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In an empirical study on the classification of the psychoses, 302 patients were rated using the Longitudinal Psychopathology Schedule. The data were condensed by factor analysis, which yielded 10 factors - mania and schizomania, depression and suicidal activity, and 6 factors concerned with psychotic symptoms (verbal hallucinosis/passivity, delusion formation, defect symptoms, social decline, cycloid symptomatology and a factor loading depressive auditory hallucinations and visual hallucinations). Provisional diagnostic groups were obtained using DSM III. Discriminant function analyses showed that the only clearly distinct diagnostic group was bipolar disorder, and this was true for various definitions. Canonical variate analyses were performed using 3- and 4-criterion groups. These showed that a group corresponding approximately to cycloid psychosis also met criteria for being a distinct group. The most detailed examination pf the data, using 4-criterion groups and serial reclassification, suggested that the psychoses might fall into 5 groups - bipolar disorder, cycloid psychosis, depression, defect states and schizoaffective depression.
Suicidal behaviour shows evidence of familial clustering and the twin data on completed suicide suggest moderate heritability. The extent to which the genetics of suicidal behaviour overlaps with the genetics of affective disorders is unclear but there is overwhelming evidence that both bipolar and unipolar disorder are substantially influenced by genes. So far, candidate gene studies of suicidality have provoked much interest, but recently, attention has also turned to candidate gene approaches to suicidal ideation emerging during antidepressant treatment. The advent of genome-wide association studies (GWAS) has had a major impact on studies of affective disorder with some provocative new findings. The GWAS approach is also beginning to be applied in the search for genes that underlie suicidal ideation and behaviour.
Depression and obesity are highly prevalent major public health problems that frequently co-occur. Shared aetiological factors have been found between depression and obesity. The role of the fat mass and obesity associated (FTO) gene in body mass index (BMI) and obesity has been confirmed in many independent studies. Recently, we reported the first study implicating FTO in the association between depression and obesity.
We aimed to confirm these findings by investigating the FTO rs9939609 polymorphism in a meta-analysis of 13,701 individuals.
The sample consists of 6,902 depressed cases and 6,799 controls from five studies (Radiant, PsyCoLaus, GSK, MARS and NESDA/NTR). Common inclusion criteria were information available on a lifetime DSM-IV diagnosis of major depressive disorder (MDD), BMI and genotype data. Linear regression models for quantitative traits assuming an additive genetic model were performed to test for association and interaction between rs9939609, BMI and depression. Fixed and random-effects meta-analyses were performed.
Fixed-effects meta-analyses support a significant association between rs9939609 polymorphism and BMI (whole-sample: ß=0.07, p=1.29×10-12, depressive-cases: ß=0.12, p=6.92×10-12). No association was found in controls (ß=0.02, p=0.15). Meta-analyses further support a significant interaction between FTO, BMI and depression (fixed-effects: ß=0.13, p=3.087×10-7; random-effects: ß=0.12, p=0.027), wherein depressed carriers of the risk allele have an additional increase of 2.2% in BMI.
This meta-analysis demonstrates a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. Depression-related alterations in key biological processes may interact with the rs9939609 FTO risk allele to increase obesity risk.
Mammary development takes place during the growing and gestation periods in swine but it also continues after farrowing. In fact, a significant proportion of mammary accretion occurs during lactation and is stimulated by suckling. After piglets are weaned, there is involution of the mammary glands and the process of mammogenesis starts again during the next parity. Suckling of a teat for the first 12 to 14 h after farrowing is not sufficient to maintain lactation, and mammary involution accompanied by alterations in gene transcription will take place. The involution process is reversible within 1 day postpartum but is not reversible if a mammary gland is unsuckled for 3 days. Mammary glands that undergo involution early in lactation do not show further involution in the post-weaning period. The action of a teat being suckled does not only affect mammary development in the ongoing lactation but it also impacts mammogenesis in the following lactation. Indeed, when a mammary gland is not suckled in first parity it has a diminished development and lower milk yield in second parity. Furthermore, it was shown that suckling of a teat for only the first 2 days postpartum in primiparous sows is sufficient to ensure optimal mammary development and milk yield from that teat in the next lactation. The behavior of nursing piglets in early lactation is also affected by whether or not a teat was previously used. Such knowledge on lactation biology is essential in order to develop the best adapted management strategies for the currently used hyperprolific sow lines and to optimize growth rate of their piglets. This review gives an update on the role of suckling for mammary development in lactating sows and on how it can affect management strategies of primiparous sows.
Colostrum plays an essential role in ensuring the survival, growth and health of piglets by providing energy, nutrients, immunoglobulins, growth factors and many other bioactive components and cells. Both colostrum yield and composition are highly variable among sows, yet mechanisms and factors that regulate colostrogenesis are not fully known. Unlike sow milk yield, sow colostrum yield is not highly determined by litter size and suckling intensity but is largely driven by sow-related factors. Colostrum synthesis is under hormonal control, with prolactin and progesterone concentrations prepartum having, respectively, positive and negative influences on colostrum yield. Less is known about the endocrine control of the end of colostrogenesis in swine, which is characterized by the closure of tight junctions in the mammary epithelium and the cessation of transfer of immunoglobulin G (IgG) into lacteal secretions. Recent studies indicate that exogenous hormones may influence colostrogenesis. Inducing parturition by injecting prostaglandin F2α on day 114 of gestation in combination with an oxytocin-like molecule reduced colostrum yield, and injection of prostaglandin F2α alone either reduced colostrum yield or had no effect. Injecting a supraphysiological dose of oxytocin to sows in the early postpartum period delayed the tightening of mammary tight junctions, thereby prolonging the colostral phase and increasing concentrations of IGF-I and IgG and IgA in early milk. The development of strategies to improve colostrum composition in swine through maternal feeding has been largely explored but very few attempts were made to increase colostrum yield. This is most likely because of the difficulty in measuring colostrum yield in swine. The fatty acid content of colostrum greatly depends on the amount of lipids provided in the sow diet during late gestation, whereas the fatty acid profile is largely influenced by the type of lipid being fed to the pregnant sow. Moreover, various ingredients that presumably have immuno-modulating effects (such as fish oil, prebiotics and probiotics) increased concentrations of IgG, IgA and/or IgM in sow colostrum when they were provided during the last weeks of gestation. Finally, there is some evidence that sow nutrition during late gestation may influence colostrum yield but this clearly warrants more research. This review emphasizes that although progress has been made in understanding the control of colostrogenesis in swine, and that strategies exist to manipulate fat and immunoglobulin contents of colostrum, ways to increase colostrum yield are still lacking.
Background: Focal cortical dysplasias (FCDs) are congenital structural abnormalities of the brain, and represent the most common cause of medication-resistant focal epilepsy in children and adults. Recent studies have shown that somatic mutations (i.e. mutations arising in the embryo) in mTOR pathway genes underlie some FCD cases. Specific therapies targeting the mTOR pathway are available. However, testing for somatic mTOR pathway mutations in FCD tissue is not performed on a clinical basis, and the contribution of such mutations to the pathogenesis of FCD remains unknown. Aim: To investigate the feasibility of screening for somatic mutations in resected FCD tissue and determine the proportion and spatial distribution of FCDs which are due to low-level somatic mTOR pathway mutations. Methods: We performed ultra-deep sequencing of 13 mTOR pathway genes using a custom HaloPlexHS target enrichment kit (Agilent Technologies) in 16 resected histologically-confirmed FCD specimens. Results: We identified causal variants in 62.5% (10/16) of patients at an alternate allele frequency of 0.75–33.7%. The spatial mutation frequency correlated with the FCD lesion’s size and severity. Conclusions: Screening FCD tissue using a custom panel results in a high yield, and should be considered clinically given the important potential implications regarding surgical resection, medical management and genetic counselling.
To achieve their conservation goals individuals, communities and organizations need to acquire a diversity of skills, knowledge and information (i.e. capacity). Despite current efforts to build and maintain appropriate levels of conservation capacity, it has been recognized that there will need to be a significant scaling-up of these activities in sub-Saharan Africa. This is because of the rapid increase in the number and extent of environmental problems in the region. We present a range of socio-economic contexts relevant to four key areas of African conservation capacity building: protected area management, community engagement, effective leadership, and professional e-learning. Under these core themes, 39 specific recommendations are presented. These were derived from multi-stakeholder workshop discussions at an international conference held in Nairobi, Kenya, in 2015. At the meeting 185 delegates (practitioners, scientists, community groups and government agencies) represented 105 organizations from 24 African nations and eight non-African nations. The 39 recommendations constituted six broad types of suggested action: (1) the development of new methods, (2) the provision of capacity building resources (e.g. information or data), (3) the communication of ideas or examples of successful initiatives, (4) the implementation of new research or gap analyses, (5) the establishment of new structures within and between organizations, and (6) the development of new partnerships. A number of cross-cutting issues also emerged from the discussions: the need for a greater sense of urgency in developing capacity building activities; the need to develop novel capacity building methodologies; and the need to move away from one-size-fits-all approaches.
The chemical composition of soil from the Glasgow (UK) urban area was used to identify the controls on the availability of potentially harmful elements (PHEs) in soil to humans. Total and bioaccessible concentrations of arsenic (As), chromium (Cr) and lead (Pb) in 27 soil samples, collected from different land uses, were coupled to information on their solid-phase partitioning derived from sequential extraction data. The total element concentrations in the soils were in the range <0.1–135mgkg–1 for As; 65–3680mgkg–1 for Cr and 126–2160mgkg–1 for Pb, with bioaccessible concentrations averaging 27, 5 and 27% of the total values, respectively. Land use does not appear to be a predictor of contamination; however, the history of the contamination is critically important. The Chemometric Identification of Substrates and Element Distribution (CISED) sequential chemical extraction and associated self-modelling mixture resolution analysis identified three sample groupings and 16 geochemically distinct phases (substrates). These were related to iron (n=3), aluminium–silicon (Al–Si; n=2), calcium (n=3), phosphorus (n=1), magnesium (Mg; n=3), manganese (n=1) and easily extractable (n=3), which was predominantly made up of sodium and sulphur. As, Cr and Pb were respectively found in 9, 10 and 12 of the identified phases, with bioaccessible As predominantly associated with easily extractable phases, bioaccessible Cr with the Mg-dominated phases and bioaccessible Pb with both the Mg-dominated and Al–Si phases. Using a combination of the Unified Barge Method to measure the bioaccessibility of PHEs and CISED to identify the geochemical sources has allowed a much better understanding of the complexity of PHE mobility in the Glasgow urban environment. This approach can be applied to other urban environments and cases of soil contamination, and made part of land-use planning.
Silymarin is an extract from the plant milk thistle that was shown to have antioxidant and hyperprolactinemic properties. Taking into account the essential role of prolactin for lactating sows and the systemic oxidative stress occurring during lactation, it is of interest to investigate the potential beneficial effects of silymarin on lactating sows. A study was therefore carried out to determine the effects of providing either 1 or 8 g/day of the plant extract silymarin to lactating sows. Sows in first, second or third parity were fed conventional diets during gestation and, at farrowing, were assigned as controls (CTL, n=33), or were fed 1 g/day (SYL1, n=33) or 8 g/day (SYL8, n=33) of silymarin. The silymarin was provided in two equal amounts per day, and was fed throughout a 20-day lactation. The performance of sows and their litters was assessed and circulating concentrations of prolactin (days 7 and 18), urea (days 7 and 18) and oxidative status, via protein carbonyls and superoxide dismutase activity (day 18), were measured in sows. Milk samples were obtained on day 18 to measure standard composition. There was no effect of silymarin (P>0.10) on circulating prolactin or urea, or on oxidative damage to proteins or antioxidant potential in sows. Lactation feed intake, backfat and BW of sows were unaffected by treatment (P>0.10) as was the case for milk composition and piglet growth (P>0.10). Results demonstrate that providing up to 8 g/day of the plant extract silymarin to lactating sows had no beneficial effects in terms of circulating prolactin concentrations or oxidative status of sows, or in terms of performances of sows and their litters.
Due to their functional similarity to estradiol, phytoestrogens could prove to be beneficial in late gestating sows. The goal of this study was to determine the impact of providing the phytoestrogen genistein during late pregnancy on the performance of sows and their litters. In total, 56 gilts were equally divided into the two following groups on day 90 of gestation: (1) controls (CTL); and (2) two daily i.m. injections of 220 mg of genistein (GEN). Treatments were carried out until farrowing. Jugular blood samples were collected from 16 gilts/treatment on days 89 and 110 of gestation, and on days 3 and 21 of lactation. Milk samples were also obtained from those sows on day 3 of lactation. A male piglet from 16 CTL and 15 GEN litters was slaughtered at 24 h postpartum and a blood sample was obtained. The liver, heart and visceral organs were weighed and the semitendinosus (ST) muscle was collected and carcass composition was determined. The treatment increased (P<0.05) the concentrations of genistein and daidzein in the plasma of gilts on day 110 of gestation and of genistein in the plasma of piglets at 24 h postpartum. It also increased IGF1 concentrations in gilts at the end of the treatment period (P<0.05). Genistein had no impact (P>0.1) on weight or backfat loss of sows during lactation, milk composition or weights of piglets. The pre-weaning mortality rate of piglets was very low (<7%), yet the odds ratio comparing CTL with GEN sows indicated almost twice as many chances of pre-weaning deaths occurring in litters from CTL than GEN sows. Weights of the piglet carcasses were similar for both treatments, as well as weights of the various organs and of the ST muscle (P>0.1). However, carcasses from GEN litters contained more fat than those from CTL litters (9.63% v. 8.34%, P<0.05). None of the biochemical properties of the ST muscle differed between groups (P>0.1). In conclusion, injecting gilts with 440 mg/day of genistein in late gestation increased IGF1 concentrations in gilts and carcass fat in neonatal piglets, but had minimal effect on muscle development of piglets at birth and on the performance of lactating sows and their litters.
Major depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene–environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD.
The RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them.
PRS significantly predicted depression, explaining 1.1% of variance in phenotype (p = 1.9 × 10−6). SLEs and CT were also associated with MDD status (p = 2.19 × 10−4 and p = 5.12 × 10−20, respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p = 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples.
CT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene–environment interactions in complex traits.
Intrauterine variations in nutrient allowance can alter body composition and tissue features of the porcine offspring around birth. This study aimed to determine the effects of fetal weight variations between littermates and of maternal dietary regimen during gestation on fetal muscle traits just before birth. Fourteen pregnant gilts were reared under a conventional (control, CTL; n=7) or an experimental (treatment, TRT; n=7) dietary regimen during gestation. The dietary treatment provided 70% of the protein and digestible energy contents of the CTL diet during the first 70 days of gestation and then, 115% of the protein and digestible energy contents up to farrowing. At 110 days of gestation, sows were sacrificed and one fetus having a low (824±140 g) and one having a normal (1218±192 g) BW per litter were sampled. Irrespective of maternal dietary regimen, the longissimus muscle of the small fetuses exhibited higher expression levels of DLK1/Pref1 and NCAM1/CD56, two genes known to be downregulated during normal skeletal muscle development. Expression levels of the embryonic isoform of the myosin heavy chain (MyHC), both at the mRNA and at the protein levels, were also higher in small fetuses. In addition, the ratios of perinatal to embryonic and of adult fast to developmental MyHC isoforms were generally lower in light fetuses compared with their medium-weight littermates. These modifications suggest a delayed myofiber development in spontaneous growth-retarded fetuses. Finally, GLUT1 was expressed to a lesser extent in the muscle of small v. normal fetuses, suggesting decreased ability for glucose uptake in muscle. Initial feed restriction and subsequent overfeeding of sows during gestation led to a lower expression of the myogenic factor MYOD1, a prerequisite for myogenic initiation in skeletal muscle. This maternal strategy was also associated with a lower expression level of insulin-like growth factor 1 receptor (IGFR) but an upregulation of IGF2. This suggests an altered susceptibility of muscle cells to IGFs’ signal in fetuses from treated sows. Altogether, intrauterine growth restriction impaired fetal muscle development, and restricted feeding followed by overfeeding of gestating sows did not allow small fetuses to recover normal contractile and metabolic characteristics.
Background: Febrile infection-related epilepsy syndrome (FIRES) is a devastating entity characterized by acute onset of refractory epileptic status preceded by a febrile infection, for which no aetiology has been identified so far. Methods: We report the cases of two males presenting with typical FIRES, for whom extensive investigations revealed no specific aetiology. Failure of controlling seizures with multiple anticonvulsants as well as barbiturate coma lead to the decision to try immunotherapy. The first patient received plasma exchange after a negative trial of IVIGs, while the second received plasma exchange in the beginning. Results: Significant improvement in the seizure frequency and intensity was obtained following plasma exchange, and weaning of barbiturate coma was successful in the days following treatment. Both patients remain with significant temporal lobe epilepsy, requiring treatment with 3 anti epileptics. However, cognitive outcome is surprisingly good for both, both exhibiting normal IQs and normal everyday function, with the second patient showing even better recovery, possibly due to earlier treatment with plasma exchange. Conclusion: Our findings of favourable outcome with plasma exchange favours the auto-immune hypothesis often discussed in FIRES. While awaiting further insight onto the aetiology of this syndrome, we suggest a trial of plasma exchange in patients affected.
Strategies to dissect phenotypic and genetic heterogeneity of major depressive disorder (MDD) have mainly relied on subphenotypes, such as age at onset (AAO) and recurrence/episodicity. Yet, evidence on whether these subphenotypes are familial or heritable is scarce. The aims of this study are to investigate the familiality of AAO and episode frequency in MDD and to assess the proportion of their variance explained by common single nucleotide polymorphisms (SNP heritability).
For investigating familiality, we used 691 families with 2–5 full siblings with recurrent MDD from the DeNt study. We fitted (square root) AAO and episode count in a linear and a negative binomial mixed model, respectively, with family as random effect and adjusting for sex, age and center. The strength of familiality was assessed with intraclass correlation coefficients (ICC). For estimating SNP heritabilities, we used 3468 unrelated MDD cases from the RADIANT and GSK Munich studies. After similarly adjusting for covariates, derived residuals were used with the GREML method in GCTA (genome-wide complex trait analysis) software.
Significant familial clustering was found for both AAO (ICC = 0.28) and episodicity (ICC = 0.07). We calculated from respective ICC estimates the maximal additive heritability of AAO (0.56) and episodicity (0.15). SNP heritability of AAO was 0.17 (p = 0.04); analysis was underpowered for calculating SNP heritability of episodicity.
AAO and episodicity aggregate in families to a moderate and small degree, respectively. AAO is under stronger additive genetic control than episodicity. Larger samples are needed to calculate the SNP heritability of episodicity. The described statistical framework could be useful in future analyses.
We address the problem of evaluating an
-function when only a small number of its Dirichlet coefficients are known. We use the approximate functional equation in a new way and find that it is possible to evaluate the
-function more precisely than one would expect from the standard approach. The method, however, requires considerably more computational effort to achieve a given accuracy than would be needed if more Dirichlet coefficients were available.
Despite its importance as a public health concern, relatively little is known about the natural course of cannabis use disorders (CUDs). The primary objective of this research was to provide descriptive data on the onset, recovery and recurrence functions of CUDs during the high-risk periods of adolescence, emerging adulthood and young adulthood based on data from a large prospective community sample.
Probands (n = 816) from the Oregon Adolescent Depression Project (OADP) participated in four diagnostic assessments (T1–T4) between the ages of 16 and 30 years, during which current and past CUDs were assessed.
The weighted lifetime prevalence of CUDs was 19.1% with an average onset age of 18.6 years. Although gender was not significantly related to the age of initial CUD onset, men were more likely to be diagnosed with a lifetime CUD. Of those diagnosed with a CUD episode, 81.8% eventually achieved recovery during the study period. Women achieved recovery significantly more quickly than men. The recurrence rate (27.7%) was relatively modest, and most likely to occur within the first 36 months following the offset of the first CUD episode. CUD recurrence was uncommon after 72 months of remission and recovery.
CUDs are relatively common, affecting about one out of five persons in the OADP sample prior to the age of 30 years. Eventual recovery from index CUD episodes is the norm, although about 30% of those with a CUD exhibit a generally persistent pattern of problematic use extending 7 years or longer.
Conversion of biomass to electricity is often not economically feasible as a result of large transportation costs and low output prices. We build a model of an adaptable biorefinery situated at an agri-processing facility that already has biomass on-site and consider the optimal scale of the plant to achieve a price premium by selling peaking power given uncertain biomass deliveries year over year as a result of climatic variability. We find that, for conservative electricity prices, a plant situated near cotton gins in Texas could operate with positive expected net revenue while converting on average only 38% of available biomass for peak electricity prices.
An understanding of the mechanisms regulating milk yield in sows is crucial for producers to make the best management decisions during lactation. Suckling of mammary glands by piglets is one factor that is essential for development of these glands during lactation and for the maintenance of lactation in sows. The process of mammary development is not static as the majority of it takes place in the last third of gestation, continues during lactation, is followed by involution at weaning and starts over again in the next gestation. During involution, the mammary glands undergo a rapid and drastic regression in parenchymal tissue, and this can also occur during lactation if a gland is not suckled regularly. Indeed, the pattern of regression is similar for glands that involute at weaning or during lactation. Suckling during 12 to 14 h postpartum is insufficient to maintain lactation and the process of involution that occurs in early lactation is reversible within 1 day of farrowing but is irreversible if a gland is not used for 3 days. However, milk yield from a gland which is ‘rescued’ within the first 24 h remains lower throughout lactation. Suckling does not only affect milk yield in the ongoing lactation, but it also seems to affect that of the next lactation. Indeed, non-suckling of a mammary gland in first-parity sows decreased development and milk yield of that gland in second parity. Nursing behaviour of piglets in early lactation was also affected, where changes were indicative of piglets in second parity being hungrier when suckling glands that were not previously used. It is not known, however, if the same effects would be seen between the second and third lactation. Furthermore, the minimum suckling period required to ensure maximal milk yield from a gland in the next lactation is not known. This review provides an update on our current knowledge of the importance of suckling for mammary development and milk yield in swine.
Phytoestrogens could be a useful tool in swine husbandry practices because of their structural and functional similarities to estradiol. The goal of this study was to compare various routes and doses of administration of the phytoestrogen genistein in sows of two different physiological statuses. Circulating concentrations of isoflavones, estradiol and IGF-I were determined. In experiment 1, 65 sows were equally divided into the five following groups, between days 3 and 5 of the first or second estrous cycle post weaning: (1) controls (CTL); (2) 1 g of genistein fed daily (OR1); (3) 2 g of genistein fed daily (OR2); (4) two daily i.m. injections of 200 mg of genistein (IM400); and (5) two daily i.m. injections of 400 mg of genistein (IM800). Treatments were carried out for 10 days. In experiment 2, 10 sows were equally divided into two groups on day 90 of gestation, namely, controls (CTL) or 2 g of genistein fed daily for 10 days (OR2). In both trials, jugular blood samples were collected on days 1 (before treatment), 5 and 10 at 0730 h. In experiment 1, a blood sample was also collected at 1730 h on day 10 for CTL, IM400 and IM800 sows. In experiment 1, circulating concentrations of genistein on days 5 and 10 were greater in OR2, IM400 and IM800 than in CTL and OR1 group sows (P < 0.01). Daily dietary supplementation with 2 g of genistein resulted in blood concentrations that were similar to those in animals given daily two i.m. injections of 200 mg. Values of all isoflavones, except equol, which was not detectable, were greater in PM than in AM on day 10 (P < 0.01). In experiment 2, genistein concentrations were greater in OR2 compared with CTL on days 5 and 10 (P ⩽ 0.05). There was no difference in the genistein response to OR2 because of physiological status (i.e. weaned v. gestating, P > 0.1). Estradiol and IGF-I concentrations were not altered by any of the treatments (P > 0.1). Providing genistein either per os or via i.m. injections increased circulating concentrations of genistein in female swine within 5 days of the onset of treatment. The genistein response to i.m. injections of genistein was similar in weaned and late-pregnant sows, even though endogenous concentrations of estradiol differed. This response was specific in that estradiol, IGF-I and isoflavones other than genistein were not affected by treatments.
Although usually thought of as external environmental stressors, a significant heritable component has been reported for measures of stressful life events (SLEs) in twin studies.
We examined the variance in SLEs captured by common genetic variants from a genome-wide association study (GWAS) of 2578 individuals. Genome-wide complex trait analysis (GCTA) was used to estimate the phenotypic variance tagged by single nucleotide polymorphisms (SNPs). We also performed a GWAS on the number of SLEs, and looked at correlations between siblings.
A significant proportion of variance in SLEs was captured by SNPs (30%, p = 0.04). When events were divided into those considered to be dependent or independent, an equal amount of variance was explained for both. This ‘heritability’ was in part confounded by personality measures of neuroticism and psychoticism. A GWAS for the total number of SLEs revealed one SNP that reached genome-wide significance (p = 4 × 10−8), although this association was not replicated in separate samples. Using available sibling data for 744 individuals, we also found a significant positive correlation of R2 = 0.08 in SLEs (p = 0.03).
These results provide independent validation from molecular data for the heritability of reporting environmental measures, and show that this heritability is in part due to both common variants and the confounding effect of personality.