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BACKGROUND: Adverse pregnancy outcomes (APO) contribute to higher risk of maternal cerebrovascular disease, but longitudinal data that include APO and stroke timing are lacking. We hypothesized that APO are associated with younger age at first stroke, with a stronger relationship in those with >1 pregnancy with APO. METHODS: We analyzed longitudinal Finnish nationwide health registry data from the FinnGen Study. We included women who gave birth after 1969 when the hospital discharge registry was established. We defined APO as a pregnancy affected by gestational hypertension, preeclampsia, eclampsia, preterm birth, small for gestational age infant, or placental abruption. We defined stroke as first hospital admission for ischemic stroke or nontraumatic intracerebral or subarachnoid hemorrhage, excluding stroke during pregnancy or within 1 year postpartum. We used Kaplan-Meier survival curves and multivariable-adjusted Cox and generalized linear models to assess the relationship between APO and future stroke. RESULTS: We included 144 306 women with a total of 316 789 births in the analysis sample, of whom 17.9% had at least 1 pregnancy with an APO and 2.9% experienced an APO in ≥2 pregnancies. Women with APO had more comorbidities including obesity, hypertension, heart disease, and migraine. Median age at first stroke was 58.3 years in those with no APO, 54.8 years in those with 1 APO, and 51.6 years in those with recurrent APO. In models adjusted for sociodemographic characteristics and stroke risk factors, risk of stroke was greater in women with 1 APO (adjusted hazard ratio, 1.3 [95% CI, 1.2–1.4]) and recurrent APO (adjusted hazard ratio, 1.4 [95% CI, 1.2–1.7]) compared with those with no APO. Women with recurrent APO had more than twice the stroke risk before age 45 (adjusted odds ratio, 2.1 [95% CI, 1.5–3.1]) compared with those without APO. CONCLUSIONS: Women who experience APO have earlier onset of cerebrovascular disease, with the earliest onset in those with more than 1 affected pregnancy.

ObjectivesTo recontact biobank participants and collect cognitive, behavioural and lifestyle information via a secure online platform.DesignBiobank-based recontacting pilot study.SettingThree Finnish biobanks (Helsinki, Auria, Tampere) recruiting participants from February 2021 to July 2021.ParticipantsAll eligible invitees were enrolled in FinnGen by their biobanks (Helsinki, Auria, Tampere), had available genetic data and were >18 years old. Individuals with severe neuropsychiatric disease or cognitive or physical disabilities were excluded. Lastly, 5995 participants were selected based on their polygenic score for cognitive abilities and invited to the study. Among invitees, 1115 had successfully participated and completed the study questionnaire(s).Outcome measuresThe primary outcome was the participation rate among study invitees. Secondary outcomes included questionnaire completion rate, quality of data collected and comparison of participation rate boosting strategies.ResultsThe overall participation rate was 18.6% among all invitees and 23.1% among individuals aged 18–69. A second reminder letter yielded an additional 9.7% participation rate in those who did not respond to the first invitation. Recontacting participants via an online healthcare portal yielded lower participation than recontacting via physical letter. The completion rate of the questionnaire and cognitive tests was high (92% and 85%, respectively), and measurements were overall reliable among participants. For example, the correlation (r) between self-reported body mass index and that collected by the biobanks was 0.92.ConclusionIn summary, this pilot suggests that recontacting FinnGen participants with the goal to collect a wide range of cognitive, behavioural and lifestyle information without additional engagement results in a low participation rate, but with reliable data. We suggest that such information be collected at enrolment, if possible, rather than via post hoc recontacting.

Population isolates such as Finland provide benefits in genetic studies because the allelic spectrum of damaging alleles in any gene is often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%), which survived the founding bottleneck, as opposed to being distributed over a much larger number of ultra--rare variants. While this advantage is well-- established in Mendelian genetics, its value in common disease genetics has been less explored. FinnGen aims to study the genome and national health register data of 500,000 Finns, already reaching 224,737 genotyped and phenotyped participants. Given the relatively high median age of participants (63 years) and dominance of hospital-based recruitment, FinnGen is enriched for many disease endpoints often underrepresented in population-based studies (e.g., rarer immune-mediated diseases and late onset degenerative and ophthalmologic endpoints). We report here a genome-wide association study (GWAS) of 1,932 clinical endpoints defined from nationwide health registries. We identify genome--wide significant associations at 2,491 independent loci. Among these, finemapping implicates 148 putatively causal coding variants associated with 202 endpoints, 104 with low allele frequency (AFWe studied a benchmark set of 15 diseases that had previously been investigated in large genome-wide association studies. FinnGen discovery analyses were meta-analysed in Estonian and UK biobanks. We identify 30 novel associations, primarily low-frequency variants strongly enriched, in or specific to, the Finnish population and Uralic language family neighbors in Estonia and Russia.These findings demonstrate the power of bottlenecked populations to find unique entry points into the biology of common diseases through low-frequency, high impact variants. Such high impact variants have a potential to contribute to medical translation including drug discovery.

A wealth of biospecimen samples are stored in modern globally distributed biobanks. Biomedical researchers worldwide need to be able to combine the available resources to improve the power of large-scale studies. A prerequisite for this effort is to be able to search and access phenotypic, clinical and other information about samples that are currently stored at biobanks in an integrated manner. However, privacy issues together with heterogeneous information systems and the lack of agreed-upon vocabularies have made specimen searching across multiple biobanks extremely challenging. We describe three case studies where we have linked samples and sample descriptions in order to facilitate global searching of available samples for research. The use cases include the ENGAGE (European Network for Genetic and Genomic Epidemiology) consortium comprising at least 39 cohorts, the SUMMIT (surrogate markers for micro- and macro-vascular hard endpoints for innovative diabetes tools) consortium and a pilot for data integration between a Swedish clinical health registry and a biobank. We used the Sample avAILability (SAIL) method for data linking: first, created harmonised variables and then annotated and made searchable information on the number of specimens available in individual biobanks for various phenotypic categories. By operating on this categorised availability data we sidestep many obstacles related to privacy that arise when handling real values and show that harmonised and annotated records about data availability across disparate biomedical archives provide a key methodological advance in pre-analysis exchange of information between biobanks, that is, during the project planning phase. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Data sharing is essential for the conduct of cutting-edge research and is increasingly required by funders concerned with maximising the scientific yield from research data collections. International research consortia are encouraged to share data intra-consortia, inter-consortia and with the wider scientific community. Little is reported regarding the factors that hinder or facilitate data sharing in these different situations. This paper provides results from a survey conducted in the European Network for Genetic and Genomic Epidemiology (ENGAGE) that collected information from its participating institutions about their data-sharing experiences. The questionnaire queried about potential hurdles to data sharing, concerns about data sharing, lessons learned and recommendations for future collaborations. Overall, the survey results reveal that data sharing functioned well in ENGAGE and highlight areas that posed the most frequent hurdles for data sharing. Further challenges arise for international data sharing beyond the consortium. These challenges are described and steps to help address these are outlined.

Yeast cell immobilization causes changes in several cellular physiological properties, resulting in severely unbalanced flavor profiles of beers produced in immobilized-cell systems. To explore the reasons for the altered production of flavor-active metabolites, such as volatile esters, the transcription rates of several genes were measured in free and immobilized cells. Expression profiles of the stress-related genes HSP12 and SSA3 revealed that cell immobilization exerted certain stresses on the yeast cells, possibly nutrient starvation and osmotic stress. However, yeast cells may also benefit from the protecting effect of the immobilization matrix, since without a protecting matrix, the free cells in the standard free-cell system showed a stronger induction of HSP12, a general stress marker, compared with the immobilized cells. In accordance with the lower stress gene expression levels, the immobilized cells accumulated trehalose as low as 26% of that of the standard free cells. The expression level of ATF1, encoding alcohol acetyl transferase I, was significantly raised in the immobilized cells, resulting in a twofold increase of iso-amyl acetate formation. The activity of ATF1 is regulated by the protein kinases Sch9p and PKA, involved in stress responses and nutrient-sensing signaling pathways. The particular microenvironment created by cell immobilization thus possibly activates the cAMP/PKA/Sch9 pathway, resulting in an induction of ATF1 expression leading to enhanced ester concentrations in the final fermentation product.

Previous results have indicated that supplementation of stationary-phase cropped brewer's yeast with the unsaturated fatty acid linoleic acid is a good alternative to wort aeration with respect to its fermentation performance in a subsequent fermentation cycle. The experiments were carried out with a well-defined fermentation medium. Here, we show that, also with beer wort, the cropped yeast that was suspended in fermented wort and under nongrowing conditions rapidly incorporated the exogenous y acid. Linoleic acid is also taken up by spheroplasts, which excludes the possibility that it is adsorbed onto the cell walls. The intracellular localization of linoleic acid was studied. It was rapidly recovered from the free fatty acids pool, diglycerides, triglycerides, and phospholipids. The highest amounts were recovered from the neutral lipids and the free fatty acids fractions. The results obtained with yeast first grown under stirred conditions were the same as those obtained with yeast grown under nonstirred conditions. The results with the stationary-phase cells are discussed with respect to results obtained with cropped yeast suspended in fresh wort under growing conditions. Some differences in uptake were also found when the cropped yeast was suspended and supplemented in water rather than in fermented wort. Further studies are required to investigate the fermentation performance of the supplemented yeast in a subsequent fermentation cycle.

A novel bioreactor with immobilization matrices was constructed to study physiological differences between immobilized and free cells and to compare the fermentation behavior of the immobilized-cel...

Most breweries collect yeast from a previous fermentation cycle for further use in a subsequent cycle. However, the cropped cells are deficient in membrane sterols and unsaturated fatty acids (UFAs) which are required for good fermentation performance in the next cycle. Consequently, the cellular levels of these compounds must be restored to obtain an optimal fermentation performance. There are currently three possibilities to satisfy this requirement. The common practice is aeration of the wort before pitching, thus providing oxygen needed for lipid synthesis during the first stages of fermentation. Oxygenation (aeration) of cropped yeast slurries is a second alternative. Finally, the addition of the required lipids to wort is sometimes suggested as an alternative to aeration. We examined a fourth possibility, namely the supplementation with UFA of cropped cells. Previously, we reported that the supplementation of stationary phase cropped brewer's yeast with linoleic acid is a good alternative to wort aeration. This conclusion resulted from results obtained with a well-defined stirred synthetic fermentation medium. We also showed that cells cropped from non-stirred tall-tube fermented malt wort incorporated linoleic acid into different cellular lipid fractions, when suspended and supplemented in fermented wort. Now, we report that such yeast, pitched in malt wort in non-stirred tall-tubes, showed growth and attenuation profiles comparable to unsupplemented yeast in pre-aerated wort. Moreover, the synthesis of acetate esters, which is known to be affected when UFAs are added directly to the wort, was not significantly affected. We hypothesize that the active uptake of linoleic acid during fermentation and its activation by coenzyme A (CoA) and phospholipid synthesis are responsible for the effects on ester synthesis, through repression of the alcohol acetyltransferase-encoding gene, ATF1. In supplemented cropped yeast, these reactions occur prior to fermentation, thus avoiding interferences with acetate ester synthesis. In serial repitching experiments with repeated linoleic acid supplementation of the cropped yeast, the fermentation performances of the yeast remained comparable to those of non-supplemented yeast in pre-aerated wort. However, due to a progressive increase of cellular UFA, negative effects on acetate ester synthesis appeared. Nevertheless, the supplementation of cropped yeast with UFAs can be considered as an interesting alternative to wort oxygenation to restore optimal membrane functions.

Immobilised-cell fermentors offer great benefits compared to traditional free-cell systems. However, a major problem is unbalanced flavour production when these fermentors are used for the production of alcoholic beverages. One of the keys to obtaining better control over flavour formation may be the concentration of dissolved CO2, which has inhibitory effects on yeast growth and metabolism. This article demonstrates that the presence of immobilisation matrices facilitates the removal of CO2 from the liquid medium, which results in a low level of dissolved CO2 during fermentation. Moreover, the formation of volatile higher alcohols and esters was greatly enhanced in the immobilised-cell system when compared to the free cell system. By sparging a CO2 flow (45 ml/min) into the immobilised-cell system, cell growth was reduced by 10–30% during the active fermentation stage, while the fermentation rate was unaffected. The uptake of branched-chain amino acids was reduced by 8–22%, and the formation of higher alcohols and esters was reduced on average by 15% and 18%, respectively. The results of this study suggest that mismatched flavour profiles with immobilised-cell systems can be adjusted by controlling the level of dissolved CO2 during fermentation with immobilised yeast.