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Data from the Medical Birth Registry of Norway were used to estimate sibship correlations in large sibships (each with ≥5 infants among singleton live births surviving the first year of life), while adjusting for covariates such as infant gender, gestational age, maternal age, parity, and time since last pregnancy. This sample of 12,356 full sibs in 2,462 sibships born in Norway between 1968 and 1989 was selected to maximize the information on parity, and a robust approach to estimating both regression coefficients and the sibship correlation using generalized estimating equations (GEE) was employed. In concordance with previous studies, these data showed a high overall correlation in birth weight among full sibs (0.48 ± 0.01), but this sibship correlation was influenced by parity. In particular, the correlation between the firstborn infant and a subsequent infant was slightly lower than between two subsequent sibs (0.44 ± 0.01 vs. 0.50 ± 0.01, respectively). The effect of time between pregnancies was statistically significant, but its predicted impact was modest over the period in which most of these large families were completed. While these data cannot discriminate whether factors influencing birth weight are maternal or fetal in nature, this analysis does illustrate how robust statistical models can be used to estimate sibship correlations while adjusting for covariates in family studies. Genet. Epidemiol. 14:423–433,1997. © 1997 Wiley-Liss, Inc.

In this report we apply methods outlined in the companion paper [Liang, Genet Epidemiol 8:329-338, 1991] to study the association between proband age at onset and familial risk among first-degree relatives of 374 schizophrenic probands. The analyses take into consideration the potential problems of censoring and correlation of age at onset within families. All analyses were done by gender of the proband; age at onset was dichotomized. The results of the analyses of the male probands suggest that there is an increased risk of schizophrenia among the relatives of male probands who have an onset prior to age 17 when compared to relatives of male probands who have an onset later than 16. We did not find an association between age at onset and familial risk among the female probands, but this may be due to the smaller number of female probands and the lower power associated with the analyses.

Markers in five candidate genes were examined on 269 case-parent trios ascertained through a child with an isolated, non-syndromic oral cleft (cleft lip, CL; cleft palate, CP; or cleft lip and palate, CLP). Cases and their parents were ascertained through treatment centers in Maryland. Markers at two of the five candidate genes, transforming growth factor beta3 (TGFbeta3) and MSX1, showed consistent evidence of linkage and disequilibrium due to linkage using several statistical tests (e.g., the global chi-square for TGFbeta3 was 21.1 with 12 df, P = 0.03; that for MSX1 was 8.7 with 3 df, P = 0.03). There was little evidence of heterogeneity in the role of TGFbeta3 between different types of oral clefts, but MSX1 did yield marginal evidence for such heterogeneity. MSX1 also showed evidence for interaction between infant's genotype and maternal smoking, giving a likelihood ratio test for heterogeneity between smoker and non-smoker mothers of 7.16 (2 df, P = 0.03). Using a conditional logistic model to test for gene-gene interaction showed no evidence of interaction between TGFbeta3 and MSX1, with both seeming to contribute independently to risk of isolated, non-syndromic oral clefts.