Finnish Population Research Articles

Psychotherapy duration and work disability: A prospective Finnish register study.

The influence of psychotherapy duration on common mental disorder (CMD) outcomes remains a topic of ongoing debate. Whereas most research has focused on CMD symptom change, the evidence on the psychotherapy duration of subsequent CMD-related work disability and the change in psychotropic drug purchases is scarce. We used a register-based cohort representing 33% of the Finnish population. The participants included working-age individuals (N = 12,047, 76% women, mean age = 36) who initiated long-term psychotherapy, between 2014 and 2017. They were followed from 2011 to 2021 and psychotherapy duration ranged from less than a year to over 3 years. We used an interrupted time series design to analyze the psychotherapy duration-dependent changes in CMD-related work disability (primary outcome, operationalized as depression or anxiety-related sickness absence, SA, days) and the annual number of psychotropic drug purchases or distinct drugs purchased (secondary outcomes). There were no differences in the levels of work disability or drug purchases before the psychotherapy. We observed a decreasing level and trend in all outcomes across all psychotherapy duration groups. The largest decline in level was observed in the <1-year duration group (88% decline for SA and 43%-44% for drug purchases) while the smallest decline was in the 3+ years duration group (73% for SA and 27% for drug purchases). Work disability outcomes and duration varied among individuals, even with similar initial mental health-related work disability or use of auxiliary psychotropic treatments. Compared to longer psychotherapy, shorter psychotherapy was associated with sharper improvements.

(056) The Association Between Disgust Sensitivity, Sexual Desire, Relationship Satisfaction in Finland

Abstract Introduction Disgust is a basic emotion directed towards certain objects to avoid harm (Angyal, 1941), mainly pathogens. Research, however, has proposed a heterogeneity of disgust beyond pathogen avoidance to generate the functional model, which proposed the functionally distinct domains of disgust: moral, pathogen, and sexual. This model proposes that sexual disgust is an avoidance of sexual contact with unfit partners that may yield unfit offspring (Tybur &amp; de Vries, 2013), this may be due to other anxiety related disorders (Davey, 2011 and Troop et al., 2002) Objective This study focuses on the association between disgust sensitivity with sexual desire, and relationships satisfaction. Hypothesis: elevated levels of disgust sensitivity are negatively associated with sexual desire and relationship satisfaction. Methods Invitation letters were sent out to the registered Finnish population in the Finnish Central Population Registry to participate in a(n) (online) survey, 9,319 individuals responded to the invitation and completed the survey and agreed to participate in the research. The tools used in this study were Perceived Relationship Quality Component (PRQC), Sexual Desire Inventory (SDI), and the Three-Disgust Domain Scale (TDDS). Results The results indicate that the sexual desire and sexual disgust sensitivity, are negatively correlated, the relationship satisfaction correlations are positive except the men pathogen disgust which is a negative correlation between pathogen disgust sensitivity and relationship satisfaction. The correlation between the study variables indicated that among men and women sexual disgust is negatively correlated with sexual desire, and the correlation of relationship satisfaction and sexual disgust was positively correlated. Conclusions The results show the negative association of sexual disgust with sexual desire, but there is a positive relationship between sexual disgust and relationship satisfaction. Disclosure No.

Skin cancers and their precursors in Finnish liver transplantation recipients: A follow‐up study

AbstractBackgroundThe incidence of skin cancers in transplant recipients is known to have increased compared to the general population. Risk factors include age at the time of transplantation, duration and dose of immunosuppressive medication. Research data on the incidence of skin cancer precursors in transplant recipients is limited.ObjectivesWe aimed to investigate the incidence of skin cancers and their precursors and the factors influencing their development in Finnish liver transplant recipients.MethodsWe recruited 140 volunteers who were over 18 years old at the time of the study and had been transplanted at least 5 years before. Patients were examined by a dermatologist between 2012 and 2016 and, if necessary, followed up based on cutaneous findings. All patients in the study were followed up until May 2021 or until the death of the patient, based on medical records.ResultsThe study found an increased incidence of nonmelanoma skin cancers (NMSCs), especially of squamous cell carcinoma, in liver transplantation (LT) recipients compared to the general Finnish population (squamous cell carcinoma SIR 21.2, basal cell carcinoma SIR 7.6). Precursors of squamous cell carcinoma were found in 43 patients (30.7%) after transplantation. The study found no statistically significant difference between the drugs used for immunosuppression.ConclusionsOur data showed an increased risk of NMSCs in LT recipients. After LT, patients are at significant risk of SCC and its precursors may be found even in almost third of patients in 17.5 years follow‐up. Given this information, it is considered important to monitor LTRs with adequate frequency to treat precursors as early as possible before the development of SCC.

Religion and Fertility: A Longitudinal Register Study Examining Differences by Sex, Parity, Partner's Religion, and Religious Conversion in Finland.

We use longitudinal data on religious affiliation in Finland to examine childbearing behavior. All analyses are based on detailed fertility information from the Finnish national register of each person's religious denomination for men and women born in 1956-1975. We identify higher fertility according to parity among members of the Evangelical Lutheran state church and other Protestant churches, and lower fertility among individuals with no religious affiliation. Most other religious groups-Orthodox Christians, Jews, Muslims, and adherents of Eastern religions-have intermediate levels of fertility. We also find that religious converts, that is, those observed with more than one religious denomination over their life course, typically are similar to the non-converts of the group they convert to, though with more distinct deviations from the Finnish population. Women show larger differences by religious affiliation than men. We find the largest differences across religions when we examine the proportion of childless men and women. Overall, differences between religious groups are rather modest, and childbearing patterns are quite similar. Our results provide, to our knowledge, the first examination of religion and fertility using national-level longitudinal data.

Global carrier frequency and predicted genetic prevalence of patients with pathogenic sequence variants in autosomal recessive genetic neuromuscular diseases

Genetic neuromuscular diseases are clinically and genetically heterogeneous genetic disorders that primarily affect the peripheral nerves, muscles, and neuromuscular junctions. This study aimed to identify pathogenic variants, calculate carrier frequency, and predict the genetic prevalence of autosomal recessive neuromuscular diseases (AR-NMDs). We selected 268 AR-NMD genes and analyzed their genetic variants sourced from the gnomAD database. After identifying the pathogenic variants using an algorithm, we calculated the carrier frequency and predicted the genetic prevalence of AR-NMDs. In total, 10,887 pathogenic variants were identified, including 3848 literature verified and 7039 manually verified variants. In the global population, the carrier frequency of AR-NMDs is 32.9%, with variations across subpopulations ranging from 22.4% in the Finnish population to 36.2% in the non-Finnish European population. The predicted genetic prevalence of AR-NMDs was estimated to be 24.3 cases per 100,000 individuals worldwide, with variations across subpopulations ranging from 26.5 to 41.4 cases per 100,000 individuals in the Latino/Admixed American and the Ashkenazi Jewish populations, respectively. The AR-NMD gene with the highest carrier frequency was GAA (1.3%) and the variant with the highest allele frequency was c.-32-13 T>G in GAA with 0.0033 in the global population. Our study revealed a higher-than-expected frequency of AR-NMD carriers, constituting approximately one-third of the global population, highlighting ethnic heterogeneity in genetic susceptibility.

Genetic Analysis of Obstructive Sleep Apnea and Its Relationship with Severe COVID-19.

Rationale: Although patients with obstructive sleep apnea (OSA) have a higher risk for coronavirus disease (COVID-19) hospitalization, the causal relationship has remained unexplored. Objectives: To understand the causal relationship between OSA and COVID-19 by leveraging data from vaccination and electronic health records, genetic risk factors from genome-wide association studies, and Mendelian randomization. Methods: We elucidated genetic risk factors for OSA using FinnGen (total N = 377,277), performing genome-wide association. We used the associated variants as instruments for univariate and multivariate Mendelian randomization (MR) analyses and computed absolute risk reduction against COVID-19 hospitalization with or without vaccination. Results: We identified nine novel loci for OSA and replicated our findings in the Million Veteran Program. Furthermore, MR analysis showed that OSA was a causal risk factor for severe COVID-19 (P = 9.41 × 10-4). Probabilistic modeling showed that the strongest genetic risk factor for OSA at the FTO locus reflected a signal of higher body mass index (BMI), whereas BMI-independent association was seen with the earlier reported SLC9A4 locus and a MECOM locus, which is a transcriptional regulator with 210-fold enrichment in the Finnish population. Similarly, multivariate MR analysis showed that the causality for severe COVID-19 was driven by BMI (multivariate MR P = 5.97 × 10-6, β = 0.47). Finally, vaccination reduced the risk for COVID-19 hospitalization more in the patients with OSA than in the non-OSA controls, with respective absolute risk reductions of 13.3% versus 6.3%. Conclusions: Our analysis identified novel genetic risk factors for OSA and showed that OSA is a causal risk factor for severe COVID-19. The effect is predominantly explained by higher BMI and suggests BMI-dependent effects at the level of individual variants and at the level of comorbid causality.

Miscarriage risk assessment: a bioinformatic approach to identifying candidate lethal genes and variants

PurposeMiscarriage, often resulting from a variety of genetic factors, is a common pregnancy outcome. Preconception genetic carrier screening (PGCS) identifies at-risk partners for newborn genetic disorders; however, PGCS panels currently lack miscarriage-related genes. In this study, we evaluated the potential impact of both known and candidate genes on prenatal lethality and the effectiveness of PGCS in diverse populations.MethodsWe analyzed 125,748 human exome sequences and mouse and human gene function databases. Our goals were to identify genes crucial for human fetal survival (lethal genes), to find variants not present in a homozygous state in healthy humans, and to estimate carrier rates of known and candidate lethal genes in various populations and ethnic groups.ResultsThis study identified 138 genes in which heterozygous lethal variants are present in the general population with a frequency of 0.5% or greater. Screening for these 138 genes could identify 4.6% (in the Finnish population) to 39.8% (in the East Asian population) of couples at risk of miscarriage. This explains the cause of pregnancy loss in approximately 1.1–10% of cases affected by biallelic lethal variants.ConclusionThis study has identified a set of genes and variants potentially associated with lethality across different ethnic backgrounds. The variation of these genes across ethnic groups underscores the need for a comprehensive, pan-ethnic PGCS panel that includes genes related to miscarriage.

Stability of morningness/eveningness and changes in sleep and mental health during mid-adulthood.

Objective: A change toward Eveningness in circadian sleep-wake behavior is generally seen from childhood to adolescence, but less is known about circadian changes during adulthood. Circadian changes during mid-adulthood are of high interest, since Eveningness associates with a range of health-related problems, including psychological symptoms and mental disorders. In this study, we examined the circadian stability across 10 years, from 42 to 52 years of age, and how it is associated with sleep and mental health in a Finnish general population cohort follow-up-based (n = 976). Method: Circadian type was assessed at both ages with a widely used item for self-estimated Morningness/Eveningness from the original Horne-Östberg Morningness-Eveningness Questionnaire. Generalized estimating equations were used for analyzing how a change in Morningness/Eveningness was associated with sleep and mental health longitudinally. Results: Our findings indicate that the circadian type is a highly stable trait during mid-adulthood with mainly moderate changes occurring in 42.2% of adults and no circadian change among 57.8% of adults. Most changes occurred within the same circadian type (23.9%), second to changes between moderate circadian types (13.3%). Changes between the Definite Evening-types and Morning-types were very rare (0.5%). Stable Evening-types reported more insufficient sleep, discrepancy between sleep duration on workdays and free days, and depression as compared to stable Morning-types. Moderate changes toward Morningness, comprising mostly those within Morning-types, were associated with reduced distress and psychological symptoms. Conclusions: In conclusion, our findings show high stability of mid-adulthood circadian type. However, changes toward Morningness seem to be associated with improved mental health. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Collectivization in USSR: Practice and Ideology, Some Aspects of its Impact on Rural Society

The article provides a comprehensive overview of the main approaches developed in historiography to understand the process of collectivization in the USSR, which determined several specific features of the transition of the domestic society from an agrarian phase to an industrial one. Arguing for the viability of the New Economic Policy’s rural economy and the deadlock of Stalin’s version of its collectivization, the author relies on the inherent “sympractical” type of peasant culture. The historically developed worldview of rural community members formed the basis for high labor motivation. The destruction of this worldview during the process of collectivization became the cause of tragedy. The article presents the results of a comparative analysis of two stages of socialist transformation in the village. It examines the destructive impact of the expropriation of peasants on the economy in the first stage and explores the issues of crisis resolution in the second stage through the removal of certain restrictions on private farming. The article analyzes the factors of social degradation in the Soviet countryside in the 1930s and identifies their manifestation in interethnic relations. The novelty of the research lies in the author’s examination, based on the materials from the declassified “special file” of the Leningrad Regional Committee of the CPSU(B) in the 2000s, of peculiar manifestations of collectivization contradictions in the fate of the Finnish population in the Leningrad region.

Previous cancers in women diagnosed with premature ovarian insufficiency: A nationwide population-based case-control study.

To investigate the occurrence of previous cancer diagnoses in women suffering from premature ovarian insufficiency (POI) and compare it with the general population, shedding light on the association between cancer, cancer treatments, and POI. We conducted a nationwide case-control study based on registry data from various sources, including the Social Insurance Institution, Finnish Population Information System, and Finnish Cancer Registry spanning from 1953 to 2018. Our participants comprised all women in Finland who, between 1988 and 2017, received hormone replacement therapy reimbursement for ovarian insufficiency before the age of 40 years (n = 5221). Controls, matched in terms of age and municipality of residence, were selected from the Finnish Population Information System (n = 20 822). Our main exposure variable was a history of cancer diagnosis preceding the diagnosis of POI. We analyzed odds ratios (OR) to compare the prevalence of previous cancers in women with POI with that in controls, stratifying results based on cancer type, age at cancer diagnosis, and the time interval between cancer diagnosis and POI. We also assessed changes in OR for previous cancer diagnoses over the follow-up period. Out of the women diagnosed with POI, 21.9% had previously been diagnosed with cancer, resulting in an elevated OR of 36.5 (95% confidence interval [CI] 30.9 to 43.3) compared with 0.8% of the controls. The risk of developing POI was most pronounced during the first 2 years following a cancer diagnosis, with an OR of 103 (95% CI 74.1 to 144). Importantly, this risk remained elevated even when the time interval between cancer and POI exceeded 10 years, with an OR of 5.40 (95% CI 3.54 to 8.23). This study reveals that 21.9% of women with POI have a history of cancer, making the prevalence of cancer among these women 27.5 times higher than age-matched controls in the Finnish population. The risk of developing POI is most substantial in the first 2 years following a cancer diagnosis. These findings underscore the role of cancer treatments as an etiological factor for POI and emphasize the importance of recognizing the risk of POI in cancer survivors for early diagnosis and intervention.

Low titer group O whole blood and risk of RhD alloimmunization: Rationale for use in Finland.

Prehospital low-titer group O whole blood (LTOWB) used for patients with life-threatening hemorrhage is often RhD positive. The most important complication following RhD alloimmunization is hemolytic disease of the fetus and newborn (HDFN). Preceding clinical use of RhD positive LTOWB, we estimated the risk of HDFN due to LTOWB prehospital transfusion in the Finnish population. We collected data on prehospital transfusions in Tampere and Helsinki University Hospital areas. Using the mean of reported alloimmunization rates in trauma studies (24%) and a higher reported rate representing trauma patients of 13-50 years old (42.7%), we estimated the risk of HDFN and extrapolated it to the whole of Finland. We estimated that in Finland, with the current prehospital transfusion rate we would see 1-3 cases of severe HDFN due to prehospital LTOWB transfusions every 10 years, and fetal death due to HDFN caused by LTOWB transfusion less than once in 100 years. The estimated risk of serious HDFN due to prehospital LTOWB transfusion in the Finnish population is similar to previous estimates. As Finland routinely screens expectant mothers for red blood cell antibodies and as the contemporary treatment of HDFN is very effective, we support the prehospital use of RhD positive LTOWB in all patient groups.

Risk adjustment for regional healthcare funding allocations with ensemble methods: an empirical study and interpretation

We experiment with recent ensemble machine learning methods in estimating healthcare costs, utilizing Finnish data containing rich individual-level information on healthcare costs, socioeconomic status and diagnostic data from multiple registries. Our data are a random 10% sample (553,675 observations) from the Finnish population in 2017. Using annual healthcare cost in 2017 as a response variable, we compare the performance of Random forest, Gradient Boosting Machine (GBM) and eXtreme Gradient Boosting (XGBoost) to linear regression. As machine learning methods are often seen as unsuitable in risk adjustment applications because of their relative opaqueness, we also introduce visualizations from the machine learning literature to help interpret the contribution of individual variables to the prediction. Our results show that ensemble machine learning methods can improve predictive performance, with all of them significantly outperforming linear regression, and that a certain level of interpretation can be provided for them. We also find individual-level socioeconomic variables to improve prediction accuracy and that their effect is larger for machine learning methods. However, we find that the predictions used for funding allocations are sensitive to model selection, highlighting the need for comprehensive robustness testing when estimating risk adjustment models used in applications.

Genetic testing for familial hypercholesterolemia in a Finnish cohort of patients with premature coronary artery disease and elevated LDL-C levels.

Based on Finnish LDLR-founder variations, the prevalence of familial hypercholesterolemia (FH) in Finland is estimated to be at least 1:600. Patients with FH have increased risk of premature coronary artery disease (CAD) and thus the prevalence of FH is expected to be higher in this subgroup. To assess the prevalence of monogenic FH in a Finnish cohort of patients with premature CAD and elevated low-density lipoprotein cholesterol (LDL-C) levels. Among 28,295 patients undergoing angiography at Heart Hospital at Tampere University Hospital between 2007 and 2017, we identified 162 patients diagnosed with premature CAD (men aged <55 years and women aged <60 years) and history of high LDL-C (≥5 mmol/L) levels without secondary causes of hypercholesterolemia. Clinical probability of FH was estimated, and genetic testing of FH was carried out in 80 patients with informed consent. Of the 80 patients with premature CAD and history of high LDL-C levels, 70% were men; the age at diagnosis of CAD for male and female patients was 48 and 53 years, respectively. In total, 58 (73%) patients had probable (n = 54) or definite (n = 4) FH based on Dutch Lipid Clinic Network criteria. A pathogenic variant of FH was found in five (6%) patients. Prevalence of the genetically verified FH was 1:16. The FH variant was found in 75% of patients with definite FH. The prevalence of genetically verified FH was 1:16 among patients with premature CAD and elevated LDL-C level, which is 38 times higher than the estimated prevalence of 1:600 in the general Finnish population.

Reproduction cycle, trematode parasitism and growth of freshwater mussel Anodonta anatina (Bivalvia: Unionidae)

Anodonta anatina, a widely distributed Eurasian freshwater mussel, has dramatically declined and listed as endangered species in IUCN Red List in some parts of the Europe. To better understand its basic biology and possible sex-dependent effects of parasitism on reproduction, we investigated the reproductive traits, trematode parasitism and growth between November 2020 and October 2021. Our data from a Finnish population indicates male-biased sex ratio and the gonadal development lasting throughout the year with a bradytictic brooding pattern. Gonadosomatic index of both sexes peaked in May and declined in June. Mature oocytes were smaller sized than those of previously studied unionids, fecundity was fairly low, and the maximum predicted lifespan was 14 years. Gonads were infected with digenean trematode parasites, Rhipidocotyle campanula being the dominant species. Interestingly, trematode infection rate was higher in females than in males. In July, when the water temperature reached its annual maximum, the trematode prevalence also peaked, which was accompanied with 16% of mussels being sterile. The trematode parasitism was thus negatively associated with reproduction, that might become even more affected if parasitism increases along with the predicted climate warming, which should be considered in possible future conservation and aquaculture efforts of this species.

Causes of fatal traumatic brain injury in Finland.

The phenotype of patients who suffer fatal traumatic brain injury (TBI) is poorly characterized. The authors examined the external causes, contributing diseases, and preinjury medication in adult patients with fatal TBI in a nationwide Finnish cohort. Deaths caused by TBIs in Finland were examined among decedents aged ≥ 16 years during 2005-2020 from the national Cause of Death Registry. Usage of prescription medications prior to TBI was studied using medication purchase data from the Social Insurance Institution of Finland. The cohort consisted of 71,488,347 person-years, 821,259 total deaths, and 14,630 TBI-related deaths during 2005-2020, of which 67% (n = 9792) occurred in men. Women were older than men among those who suffered TBI-related death (mean age 77.2 ± 17.1 vs 64.5 ± 19.5 years, p < 0.0001). The overall crude incidence rate of fatal TBIs was 20.5/100,000 person-years (28.1/100,000 in men and 13.2/100,000 in women). TBI was the cause of death in 1.8% of all deaths in the Finnish population during the study years, but in patients aged 16-19 years, TBIs caused more than 17% of all deaths. The most common external cause of fatal TBI was a fall (70%), followed by poisoning or toxic effects (20%) and violence or self-harm (15%) overall. In men, the order of the most common causes of fatal TBI was similar to overall results (64%, 25%, and 19%, respectively), while in women, the most common cause was a fall (82%), followed by complications in healthcare (10%) and poisoning or toxic effects (9%). Cardiovascular diseases, psychiatric diseases, and infections were the most common diseases contributing to death. Blood pressure (lowering) medications were the most common type of medications used before fatal TBI. CNS medications were the second most common medication group. In the context of fatal TBI in Europe, Finland remains at the upper end of fatal TBI incidence. TBI is a common cause of death in young adults, whereas the incidence of fatal TBI becomes increasingly higher with age in Finland. Cardiovascular diseases and psychiatric conditions were the most common diseases related to death, with opposite age trends. Healthcare facility complications were an alarmingly common cause of death in women with fatal TBI.

In situ fixation of slipped capital femoral epiphysis carries a greater than 40% risk of later total hip arthroplasty during a long-term follow-up.

We aimed to assess the cumulative risk of total hip arthroplasty (THA) from in situ fixation for slipped capital femoral epiphysis (SCFE) after a follow-up of almost 50 years. In this study, 138 patients with 172 affected hips treated with in situ fixation were evaluated retrospectively. A total of 97 patients (70%) were male and the mean age was 13.6 years (SD 2.1); 35 patients (25%) had a bilateral disease. The median follow-up time was 49 years (interquartile range 43 to 55). Basic demographic, stability, and surgical details were obtained from patient records. Preoperative radiographs (slip angle; SA) were measured, and data on THA was gathered from the Finnish National Arthroplasty Register. The preoperative SA was a mean of 39° (SD 19°). At follow-up, 56 of the patients had undergone THA for a hip previously fixed in situ for SCFE (41%) and 64 of all affected hips had been replaced (37%). Kaplan-Meier analysis gave a median prosthesis-free postoperative survival of 55 years (95% confidence interval (CI) 45 to 64) for the affected hips. In a multivariate analysis, female patients had a two-fold risk for THA (hazard ratio (HR) 2.42 (95% CI 1.16 to 5.07)) and a greater preoperative SA increased the risk of THA (HR 1.03 for every increment of 1° (95% CI 1.01 to 1.05)), while patient age at surgery, slip laterality, stability of slip, or diagnostic delay did not have a statistically significant effect on the risk of THA. SCFE treated primarily with in situ fixation may lead to THA in more than 40% of affected hips at a near 50-year follow-up. This risk is approximately 15-times the reported lifetime risk in the Finnish general population. Female sex and increasing preoperative SA significantly predicted higher risk of THA.

Impact of genetic risk in multidomain lifestyle preventive interventions

AbstractBackgroundInteractions between genetic and lifestyle‐related risk factors for dementia have been investigated mainly in observational studies, with conflicting results. Less is known about whether genetic risk factors for dementia (not just APOE4 allele but also polygenic risk beyond APOE4) have an impact on the effects of multidomain lifestyle preventive interventions on cognition. Although there is overlap between risk factors for dementia and e.g. cardiovascular diseases (CVD), it is unclear if CVD genetic risk may also have an impact on potential intervention benefits.MethodThe FINGER randomized controlled trial included 1260 participants aged 60‐77 years and at risk for dementia from the general Finnish population. Cognition improved more during 2 years in the multidomain lifestyle intervention (diet, exercise, cognitive training, social activities and cardiovascular risk monitoring) compared with control (regular health advice) group. Genetic risk scores for Alzheimer’s disease (AD‐GRS, excluding APOE) and CVD‐GRS were selected based on existing literature, and calculated using GWAS data from FINGER participants.ResultPrevious findings indicated that the FINGER intervention had clear cognitive benefits among APOE4 carriers. Preliminary results suggested a less straightforward impact of AD‐GRS, especially after adjustment for APOE4. There seemed to be a pattern of more intervention‐related cognitive benefit among participants with lower compared with higher CVD‐GRS.ConclusionAPOE4, AD‐GRS and CVD‐GRS may have different impact on the cognitive benefits of multidomain lifestyle interventions for dementia prevention. Ongoing World‐Wide FINGERS trials in populations with a variety of genetic profiles will create opportunities for more detailed investigation of genetic‐lifestyle interactions in the context of preventive interventions.

Recalling Biobank Participants to Clinical Study of Alzheimer’s Disease – FinnGen Pilot Study

AbstractBackgroundPopulation‐based biobanks that comprehensively ascertain health and genetic data hold promise to facilitate identification of Alzheimer’s disease (AD) trial participants. We conducted a pilot study in individuals with mild impairment in cognition or AD to assess the feasibility of recalling biobank participants. We also tested the utility of computer‐ and telephone‐based cognitive assessments as cost‐effective alternatives to in‐person neuropsychological testing and investigated plasma‐based biomarkers.MethodsWe utilized FinnGen, a large population‐based biobank study of up to 500,000 participants representing almost 10% of the Finnish population. Single‐center cross‐sectional study included individuals with ICD‐10 codes for AD (G30) and mild cognitive disorder (MCD; F06.7). Dementia screening instruments were in‐person Mini‐Mental State Examination (MMSE) and telephone interview for dementia (TELE). Episodic memory was assessed with three trial word list tasks in three formats; in‐person, with web‐based tool and with the modified Telephone Interview for Cognitive Status including three learning trials. Each of these yielded immediate and delayed free recall measures. Blood samples were collected to determine plasma‐based biomarkers: amyloid beta (Aβ)1‐40 to Aβ1‐42 ratio, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL) and phosphorylated‐tau181 (pTau‐181).ResultsA total of 78% (110/140) of a pre‐specified FinnGen sub‐cohort were successfully reached. Of those, 39% (43/110) were willing to participate and 19% (N = 27, mean age = 72y, 13 women) completed the study. FinnGen and hospital records largely matched. For 8/12, MCD was due to other reasons than early AD. MMSE and TELE correlated .818 (p&lt; .001). Immediate and delayed recall measures correlated across three formats: from .584 to .679 (p’s&lt;.003) and from .250 to .424 (p’s: .031 ‐ .218), respectively. AD group had higher levels of GFAP (p = .002) and pTau‐181 (p = .020). TELE was negatively correlated with GFAP (p = .011), NfL (p = .001) and pTau‐181 (p = .006). Moreover, p‐Tau181 had negative correlations with episodic memory measures (all r’s&lt; ‐.202) with telephone‐administered immediate recall reaching statistical significance (r = ‐.394, p = .042).ConclusionsInformative, customized clinical recall studies from FinnGen are feasible. Remote testing is a cost‐effective approach in recall studies. Next phase of our study aims to invite cognitively unimpaired FinnGen participants for screening of high AD risk individuals.

Physical appearance and elections: An inequality perspective

AbstractA consensus seems to exist around physically attractive candidates winning elections more often. Unfortunately, we have limited understanding of how voters assess candidates with socioeconomically (dis)advantageous physical appearances. To bridge this gap, we studied the electoral consequences of candidates looking upper class, middle class, or working class. Using official electoral data for the 2017 Finnish municipal elections and a novel data set based on a representative sample of the Finnish population (N = 7,920), we found that Finnish citizens systematically vote for candidates who look like they have (and do have) upper‐class occupations. Furthermore, the data strongly suggest that a systematic electoral penalty exists, particularly for female candidates who look like they have (and do have) working‐class occupations.

Estimating the Population-Based Prevalence of Congenital Thrombotic Thrombocytopenic Purpura Using Large-Scale Sequencing Data

Introduction Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder caused by severe ADAMTS13 deficiency. This severe deficiency (&amp;lt;10%) is classified into two forms of acquired or hereditary TTP. Acquired TTP is either due to circulating autoantibodies inhibiting ADAMTS13 activity or increasing its clearance, whereas congenital TTP results from homozygous or compound heterozygous ADAMTS13 mutations (cTTP, Upshaw-Schulman syndrome). Because of ADAMTS13 defects, an abnormal amount of ultra-large von Willebrand factor multimers is concentrated, resulting in the formation of platelet-rich microthrombi in the circulation. Given that the true prevalence of cTTP is not established, we sought to leverage the availability of exome or genome sequences of very large numbers of individuals (genome Aggregation Database, gnomAD) to estimate the worldwide and within-population prevalence of cTTP. We also aimed to examine the global mutational landscape of ADAMTS13. Methods Exome and genome sequencing data of 141,456 subjects of gnomAD were extracted and analyzed for ADAMTS13. We comprehensively reviewed literature to identify all ADAMTS13 variants that have been associated with cTTP so far. In addition, all variants reported to be associated with cTTP in HGMD and/or LOVD datasets were included. Finally, we searched for ADAMTS13 variants in ClinVar that have been classified as “pathogenic” or “likely pathogenic”. The following gnomAD variants were considered pathogenic: variants associated with cTTP in HGMD/LOVD; nonsense, frameshift, inframe deletion/insertion variants; splicing variants affecting the first/last two intronic nucleotides; splicing variants affecting the first/last eight intronic nucleotides predicted deleterious by 4 different in silico tools; missense variants predicted deleterious by 7 different in silico tools. Using the frequencies of known or predicted pathogenic variants in ADAMTS13 of the gnomAD population (n= 141,456), we estimated the prevalence of individuals homozygous or compound heterozygous for cTTP (assuming Hardy-Weinberg equilibrium). Results Following quality controls and removing variants with no clear association with cTTP, we found that 302 different ADAMTS13 variants have been so far reported to cause cTTP in the literature, HGMD and LOVD as well as ClinVar. We then collected high-quality data from gnomAD population including 141,456 subjects with different ethnicities: 12,487 Africans/African Americans, 17,720 Latinos/Admixed Americans, 5,185 Ashkenazi Jewish, 9,977 East Asians, 12,562 Finnish Europeans, 64,603 non-Finnish Europeans, 15,308 South Asians, and 3,614 persons without an assigned ethnicity. We identified a total number of 2212 variants within ADAMTS13 among 282,912 alleles analyzed in the gnomAD population. Of these, following a conservative approach, 250 different variants were pathogenic; 83 reported to be associated with cTTP and 167 predicted to be pathogenic. Among a maximum number of 282912 alleles analyzed, 2166 alleles were affected by novel or reported variants. Of which, 53% of the affected alleles were due to known pathogenic variants and the remaining 47% were due to novel predicted variants. Considering all pathogenic variants (n=250) and only those reported (n=83), we estimated an overall cTTP prevalence of 17 and 59 individuals per million people, respectively (Table 1). Considering reported variants only, the highest prevalence of cTTP was estimated in Europeans and Finnish population (30 and 26 per 10 6), followed by Latinos/Admixed Americans (14 per 10 6) and Africans/African Americans (6 per 10 6). East and South Asian ethnicities had a lower estimated prevalence of 4 and 3 per 10 6, respectively. Ashkenazi Jewish population had the lowest estimated prevalence of cTTP (0.6 per 10 6) among all populations (Table 1). Conclusion We have attempted to estimate the worldwide and within-population prevalence of cTTP using available genome/exome sequencing data of 141,456 individuals. Our results reveal that putative disease alleles and cTTP-associated variants are more prevalent than expected and the true cTTP prevalence is more than ten times higher than was reported. This finding suggests that a large number of patients might be undiagnosed. We also established the mutational burden of ADAMTS13 by identifying 167 novel variants in addition to the 302 previously reported.