Using identity-by-de scent information in affected sib pairs to increase the efficiency of genetic association studies

T he aim of this study was to determine whether identity-by-descent (IBD) information for affected sib pairs (ASPs) can be used to select a sample of cases for a genetic case-control study which will provide more power for detecting association with loci in a known linkage region. By modeling the expected frequency of the disease allele in ASPs showing IBD sharing of 0, 1, or 2 alleles, and considering additive, recessive, and dominant disease models, we show that cases selected from IBD 2 families are best for this purpose, followed by those selected from IBD 1 families; least useful are cases selected from IBD 0 families.

Exploring the Etiology of the Association Between Birthweight and IQ in an Adolescent Twin Sample

The negative effects of very low birthweight on intellectual development have been well documented, and more recently this effect has been shown to generalise to birthweights within the normal range. In this study we investigate the etiology of this relationship by using a classical twin design to disentangle the contributions of genes and environment. A previous Dutch study (Boomsma et al., 2001) examining these effects indicated that genes were important in mediating the association of birthweight to full IQ measured at ages 7 and 10, but not at ages 5 and 12. Here the association between birthweight and IQ at age 16 is considered (N = 523 twin pairs). Using variance components modeling we found that the genetic variance in birthweight (4%) completely overlapped with that in verbal IQ but not performance or full IQ. Results further showed the importance of shared environmental effects on birthweight (similar to 60%) but not on IQ (with genes explaining up to 72% of IQ variance). Models incorporating a direction of causation parameter between birthweight and IQ provided adequate fit to the data in either causal direction for performance and full IQ, but the model with verbal 10 causing birthweight was preferred to one in which birthweight influenced verbal IQ. As the measurement of birthweight precedes the measurement of twins' IQ at age 16, the influence of verbal IQ might be better considered as a proxy for parents' 10 or education, and it is possible that brighter mothers provide better prenatal environments for their children.

A comparison of the association between socioeconomic position and cardiovascular disease risk factors in three age cohorts of Australian women: findings from the Australian Longitudinal Study on Women's Health

Objectives To assess the associations between three measurements of socioeconomic position (SEP) - education, occupation and ability to cope on available income - and cardiovascular risk factors in three age cohorts of Australian women. Methods Cross-sectional analysis of three cohorts of Australian women aged 18-23, 45-50 and 70-75 years. Results In general, for all exposures and in all three cohorts, the odds of each adverse risk factor (smoking, obesity and physical inactivity) were lower in the most advantaged compared with the least advantaged. Within each of the three cohorts, the effects of each measurement of SEP on the outcomes were similar. There were, however, some notable between-cohort differences. The most marked differences were those with smoking. For women aged 70-75 (older), those with the highest educational attainment were more likely to have ever smoked than those with the lowest level of attainment. However, for the other two cohorts, this association was reversed, with a stronger association between low levels of education and ever smoking among those aged 18-23 (younger) than those aged 45-50 (mid-age). Similarly, for older women, those in the most skilled occupational classes were most likely to have ever smoked, with opposite findings for mid-age women. Education was also differently associated with physical inactivity across the three cohorts. Older women who were most educated were least likely to be physically inactive, whereas among the younger and mid-age cohorts there was little or no effect of education on physical inactivity. Conclusion These findings demonstrate the dynamic nature of the association between SEP and some health outcomes. Our findings do not appear to confirm previous suggestions that prestige-based measurements of SEP are more strongly associated with health-related behaviours than measurements that reflect material and psychosocial resources.

A genetically informed study of the association between harsh punishment and offspring behavioral problems

Conclusions about the effects of harsh parenting on children have been limited by research designs that cannot control for genetic or shared environmental confounds. The present study used a sample of children of twins and a hierarchical linear modeling statistical approach to analyze the consequences of varying levels of punishment while controlling for many confounding influences. The sample of 887 twin pairs and 2,554 children came from the Australian Twin Registry. Although corporal punishment per se did not have significant associations with negative childhood outcomes, harsher forms of physical punishment did appear to have specific and significant effects. The observed association between harsh physical punishment and negative outcomes in children survived a relatively rigorous test of its causal status, thereby increasing the authors' conviction that harsh physical punishment is a serious risk factor for children.

Dynamic and regulated association of caveolin with lipid bodies: Modulation of lipid body motility and function by a dominant negative mutant

Caveolins are a crucial component of caveolae but have also been localized to the Golgi complex, and, under some experimental conditions, to lipid bodies (LBs). The physiological relevance and dynamics of LB association remain unclear. We now show that endogenous caveolin-1 and caveolin-2 redistribute to LBs in lipid loaded A431 and FRT cells. Association with LBs is regulated and reversible; removal of fatty acids causes caveolin to rapidly leave the lipid body. We also show by subcellular fractionation, light and electron microscopy that during the first hours of liver regeneration, caveolins show a dramatic redistribution from the cell surface to the newly formed LBs. At later stages of the regeneration process (when LBs are still abundant), the levels of caveolins in LBs decrease dramatically. As a model system to study association of caveolins with LBs we have used brefeldin A (BFA). BFA causes rapid redistribution of endogenous caveolins to LBs and this association was reversed upon BFA washout. Finally, we have used a dominant negative LB-associated caveolin mutant (cav(DGV)) to study LB formation and to examine its effect on LB function. We now show that the cav(DGV) mutant inhibits microtubule-dependent LB motility and blocks the reversal of lipid accumulation in LBs.