Genetics of Estrogen-Related Traits; From Candidate Genes to GWAS

In the first part of this thesis, the association of polymorphisms in three candidate genes (estrogen receptor alpha (ESR1), retinoblastoma interacting zinc finger domain (RIZ1) and catechol-O-methyltransferase (COMT)) with estradiol levels, age at natural menopause, BMD and fracture risk in the Rotterdam Study is shown. For the ESR1 gene, fine-mapping of the PvuII and XbaI LD-block is presented, together with a haplotype analysis, showing that one additional SNP in the promoter region of the gene could distinguish a third haplotype in the previously defined PvuII–XbaI haplotype 1 and explain the associations we found before. In another study it was shown that the Pro704 insertion-deletion polymorphism in RIZ1 was not associated with BMD or fracture risk in men and women. The third study showed that the Met158Val polymorphism in the estradiol degrading enzyme COMT was associated with fracture risk, independent of BMD. In the last part genome-wide association studies (GWAS) for sex hormone binding globuline, age at menarche and age at natural menopause are presented. A GWAS on sex-hormone-binding-globuline (SHBG) levels showed highly significant associations of several SNPs in the SHBG-gene region with plasma SHBG-levels. A study on age at menarche in 17,510 women of seven studies from the CHARGE consortium identified two loci with P<5x10-8. A genome-wide association study for age at natural menopause in 2,979 European women identified three loci located on chromosome 13, 19 and 20 associated with age at natural menopause. The three loci have not been indicated to play a role in natural menopause before, and therefore the functional mechanism underlying these associations remains unknown

A short note on the nested-sweep polarized traces method for the 2D Helmholtz equation

We present a variant of the solver in Zepeda-N\'u\~nez and Demanet (2014), for the 2D high-frequency Helmholtz equation in heterogeneous acoustic media. By changing the domain decomposition from a layered to a grid-like partition, this variant yields improved asymptotic online and offline runtimes and a lower memory footprint. The solver has online parallel complexity that scales \emph{sub linearly} as $\mathcal{O} \left( \frac{N}{P} \right)$, where $N$ is the number of volume unknowns, and $P$ is the number of processors, provided that $P = \mathcal{O}(N^{1/5})$. The variant in Zepeda-N\'u\~nez and Demanet (2014) only afforded $P = \mathcal{O}(N^{1/8})$. Algorithmic scalability is a prime requirement for wave simulation in regimes of interest for geophysical imaging.Comment: 5 pages, 5 figure

Motives of contributing personal data for health research:(non-)participation in a Dutch biobank

BACKGROUND: Large-scale, centralized data repositories are playing a critical and unprecedented role in fostering innovative health research, leading to new opportunities as well as dilemmas for the medical sciences. Uncovering the reasons as to why citizens do or do not contribute to such repositories, for example, to population-based biobanks, is therefore crucial. We investigated and compared the views of existing participants and non-participants on contributing to large-scale, centralized health research data repositories with those of ex-participants regarding the decision to end their participation. This comparison could yield new insights into motives of participation and non-participation, in particular the behavioural change of withdrawal. METHODS: We conducted 36 in-depth interviews with ex-participants, participants, and non-participants of a three-generation, population-based biobank in the Netherlands. The interviews focused on the respondents' decision-making processes relating to their participation in a large-scale, centralized repository for health research data. RESULTS: The decision of participants and non-participants to contribute to the biobank was motivated by a desire to help others. Whereas participants perceived only benefits relating to their participation and were unconcerned about potential risks, non-participants and ex-participants raised concerns about the threat of large-scale, centralized public data repositories and public institutes, such as social exclusion or commercialization. Our analysis of ex-participants' perceptions suggests that intrapersonal characteristics, such as levels of trust in society, participation conceived as a social norm, and basic societal values account for differences between participants and non-participants. CONCLUSIONS: Our findings indicate the fluidity of motives centring on helping others in decisions to participate in large-scale, centralized health research data repositories. Efforts to improve participation should focus on enhancing the trustworthiness of such data repositories and developing layered strategies for communication with participants and with the public. Accordingly, personalized approaches for recruiting participants and transmitting information along with appropriate regulatory frameworks are required, which have important implications for current data management and informed consent procedures

Infection by Wolbachia bacteria and its influence on the reproduction of the stored-product psocid, Liposcelis tricolor

Wolbachia are maternally inherited intracellular bacteria that infect a wide range of arthropods and nematodes and are associated with various reproductive abnormalities in their hosts. The infection by Wolbachia of the psocid, Liposcelis tricolor (Psocoptera: Liposcelididae), was investigated using long PCR amplification of the wsp gene that codes for a Wolbachia surface protein. The results showed that L. tricolor was positive for Wolbachia. Phylogenetic analysis showed that the Wolbachia found in L. tricolor was related to the B-group. Wolbachia infection in L. tricolor could be removed through antibiotic treatment. The results of crosses including ♀W+ x ♂ W+, ♀ W− x ♂W+, ♀ W+ x ♂ W−, and ♀W− x ♂ W−, suggested that the removal of Wolbachia resulted in lower egg production by L. tricolor. The mean embryonic mortality of offspring produced by L. tricolor without Wolbachia was significantly higher than that of control

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OBJECTIVE: to investigate the association of life events during pregnancy with change in antenatal anxiety and depression symptoms. We distinguished pregnancy related and non-pregnancy related events and assessed specificity of these associations for depressive or anxious symptoms. In addition, we investigated whether the associations were affected by personality or childhood adversities. DESIGN: observational prospective cohort study SETTING: primary and secondary obstetric care centres in the Netherlands PARTICIPANTS: 1603 women during their first trimester of pregnancy between May 2010 and May 2012 MEASUREMENTS AND FINDINGS: we performed linear regression analyses to test the associations of pregnancy related, non-pregnancy related life events, childhood adversities and the personality traits neuroticism and extraversion with the change in symptoms of anxiety (State Trait Anxiety Inventory) and depression (Edinburgh Postnatal Depression Scale) from week 12 to week 36. Life events during pregnancy were associated with increasing antenatal symptoms of anxiety and depression. Effect sizes associated with the highest numbers of events observed ranged from 0.59 to 1.31. Pregnancy related events were specifically associated with increasing symptoms of anxiety (p=0.009), whereas non-pregnancy related events were merely associated with an increase in symptoms of depression (p<0.001). Neither personality traits nor childhood trauma influenced the associations under study. KEY CONCLUSIONS: the most important finding is that pregnancy related life events during pregnancy increase levels of antenatal anxiety, whereas depression levels increase when women experience life events that are unrelated to pregnancy. Furthermore, non-pregnancy related events show stronger associations with increases in symptoms of anxiety or depression compared to pregnancy related events. IMPLICATIONS FOR PRACTICE: our findings may help midwives to tailor psychosocial care to the specific risks of the pregnant woman which may eventually have a positive impact on the health of mother and child