Genetics of gene expression and its effect on disease.

Common human diseases result from the interplay of many genes and environmental factors. Therefore, a more integrative biology approach is needed to unravel the complexity and causes of such diseases. To elucidate the complexity of common human diseases such as obesity, we have analysed the expression of 23,720 transcripts in large population-based blood and adipose tissue cohorts comprehensively assessed for various phenotypes, including traits related to clinical obesity. In contrast to the blood expression profiles, we observed a marked correlation between gene expression in adipose tissue and obesity-related traits. Genome-wide linkage and association mapping revealed a highly significant genetic component to gene expression traits, including a strong genetic effect of proximal (cis) signals, with 50% of the cis signals overlapping between the two tissues profiled. Here we demonstrate an extensive transcriptional network constructed from the human adipose data that exhibits significant overlap with similar network modules constructed from mouse adipose data. A core network module in humans and mice was identified that is enriched for genes involved in the inflammatory and immune response and has been found to be causally associated to obesity-related traits.

Recurrence of hypertensive disorder in second pregnancy.

OBJECTIVE: The purpose of this study was to investigate the recurrence of hypertensive disorders in pregnancy with regard to the type of disorder, the onset of hypertension, and the modulating effect of overweight and weight gain between pregnancies. STUDY DESIGN: Maternity records from 896 parous women with hypertensive disorders in pregnancy in the first pregnancy were reviewed to reclassify disease status and calculate odds ratios for recurrence. RESULTS: Recurrence of hypertensive disorders in pregnancy occurred in 58% to 94% of second pregnancies, depending on first pregnancy disorder. Overweight (odds ratio, 1.82) and weight gain (odds ratio, 2.20) were related to recurrence among women with gestational hypertension. Early hypertension (

Paternity change and the recurrence risk in familial hypertensive disorder in pregnancy.

OBJECTIVE: To investigate if there is an increased risk for recurrence of hypertensive disorder in pregnancy with a new partner and whether this is affected by maternal age and the interbirth interval through use of familial material. METHODS: Data on 614 multiparous women, with confirmed de novo hypertensive disorder in a first pregnancy, were used to assess the effect of paternity and interbirth interval on recurrence of hypertensive disorders. RESULTS: There were 121 women (19.7%) who had changed partner. Recurrent hypertension occurred in 318 women (64.5%) with the same partner and in 75 women (62%) with a new partner. The odds ratio (OR) for recurrence with the same partner was 1.115 (95% CI 0.739-1.680) and with a new partner 0.897 (95% CI 0.595-1.353). The mean interbirth interval was longer for women with recurrent hypertension (4.9 vs. 4.0 years, p = 0.0002). The OR for developing recurrent hypertensive disorder was 1.154 (95% CI 1.049-1.269) for every interval year with the same partner and 1.145 (95% CI 0.958-1.368) with a new partner after correction for maternal age. CONCLUSION: In women with a positive family history and previous hypertension in pregnancy, change of paternity does not influence the risk of recurrence. Increasing interbirth interval may account for a 15% recurrence risk for each year, independent of maternal age. There was no indication that a change of partner conferred any influence on the recurrence risk that is not explained with birth interval or age.