high for number of cigarettes smoked by the siblings. The sibling correlations for lipid variables showed a moderate dependency on the apolipoprotein B XbaI genotypes. Siblings living in the same household tended to have higher correlation coefficients for HDL-C, apolipoprotein B and apolipoprotein AI than those living apart. The correlation coefficients for number of cigarettes and anthropometric variables tended to be heterogeneous due to the higher correlations among siblings living apart. A clear trend of decline in sib-sib correlations for apolipoprotein AI, glucose, cigarette smoking, body mass index and circumference measurements with increased spacing between sibling's ages was indicated. This temporal trend in sibling correlations for coronary heart disease risk factors suggests that genetic and/or environmental factors may have different influences at different ages.

Properties of Alternative Estimators of Familial Correlations under Variable Sibship Size

Selected distributional properties of a variety of estimators of familial correlations (spouse, parent-child, and sibling) were investigated numerically, focusing particularly on sibling correlations under variable sibship size. Maximum likelihood estimators were evaluated for each of the three familial relationships. An additional parent-offspring estimator was studied using a parent-midoffspring estimate pooled over variable sibship size. For sibling intraclass correlations, three estimators based on analysis of variance and three pairwise estimators using different weighting functions for variable sibship sizes were investigated. Correlations were estimated from data simulated under eight sampling conditions (each replicated 1,000 times) using two sets of true parameter values, moderate and large sample sizes, and normal versus highly non-normal sample distributions of data. The estimators are nearly unbiased and efficient, but none of the sibling correlation estimators are normally distributed in small samples. Estimates from highly non-normal data are nearly unbiased but are less efficient than those from normal data.

Educational and occupational achievements of brothers and sisters in adoptive and biologically related families

The study of brothers and sisters from adoptive and biologically related families permits unique analyses of the determinants of young adults' educational and occupational achievements. Brothers and sisters come from the same homes, neighborhoods, and usually schools. Many differences among families are controlled by the study of siblings. In addition, adoptive families influence their children only through the environment they provide, whereas biologically related parents transmit their intellectual and personal characteristics to their offspring genetically as well. Thus, the comparison of models of adult achievements for children from adoptive and biologically related families can inform us about the true effects of family environments, apart from genetic transmission (Scarr and Weinberg, 1978, 1980). In this follow-up study of 450 biologically related and adopted young adults (ages 22 to 30 years), we report on the family resemblances in educational and occupational achievements. Parents' reports were obtained on 97% of the original sample (N = 443), and 77% of the young adults participated in the follow-up study themselves; complete educational and occupational data were available on 303 young adults. Results show that biological sons are more influenced by their family backgrounds than daughters, regardless of genetic relatedness. A second finding is that young women's achievements are not as predictable from their own earlier achievements as are those of their brothers. A third finding is that parents invest in their sons' educational futures, regardless of sons' abilities and achievements, in ways they do not invest in their daughters' postsecondary educations. Sibling correlations and natural mother-adopted child correlations suggest that test scores, high school performance, postsecondary education, and even later occupational status can be influenced by genetic variability in personal characteristics that affect such achievements.

Evaluation of tuberculin reactivity in BCG-immunized siblings.

The purpose of the present study was to determine in BCG-immunized sibships < or = 14 yr of age whether the correlations of intensity of tuberculin reactivity support a genetic regulation of the response to BCG immunization. The study population consisted of 659 healthy children living in 265 households exposed to an adult with tuberculosis: 38 children did not have a BCG scar, 327 children had one BCG scar, and 294 had two BCG scars from vaccinations at birth and at 6 yr of age. There were 603 full siblings, 16 half-siblings, and 40 unrelated children. Tuberculin testing was performed by one trained nurse. Sibling correlations of the intensity of the tuberculin response were calculated after adjusting for various nongenetic covariates that could be important in predicting it. The sibling correlations were significant at the 1% significance level. There was no significant correlation of tuberculin reactivity among unrelated children in the same household. These results are consistent with genetic regulation of the development and persistence of tuberculin reactivity after BCG immunization.

Sibling correlations and segregation analysis of age-related maculopathy: the Beaver Dam Eye Study.

Sibling correlations were evaluated and segregation analysis was performed on age-dependent maculopathy scores of the right and left eyes of individuals from 564 families in the Beaver Dam Eye study. There is evidence of significant sibling correlations. The data fit a mixture of two normal distributions, especially after undergoing the Box and Cox power transformation. In each eye, the hypothesis of mendelian transmission of a major effect cannot be rejected under the tau AB free model, but is rejected under the tau's free model. The hypothesis of a random environmental major effect is rejected. Similar major gene parameter estimates are found for both eyes. The results are consistent with a major effect accounting for 62% and 59%, in the right and left eyes, respectively, of the determination of age-related maculopathy scores. A single major gene can account for about 89% and 97% of this variability due to a major effect, or for about 55% and 57% of the total variability, in the right and left eyes, respectively.

Genetic etiology of nuclear cataract: evidence for a major gene.

Sibling correlations and segregation analysis were used to examine the familial distribution of age-sex-adjusted measures of nuclear sclerosis in 1,247 individuals from 564 sibships in the Beaver Dam Eye Study. There are highly significant sibling correlations for all sibs, and separately for sister-sister, sister-brother, and brother-brother pairs. Two transformed normal distributions give the best fit to the data. The hypothesis of mendelian transmission of a major effect cannot be rejected, but the hypothesis of a random environmental major effect is rejected. The parameters of the tau AB free model showed close similarity to the values expected under a mendelian hypothesis. Our results suggest that a single major gene can account for 35% of the total variability of age-sex-adjusted measures of nuclear sclerosis.

The cincinnati myocardial infarction and hormone family study: Family resemblance for dehydroepiandrosterone sulfate in control and myocardial infarction families

Dehydroepiandrosterone sulfate (DHEAS) was examined in random (control) and nonrandom (case) families participating in the Cincinnati Myocardial Infarction and Hormone (CIMIH) family study. The case families were ascertained through white men who survived a myocardial infarction (MI) before the age of 56, whereas control families were recruited through advertisements and through an adolescent boy maturation study. Both familial correlations and genetic effects of DHEAS were investigated. First, maximum likilihood estimates of the sex-specific familial correlations (corrected for nonrandom ascertainment) suggested that there was significant heterogeneity between the two sampling types. This heterogeneity was isolated to the male sibling correlation, which was higher in the case than control families. Post hoc analyses suggested that the sibling group heterogeneity may be in part a function of age, since the control sample offspring were on average much younger than those in case families. No sex differences other than those for the siblings were noted in the familial correlations. Second, heritability was investigated in control families using a simple path model (TAU) that allowed for sex differences. The only significant model parameter was the sex-specific familiality (combined polygenic and familial environmental effects), which was larger in females (74%) than in males (29%). In general, these analyses suggested that (1) DHEAS may play only a limited role in the increased risk for premature MI, and (2) the degree of heritable (familial) variation may be dependent on sex.