Reynir Tómas Geirsson

Abstract Endometriosis is a heritable hormone-dependent gynecological disorder, associated with severe pelvic pain and reduced fertility; however, its molecular mechanisms remain largely unknown. Here we perform a meta-analysis of 11 genome-wide association case-control data sets, totalling 17,045 endometriosis cases and 191,596 controls. In addition to replicating previously reported loci, we identify five novel loci significantly associated with endometriosis risk ( P <5 × 10 −8 ), implicating genes involved in sex steroid hormone pathways ( FN1 , CCDC170 , ESR1 , SYNE1 and FSHB ). Conditional analysis identified five secondary association signals, including two at the ESR1 locus, resulting in 19 independent single nucleotide polymorphisms (SNPs) robustly associated with endometriosis, which together explain up to 5.19% of variance in endometriosis. These results highlight novel variants in or near specific genes with important roles in sex steroid hormone signalling and function, and offer unique opportunities for more targeted functional research efforts.

Familial predisposition and patterns of genetic inheritance of eclampsia and pre-eclampsia were investigated through three or four generations in 94 families from the homogenous island population of Iceland. The families descended from index women delivered in the years 1931-47 and who had either eclampsia (n = 38) or severe pre-eclampsia (n = 69). Inheritance was followed both through sons and daughters. The prevalence of pre-eclampsia and eclampsia in daughters was significantly higher (23%) than that in daughters-in-law (10%). No difference was noted in the prevalence of these diseases by whether the daughter was born of an eclamptic or pre-eclamptic mother or whether she was a first or later born daughter. There was a non-significantly higher occurrence of pre-eclampsia among grand-daughters than in grand-daughters-in-law. No difference was seen by whether grand-daughters descended through sons or daughters. With increasing numbers of affected daughters or grand-daughters the probability rose of finding more affected women in a family. Hypotheses of single recessive and dominant gene inheritance were compared and maximum likelihood estimates for gene frequency obtained. For a single recessive gene model this was 0.31 reflecting a population prevalence of 9.6%, whereas a dominant model with incomplete penetrance gave 0.14 at 48% gene penetrance, corresponding to a population prevalence of 0.9% homozygous expression of severe disease and 11% heterozygous expression of milder disease. Either genetic model could fit the data.

BACKGROUND: Evidence about the influence of hypertension in pregnancy on later health and in particular the risk of cardiovascular disorders is conflicting, although a link has been suggested. In a population-based study with a long follow-up time the potential association between hypertension in pregnancy, preeclampsia and eclampsia with increased death rates from ischemic heart disease (IHD) was investigated. METHODS: All 7543 case records at the main maternity hospital in Iceland during 1931-1947 were reviewed to identify women with hypertension in pregnancy, subdivided by parity and severity of disease into those with eclampsia, preeclampsia and hypertension alone. Information on those who had died was obtained from death certificates, supplemented by autopsy reports and hospital records. Death rates from IHD were compared to population data from public health and census reports during corresponding periods and between study groups. RESULTS: Of 374 hypertensive women 177 had died. The death rate was slightly higher among women with any hypertension in pregnancy than in the reference population (RR = 1.20; 95% CI 1.01-1.42). About half of the increase was attributed to excess mortality from IHD with a relative risk of dying of 1.47 (95% CI 1.05-2.02). The relative risk of dying from IHD was significantly higher among eclamptic women (RR = 2.61; 95% CI 1.11-6.12) and those with preeclampsia (RR = 1.90; 95% CI 1.02-3.52) than those with hypertension alone. Parous women at the index pregnancy had a twofold higher risk of dying from IHD than primigravid women (RR = 2.05; 95% CI 1.19-3.55; p = 0.01). CONCLUSION: There is an indication of increased death rates among women with a history of hypertension in pregnancy, where ischemic heart disease may be more common than in the general population.