SEARCH · PubMed Health

Results for “threshold model”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources

PubMed1994

Long-term glycemic control has a nonlinear association to the frequency of background retinopathy in adolescents with diabetes. Follow-up of the Berlin Retinopathy Study.

OBJECTIVE: To assess the influence of long-term glycemic control on the development of background retinopathy in adolescents followed longitudinally from the onset of insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Repeated retinal fluorescein angiographies, in intervals of 1-2 years, were evaluated prospectively in 346 patients (190 males, 156 females; 19.8 [8.8-35.4] years of age; diabetes duration of 10.4 [1.1-27.4] years at their latest eye examination, median [range]). The influences of long-term HbA1c (mean of 18 [1-95] determinations per person) and microalbuminuria (> or = 2 of > or = 3 measurements > or = 15 micrograms/min x 1.73 m2) were studied by multiple linear regression, life-table analysis, and trend analyses. RESULTS: The rate of background retinopathy per 100 patient-years increased with poorer glycemic control from 0.7 (long-term HbA1c < 7% to 7.3 (HbA1c > 11%) following an exponential function. Life-table analysis after subdivision in HbA1c quartiles of equal sizes (HbA1c < 8, 8-9, 9-10, and > 10%) revealed an individual median expectation of background retinopathy after more than 25, 16.2, 12.7, or 12.0 years of diabetes, respectively. However, significant differences were found only between 8-9% and 9-10%, calculated either as prevalence, life-table analysis, or relative incidence, thus suggesting that a threshold model may also fit the data. After 12 years of diabetes, < 25% of those patients exhibiting microalbuminuria (n = 18) were expected to be free from retinopathy compared with 81% of those with normoalbuminuria (n = 86). CONCLUSIONS: Two statistical models are appropriate to explain the relationship between glycemic control and risk for background retinopathy: 1) a continuous exponential relationship as described by the DCCT or 2) the presence of a threshold HbA1c level at 9%. Thus, diabetes treatment in children should aim at long-term HbA1c levels < 9.0%, but every progress closer to normal may further reduce the risk.

Adolescent↗

PubMed1995

Comparison of anticonvulsant efficacy of valproate during prolonged treatment with one and three daily doses or continuous ("controlled release") administration in a model of generalized seizures in rats.

Recently, sustained-release (SR) preparations of valproate (VPA) have been developed to minimize or prevent problems associated with plasma level fluctuations during therapy with conventional preparations. In the present experiments, the anticonvulsant activity of VPA was assessed during prolonged treatment with different administration protocols using the intravenous (i.v.) pentylenetetrazol (PTZ)-infusion seizure threshold model in rats. To simulate a controlled-release (CR) preparation, VPA was infused in a constant rate through chronically implanted intrajugular catheters in some of the experiments. In all experiments, the PTZ seizure threshold was repeatedly determined in individual rats with chronically implanted catheters at daily intervals. Injection of saline three times daily in a control group showed that the PTZ seizure threshold was stable throughout the experiment. Acute administration of VPA 200 mg/kg intraperitoneally (i.p.) significantly increased the seizure threshold. During prolonged treatment with three daily doses of 200 mg/kg i.p., anticonvulsant activity markedly increased on the second day of treatment and thereafter compared to the acute effect of VPA, although plasma levels measured at each seizure threshold determination did not differ significantly. This increase in anticonvulsant activity of VPA during prolonged treatment was much less pronounced with one instead of three daily doses. One daily intraperitoneal injection of VPA (200 mg/kg) plus continuous, constant-rate intravenous infusion of 400 mg/kg/day led to a marked increase in anticonvulsant activity similar to that in the experiment with three daily doses, indicating that not the peak levels but the duration of maintenance of active drug concentrations was important for development of enhanced anticonvulsant activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1980

Neuroendocrine dysfunction in genetic subtypes of primary unipolar depression.

Disinhibited activity of the hypothalamic-pituitary-adrenocortical (HPA) neuroendocrine system, characterized most specifically by abnormal responses to the dexamethasone suppression test (DST), is observed in 40-50% of patients with endogenous depression. The heterogeneity of endogenous depressives with respect to this neuroendocrine marker is so far unexplained. A recent report from Iowa suggested that genetic factors could account for this heterogeneity, since abnormal DST reponses were found with widely differing frequencies among primary unipolar depressives subtyped by the genetic criteria of Winokur. We studied 14 patients with primary endogenous delusional unipolar depression. Abnormal DST responses were found in 79% of the entire group, and with similar frequencies among each of the Winokur subtypes. In particular, five of six patients (83%) with depression spectrum disease had abnormal DST results. This contrasts with a frequency of 4% reported by the Iowa group. We conclude that disinhibited HPA activity does occur in depression spectrum disease when a delusional endogenous depression is present. Our results and those of the Iowa study could both be consistent with a threshold model of HPA activation. The high frequency of positive DST results in delusional endogenous depressives may be determined by disinhibited central pain mechanisms. Variations in this clinical dimension, combined with variations in threshold for HPA activation by pain mechanisms, could account for the heterogeneity of DST responses among endogenous depressives.

Delusions↗

PubMed1993

Panic disorder in women: a population-based twin study.

Previous studies based on probands from clinical samples suggest that panic disorder aggregates strongly in families and may be due to a highly penetrant single major locus. In this study we examine panic disorder as assessed at blind, structured psychiatric interview in 2163 women from a population-based twin registry. DSM-III-R diagnoses were assigned at a narrow and at a broad level both by clinician review and by computer algorithm. The familial aggregation of panic disorder in this sample was only modest. The relatively small number of affected individuals prevented a definitive resolution of competing genetic and non-genetic models of familial transmission. Although there was some inconsistency across diagnostic approaches, most results suggested that the familial aggregation of panic disorder was due largely to genetic factors. Using a multifactorial-threshold model, the best estimates of the heritability of liability ranged from 30 to 40%. From a familial perspective, panic disorder with phobic avoidance appears to represent a more severe form of the syndrome than panic disorder without avoidance. Our results, which suggest that in the general population panic disorder is only a moderately heritable condition, are at variance with results from several previous investigations based on clinically ascertained samples.

Adult↗

PubMed2002

Mathematical models of HIV pathogenesis and treatment.

We review mathematical models of HIV dynamics, disease progression, and therapy. We start by introducing a basic model of virus infection and demonstrate how it was used to study HIV dynamics and to measure crucial parameters that lead to a new understanding of the disease process. We discuss the diversity threshold model as an example of the general principle that virus evolution can drive disease progression and the destruction of the immune system. Finally, we show how mathematical models can be used to understand correlates of long-term immunological control of HIV, and to design therapy regimes that convert a progressing patient into a state of long-term non-progression.

Algorithms↗

PubMed1997

Quantitative risk assessment for a glass fiber insulation product.

California Proposition 65 (Prop65) provides a mechanism by which the manufacturer may perform a quantitative risk assessment to be used in determining the need for cancer warning labels. This paper presents a risk assessment under this regulation for professional and do-it-yourself insulation installers. It determines the level of insulation glass fiber exposure (specifically Owens Corning's R-25 PinkPlus with Miraflex) that, assuming a working lifetime exposure, poses no significant cancer risk under Prop65's regulations. "No significant risk" is defined under Prop65 as a lifetime risk of no more than one additional cancer case per 100,000 exposed persons, and nonsignificant exposure is defined as a working lifetime exposure associated with "no significant risk." This determination can be carried out despite the fact that the relevant underlying studies (i.e., chronic inhalation bioassays) of comparable glass wool fibers do not show tumorigenic activity. Nonsignificant exposures are estimated from (1) the most recent RCC chronic inhalation bioassay of nondurable fiberglass in rats; (2) intraperitoneal fiberglass injection studies in rats; (3) a distributional, decision analysis approach applied to four chronic inhalation rat bioassays of conventional fiberglass; (4) an extrapolation from the RCC chronic rat inhalation bioassay of durable refractory ceramic fibers; and (5) an extrapolation from the IOM chronic rat inhalation bioassay of durable E glass microfibers. When the EPA linear nonthreshold model is used, central estimates of nonsignificant exposure range from 0.36 fibers/cc (for the RCC chronic inhalation bioassay of fiberglass) through 21 fibers/cc (for the i.p. fiberglass injection studies). Lower 95% confidence bounds on these estimates vary from 0.17 fibers/cc through 13 fibers/cc. Estimates derived from the distributional approach or from applying the EPA linear nonthreshold model to chronic bioassays of durable fibers such as refractory ceramic fiber or E glass microfibers are intermediate to the other approaches. Estimates based on the Weibull 1.5-hit nonthreshold and 2-hit threshold models exceed by at least a factor of 10 the corresponding EPA linear nonthreshold estimates. The lowest nonsignificant exposures derived in this assessment are at least a factor of two higher than field exposures measured for professionals installing the R-25 fiberglass insulation product and are orders of magnitude higher than the estimated lifetime exposures for do-it-yourselfers.

Animals↗

PubMed2000

Paternal investment and the human mating system.

Paternal investment has long been considered responsible for the evolution of predominantly monogamous marriage in humans. However, male-male competition resulting in mate-guarding and male coercion could be equally important. In this review, I use a comparative approach to examine the effect of variation in human paternal investment on our mating system. I conclude paternal investment is important but so too is mate-guarding. I propose a model of our mating system incorporating both factors. Variation in the mating system is explained by variation in male resource control and contribution, resulting in ecologically imposed monogamy or polygyny, as predicted by the polygyny threshold model, as well as variation in male-male competition for status, resulting in socially imposed monogamy or polygyny.

Journal Article↗

PubMed2000

Bayesian mapping of quantitative trait loci under the identity-by-descent-based variance component model.

Variance component analysis of quantitative trait loci (QTL) is an important strategy of genetic mapping for complex traits in humans. The method is robust because it can handle an arbitrary number of alleles with arbitrary modes of gene actions. The variance component method is usually implemented using the proportion of alleles with identity-by-descent (IBD) shared by relatives. As a result, information about marker linkage phases in the parents is not required. The method has been studied extensively under either the maximum-likelihood framework or the sib-pair regression paradigm. However, virtually all investigations are limited to normally distributed traits under a single QTL model. In this study, we develop a Bayes method to map multiple QTL. We also extend the Bayesian mapping procedure to identify QTL responsible for the variation of complex binary diseases in humans under a threshold model. The method can also treat the number of QTL as a parameter and infer its posterior distribution. We use the reversible jump Markov chain Monte Carlo method to infer the posterior distributions of parameters of interest. The Bayesian mapping procedure ends with an estimation of the joint posterior distribution of the number of QTL and the locations and variances of the identified QTL. Utilities of the method are demonstrated using a simulated population consisting of multiple full-sib families.

Alleles↗

PubMed2006

Extended LATER model can account for trial-by-trial variability of both pre- and post-processes.

We present a new decision-making model that can account for trial-by-trial variability induced by a process ("pre-process") that occurs before an explicit sensory signal specifying a later motor response. A process after explicit sensory signals, referred to herein as the "post-process", has been investigated by a variety of so-called rise-to-threshold models including the LATER model. The LATER model formulates post-process variability but treats the pre-process as fixed within a block of an experiment. We propose an extension of the LATER model, which we call the extended LATER (ELATER) model, to account for trial-by-trial variability of both pre- and post-processes together. We present the mathematical formulation of the ELATER model and analyze its characteristics, including numerical examples and an example of saccade latency data in reward-manipulated conditions with caudate activity. The ELATER model is useful for investigating decision making by taking account of trial-by-trial variability of both pre- and post-processes.

Animals↗

PubMed2001

Dendritic cells in autoimmune diseases.

Subclinical autoimmune responses can be frequently detected in healthy individuals. Sustained activation of autoreactive lymphocytes is, however, required for the development of autoimmune diseases associated with ongoing tissue destruction either in single organs or generalized with multiple manifestations. Clinical and experimental evidence suggests that prolonged presentation of self antigens by dendritic cells is crucial for the development of destructive autoimmune disease. We discuss here a simplified threshold model where the key parameters for the magnitude of the autoimmune response are the amount of previously ignored self peptides presented by dendritic cells and the duration of the antigen presentation in secondary lymphoid organs. Multiple factors influence the threshold for the conversion of an autoimmune response to overt autoimmune disease. Frequent or persistent viral infections of the target organ may favor autoimmune disease by increasing the amounts of released self antigens, generating cytokine-mediated bystander activation of self-reactive lymphocytes and/or sustaining a chronic response via neoformation of lymphoid structures in the target organ.

Animals↗

PubMed2003

Implementation of a sire-maternal grandsire model for evaluation of calving ease in the United States.

The objective of this study was to add a maternal grandsire (MGS) effect to the existing sire model for national calving ease genetic evaluations. The Animal Improvement Programs Laboratory (AIPL) of USDA assumed responsibility for conducting the national genetic evaluation for calving ease and maintaining the associated database in 1999. Existing evaluations used a sire threshold model. Adding an MGS effect to the model was expected to improve accuracy by partially accounting for merit of mates and differences in maternal ability of the dams. Dystocia data were migrated to a relational database integrated with the AIPL production database. This database design allowed more rigorous data edits by comparison with the production data and improved MGS identification (ID) rate by utilizing pedigrees from the production records. Integration of dystocia data with production data increased MGS ID rate from 58 to 73%. In addition, nearly 200,000 duplicate records were identified using the new edit system. Sire and sire-MGS models were compared using over 10 million observations available for the August 2002 national genetic evaluation. The sire model included herd-year, season, sex of calf, parity of dam, birth year group of sire, and sire. For the sire-MGS model, MGS and birth year group of MGS were added, year-seasons rather than seasons were used, and sex of calf and parity of dam were combined into a single interaction effect. Herd-year, sire, and MGS were random effects. Variance components used for the sire model were those previously used in the national evaluation and for the sire-MGS model were estimated in a separate study. Correlations between predicted genetic merits for service sire calving ease from the two models was 85%, indicating general agreement, but with some significant differences in evaluations. A sire-MGS model was implemented in August 2002 for the national calving ease genetic evaluation system.

Animals↗

PubMed2005

Methodology of mapping quantitative trait loci for ordinal traits of disease resistance in livestock.

Methodology of QTL mapping for ordinal traits of disease resistance based on the framework of a generalized linear model (GLM) was presented. The location and effect parameters of putative QTL were estimated using maximum likelihood method. The efficiency and power were compared with the linear model (LM). The factors influencing QTL detection efficiency (e.g. QTL effect and heritability) were simulated in our study too. Daughter design with multiple families was applied,and the number of segregating population was 500. Results showed that the threshold model has a certain advantage in location estimation and power of QTL mapping, and has efficiency and accuracy for ordinal traits. In addition,the accuracy of QTL mapping depends on the effect of putative quantitative trait loci and the value of heritability. With the increase of QTL effect and heritability, the accuracy of QTL mapping improves slightly.

Animals↗

PubMed2005

Encoding of virtual acoustic space stimuli by neurons in ferret primary auditory cortex.

Recent studies from our laboratory have indicated that the spatial response fields (SRFs) of neurons in the ferret primary auditory cortex (A1) with best frequencies > or =4 kHz may arise from a largely linear processing of binaural level and spectral localization cues. Here we extend this analysis to investigate how well the linear model can predict the SRFs of neurons with different binaural response properties and the manner in which SRFs change with increases in sound level. We also consider whether temporal features of the response (e.g., response latency) vary with sound direction and whether such variations can be explained by linear processing. In keeping with previous studies, we show that A1 SRFs, which we measured with individualized virtual acoustic space stimuli, expand and shift in direction with increasing sound level. We found that these changes are, in most cases, in good agreement with predictions from a linear threshold model. However, changes in spatial tuning with increasing sound level were generally less well predicted for neurons whose binaural frequency-time receptive field (FTRF) exhibited strong excitatory inputs from both ears than for those in which the binaural FTRF revealed either a predominantly inhibitory effect or no clear contribution from the ipsilateral ear. Finally, we found (in agreement with other authors) that many A1 neurons exhibit systematic response latency shifts as a function of sound-source direction, although these temporal details could usually not be predicted from the neuron's binaural FTRF.

Acoustic Stimulation↗

PubMed1997

Stage duration and increase of work load in incremental testing on a cycle ergometer.

Any variation of the test protocol for incremental testing (IT) in cycle ergometry may affect the accuracy of the determination of anaerobic threshold (AnT). For lactate threshold concepts, indicating the maximum lactate steady-state (max Lass), the formation of the quasi-steady-state (QSS=95% of steady-state level) is evident. Previous studies have not specified the time that it takes for blood lactate to stabilize following incremental changes in WL. The purpose of this study was to identify the minimum duration of exercise necessary to establish QSS following various increments in WL (10, 20, 30, 40 and 50 W). Eight male endurance-trained cyclists [relative maximal oxygen consumption = 64.8 (4.2) ml x kg(-1) x min(-1)] performed three different exercise tests on a cycle ergometer: (1) an exhaustive IT with a starting WL of 100 W, followed by 20-W increments every 3 min; (2) a threshold test with 20-W increments every 9 min to determine the MaxLaSS; and (3) five incremental exercise tests (from 100/110 W, with 20-W increments every 3 min) with a final 10-, 20-, 30-, 40- or 50- W increment lasting 10 min, at 10 W below MaxLaSS (T10-T50 experiments). The time constant of lactate kinetics (tau), the time constant of lactate elimination, and the time taken to elicite QSS, defined as 95% of the time taken to reach steady-state level (t95%), were calculated in the T10-T50 experiments. The tau and t95% increased significantly with WL increment size: the correlation was not linear. Smaller WL increments required proportionally longer durations. Mean (SD) t95% values (min:s) were 1:57 (0:27) (T10), 2:58 (0.16) (T20), 4:08 (0:23) (T30), 4:45 (0:45) (T40) and 5:06 (0:43) (T50). The application of these references in IT protocols may lead to an extension of total test duration, particularly with smaller increments. Therefore, lactate threshold modelling, the training status of the athletes and comparability with lactate measurements obtained during training events should be considered. IT protocols not accomplishing QSS criteria may effect an underestimation of WL-related lactate values and an overestimation of lactate thresholds, which indicate MaxLaSS, especially in highly trained athletes. This suggests that the establishment of an increment-size-dependent t95% may reduce protocol-related influences on AnT and standardize the use of the AnT in IT procedures in the training management of elite cyclists.

Adult↗

PubMed1993

Autoinduction of nuclear receptor genes and its significance.

Although downregulation of receptors by their respective hormonal ligands is a well-studied phenomenon, relatively less is known about autoupregulation of receptors. However, an increasing number of observations of the latter process are now being reported. Here, we discuss the phenomenon of autoinduction of nuclear receptors of the steroid/thyroid hormone gene family, and its significance in the context of the developmental and gene regulatory function of the ligands. Much of this review is illustrated by recent work from our laboratory on the autoregulation of Xenopus estrogen (ER) and thyroid hormone (TR) receptors and their transcripts, accompanying or anticipating vitellogenesis and metamorphosis, respectively. The activation by estrogen (E2) of the silent vitellogenin genes and the induction of FOSP-1 genes in primary cultures of hepatocytes from male Xenopus and oviduct cells, respectively, are tightly coupled to a substantial upregulation of ER protein and its transcript. The developmental competence to activate vitellogenin in response to E2 was found to be acquired during late metamorphosis. Since the latter process is obligatorily controlled by thyroid hormones (TH), we extended our studies to the developmental and hormonal regulation of Xenopus TR genes. Although very low levels of TR alpha and beta mRNAs are detectable in embryos and early larvae, there is a large increase in the accumulation of both transcripts before the onset of metamorphosis (stage 54 tadpoles), by which time the larval thyroid gland has first begun to secrete TH. Filter and in situ hybridization revealed that the two transcripts were differentially regulated and were not equally distributed in all regions or tissues of the tadpole. Their concentration peaks at metamorphic climax and drops to low levels in froglets and adult Xenopus. Exogenous TH given to pre-metamorphic tadpoles is known to induce metamorphosis precociously. Administration of triiodothyronine (T3) to early tadpoles (stages 50/52) caused a rapid upregulation of TR alpha and beta mRNAs which was particularly marked for the beta transcript (20- to 50-fold increase in steady-state levels). This autoinduction, which is the earliest response to T3, is mimicked to variable degrees in some Xenopus cell lines. In XTC-2 cells, in which the in vivo process is fully reproduced, it was possible to show with cycloheximide that the increase in TR mRNA requires protein synthesis. It was also possible to show by transfection of XTC-2 cells with a reporter-promoter construct of Xenopus albumin gene, which is a target for T3, that the extra TR mRNA increases functional receptor in the cell. Although the role of TH is well-known in metamorphosis, we found that TR is also autoinduced in primary culture of adult male Xenopus hepatocytes. The significance of this finding lies in the fact that T3 potentiates the autoinduction of ER and the de novo activation of vitellogenin genes by E2. Prolactin (PRL) is known to exert a "juvenilizing" action by preventing the induction of amphibian metamorphosis by TH. It is therefore highly significant that PRL prevented both the autoinduction of TR alpha and beta mRNAs in whole tadpoles and organ cultures and the activation of TR target genes, such as those encoding albumin and 63 kDa adult-type keratin. Although how PRL exerts its antimetamorphic effect is not known, these findings lead us to propose a dual threshold model for the autoinduction of TR, whereby the autoinduction of TR genes requires a very low level of TR and TH to rapidly augment the amount of functional TR. This higher amount of receptor would be required to achieve a higher threshold to activate "downstream" or target genes which specify the adult phenotype at the end of metamorphosis. Finally, a survey of recent literature shows that the phenomenon of autoinduction is not restricted to Xenopus ER and TR but is more widespread among members of the nuclear receptor family.

Animals↗

PubMed2005

Predictive risk thresholds for survival protection of farmed abalone, Haliotis diversicolor supertexta, exposed to waterborne zinc.

Using a probabilistic risk-based framework, we have developed a simple predictive risk threshold model for protecting the survival of farmed abalone, Haliotis diversicolor supertexta, exposed to waterborne zinc (Zn). Probabilistic techniques using Monte Carlo analysis propagate parameter uncertainty/variability throughout the model, providing decision makers with a credible range of information and increased flexibility in establishing a specific Zn level in aquacultural ecosystems. We coupled a first-order two-compartment bioaccumulation model with a reconstructed dose-response profile based on a three-parameter Hill equation model to form a probabilistic risk model in order to determine the risk quotient associated with a 10% probability of exceeding the abalone 5% effect concentration (EC(5)) at site-specific abalone farms. Sensitivity analysis revealed that waterborne Zn concentration (C(w)) and algae bioconcentration factor (BCF(a)) have a significant effect on Zn levels in abalone. Using multiple nonlinear regression analysis with C(w) and BCF(a) as the parameters, a predictive risk threshold equation that can be used in a variety of site-specific conditions was developed for protecting the survival of farmed abalone. We believe this probabilistic framework provides an effective method for conceptualizing a public policy decision vis-a-vis the establishment of a specific acceptable risk threshold for aquacultural water quality management.

Animals↗

PubMed2005

A conceptual framework for performance diagnosis and training prescription from submaximal gas exchange parameters--theory and application.

The first part of this article intends to give an applicable framework for the evaluation of endurance capacity as well as for the derivation of exercise prescription by the use of two gas exchange thresholds: aerobic (AerTGE) and anaerobic (AnTGE). AerT GE corresponds to the first increase in blood lactate during incremental exercise whereas AnTGE approximates the maximal lactate steady state. With very few constraints, they are valid in competitive athletes, sedentary subjects, and patients. In the second part of the paper, the practical application of gas exchange thresholds in cross-sectional and longitudinal studies is described, thereby further validating the 2-threshold model. It is shown that AerTGE and AnTGE can reliably distinguish between different states of endurance capacity and that they can well detect training-induced changes. Factors influencing their relationship to the maximal oxygen uptake are discussed. Finally, some approaches of using gas exchange thresholds for exercise prescription in athletes, healthy subjects, and chronically diseased patients are addressed.

Age Factors↗

PubMed1999

Twin mothers, pregnancy hypertension and pre-eclampsia.

OBJECTIVE: To estimate the maternal genetic contribution to the hypertensive diseases of pregnancy. DESIGN: A cohort study of female twins with information on hypertensive diseases of pregnancy obtained by questionnaire screening, and verification of diagnosis from hospital or general practitioner records. SETTING: A volunteer twin registry in the UK with recruitment through the media without reference to pregnancies or disease status. POPULATION: Adult female, same-sex twin pairs who completed a pregnancy history questionnaire and consented to record inspection. MAIN OUTCOME MEASURE: Self-reported and hospital-validated diagnosis of non-proteinuric pregnancy hypertension and of pregnancy hypertension with proteinuria (pre-eclampsia). RESULTS: Self-reported pre-eclampsia had a heritability of 0.221 and non-proteinuric hypertension of 0. 198. However, none of the pairs who were self-reported as concordant for pre-eclampsia were confirmed from hospital records. Using hospital records, the heritability of pre-eclampsia was 0 and 0.375 for non-proteinuric hypertension. Using a model treating pre-eclampsia as a separate disease from non-proteinuric hypertension, and assuming that the next pair identified was both monozygotic and concordant for pre-eclampsia, the estimated heritability of pre-eclampsia remained 0 (95% CI 0-0.49). Using a threshold model in which non-proteinuric hypertension is treated as a mild form of pre-eclampsia, heritability is estimated at 0.247 (95% CI 0.23-0.454). CONCLUSION: Neither non-proteinuric hypertension nor pre-eclampsia are inherited in simple Mendelian fashion. The genetic contribution to multi-factorial inheritance is smaller than hitherto believed.

Adolescent↗