Danish population based study of familial epilepsy and childhood cancer.

Results from studies investigating the association between maternal or child epilepsy, use of anticonvulsants in pregnancy, and childhood cancer are inconsistent and at times contradictory. Linking Danish national databases, we obtained epilepsy and childhood cancer diagnoses, and anticonvulsant use data. We estimated adjusted odds ratios of all or specific childhood cancers in relation to maternal or child epilepsy and anticonvulsant therapies using conditional logistic regression. Maternal epilepsy was positively associated with all childhood cancers in offspring, specifically, with acute lymphoblastic leukemia (Odds Ratio (OR) = 1.68, 95% Confidence Interval (CI) = 1.16, 2.43) and Wilms tumor (OR = 2.13, 95% CI = 0.97, 4.68). When considering maternal ever (lifetime) ingestion of anticonvulsants, a positive association was found with all cancers (OR = 1.14, 95% CI = 1.00, 1.30), and central nervous system tumors (CNS) (OR = 1.36, 95% CI = 1.04, 1.76) as well as neuroblastoma (OR = 1.76, 95% CI = 1.06, 2.90) among offspring. Maternal anticonvulsant use before or during the index pregnancy was related to CNS tumors in offspring (OR = 1.99, 95% CI = 0.99, 4.00).

Genetic prediction of 33 blood group phenotypes using an existing genotype dataset.

BACKGROUND: Accurate blood type data are essential for blood bank management, but due to costs, few of 43 blood group systems are routinely determined in Danish blood banks. However, a more comprehensive dataset of blood types is useful in scenarios such as rare blood type allocation. We aimed to investigate the viability and accuracy of predicting blood types by leveraging an existing dataset of imputed genotypes for two cohorts of approximately 90,000 each (Danish Blood Donor Study and Copenhagen Biobank) and present a more comprehensive overview of blood types for our Danish donor cohort. STUDY DESIGN AND METHODS: Blood types were predicted from genome array data using known variant determinants. Prediction accuracy was confirmed by comparing with preexisting serological blood types. The Vel blood group was used to test the viability of using genetic prediction to narrow down the list of candidate donors with rare blood types. RESULTS: Predicted phenotypes showed a high balanced accuracy >99.5% in most cases: A, B, C/c, Coa /Cob , Doa /Dob , E/e, Jka /Jkb , Kna /Knb , Kpa /Kpb , M/N, S/s, Sda , Se, and Yta /Ytb , while some performed slightly worse: Fya /Fyb , K/k, Lua /Lub , and Vel ~99%-98% and CW and P1 ~96%. Genetic prediction identified 70 potential Vel negatives in our cohort, 64 of whom were confirmed correct using polymerase chain reaction (negative predictive value: 91.5%). DISCUSSION: High genetic prediction accuracy in most blood groups demonstrated the viability of generating blood types using preexisting genotype data at no cost and successfully narrowed the pool of potential individuals with the rare Vel-negative phenotype from 180,000 to 70.

Forensic sex estimation using the vertebrae: an evaluation on two European populations.

Sex estimation is one of the primary steps for constructing the biological profile of skeletal remains leading to their identification in the forensic context. While the pelvis is the most sex diagnostic bone, the cranium and other post-cranial elements have been extensively studied. Earlier research has also focused on the vertebral column with varying results regarding its sex classification accuracy as well as the underlying population specificity. The present study focuses on three easily identifiable vertebrae, namely T1, T12, and L1, and utilizes two modern European populations, a Greek and a Danish, to evaluate their forensic utility in sex identification. To this end, 865 vertebrae from 339 individuals have been analyzed for sexual dimorphism by further evaluating the effects of age-at-death and population affinity on its expression. Our results show that T1 is the best sex diagnostic vertebra for both populations reaching cross-validated accuracy of almost 90%, while age-at-death has limited effect on its sexual dimorphism. On the contrary, T12 and L1 produced varying results ranging from 75 to 83% accuracy with the Greek population exhibiting distinctively more pronounced sexual dimorphism. Additionally, age-at-death had significant effect on sexual dimorphism of T12 and L1 and especially in the Greek female and Danish male groups. Our results on inter-population comparison suggest that vertebral sex discriminant functions, and especially those utilizing multiple measurements, are highly population specific and optimally suitable only for their targeted population. An open-source software tool to facilitate classifying new cases based on our results is made freely available to forensic researchers.

Danish Population Based Study of Familial Epilepsy and Childhood Cancer.

Objective: Results from studies investigating the association between maternal or child epilepsy, use of anticonvulsants in pregnancy, and childhood cancer are inconsistent and at times contradictory. Methods: Linking Danish national databases, we obtained epilepsy and childhood cancer diagnoses, and anticonvulsant use data. We estimated adjusted odds ratios of all or specific childhood cancers in relation to maternal or child epilepsy and anticonvulsant therapies using conditional logistic regression. Results: Maternal epilepsy was positively associated with all childhood cancers in offspring, specifically, with acute lymphoblastic leukemia (Odds Ratio (OR) = 1.68, 95% Confidence Interval (CI) = 1.16, 2.43) and Wilms tumor (OR = 2.13, 95%CI = 0.97, 4.68). When considering maternal ever (lifetime) ingestion of anticonvulsants, a positive association was found with all cancers (OR = 1.15, 95%CI = 1.01, 1.31), and central nervous system tumors (OR = 1.32, 95%CI = 1.03, 1.69) as well as neuroblastoma (OR = 2.05, 95%CI = 1.29, 3.28) among offspring. Maternal anticonvulsant use before or during the index pregnancy was related to CNS tumors in offspring (OR = 1.78, 95%CI = 0.99, 3.21), however the confidence interval included the null. Significance: Maternal use of certain anticonvulsant medications may be a risk factor for cancer in offspring. Medical providers may need to consider what type of treatments to prescribe to pregnant mothers with epilepsy.

The role of early-life family composition and parental socio-economic status as risk factors for obsessive-compulsive disorder in a Danish national cohort.

Research on early-life family environment on obsessive-compulsive disorder (OCD) risk is limited, and sex differences have not been sufficiently studied. We investigated early-life family composition and parental socio-economic status (SES) as OCD risk factors while stratifying for sex in a sample of 1,154,067 individuals from the Danish population (7550 of whom had OCD). Data on early-life family composition (birth order, number of siblings, number of parents in household at proband age 6), parental SES at age 6 (parental income, occupation, and education level), history of parental psychiatric illness, and parental age at birth on OCD risk (i.e., an ICD-10 diagnosis of F42.x) were obtained from Danish population registers. Survival analyses using Cox regression were performed with age as the underlying time variable. Analyses were adjusted for calendar time, and differential effect by sex was tested for exposures. We found that birth order and advanced maternal age were risk factors for OCD in males, and being an only child was associated with increased OCD risk in both sexes. Early childhood SES variables including parental education, occupation, and income were associated with OCD risk, and these effects were more pronounced in females. Significant interaction effects for parental education/occupation and the presence of non-OCD psychiatric diagnoses in the proband also emerged. Our results suggest that early-life SES and family composition may be important risk factors for OCD, and heterogeneity in OCD cases in terms of psychiatric comorbidities, as well as sex differences should be carefully examined in relation to risk factors.

Associations between obesity and mental distress in late midlife: results from a large Danish community sample.

BACKGROUND: To examine associations of Body mass Index (BMI) and mental distress in late midlife in a large Danish community sample and to investigate the effect of socio-demographic factors. METHODS: The study sample comprised 3613 Danish men and 1673 women aged 49-63 years from the Copenhagen Ageing and Midlife Biobank (CAMB) with complete information on measured BMI, severity of mental symptoms assessed by the Symptom Check-List' (SCL-90), and socio-demographic factors including sex, age, occupational social class, and educational duration. Linear and logistic regression were used to evaluate associations between BMI category and SCL-90. RESULTS: Unadjusted SCL-90 subscale scores differed significantly across BMI categories (p < 0.001) among both men and women with more mental distress in the underweight, obese and severely obese BMI categories except for the anxiety scale which was not associated with BMI category in women. In the adjusted analyses, all symptom scales remained significantly associated with BMI among men after adjusting for socio-demographic factors while only associations with somatization and depression scales remained significant for women.. When SCL-90 case status was applied as an outcome, significant unadjusted associations with BMI category were observed for somatization (p < 0.001), depression (p = 0.026) and the General Severity Index (p = 0.002) among men and somatization (p = 0.002) among women. Furthermore, somatization case-status was significantly predicted by BMI category (p < 0.001) in men after adjusting for socio-demographic factors. CONCLUSION: Results indicate more mental distress among underweight, obese and severely obese men and women after adjusting for socio-demographic factors. Furthermore, obese men have higher risk of reporting clinically relevant symptoms of somatization independently of socio-demographic factors.

Relative validity and reproducibility of a food frequency questionnaire to assess dietary fiber intake in Danish adults.

BACKGROUND: Differences in habitual dietary fiber intake may modify effects of dietary fiber interventions, thus measurement of habitual dietary fiber intake is relevant to apply in intervention studies on fiber-rich foods, and food frequency questionnaire (FFQ) is a commonly used method. Rye bread is the major contributor of dietary fiber in the Danish population, and a nation-specific FFQ is therefore needed. OBJECTIVE: The aim of this study was to assess the relative validity and reproducibility of a self-administered quantitative FFQ designed to assess total dietary fiber intake among Danish adults. DESIGN: In order to assess the relative validity of the FFQ, a total of 125 participants completed both a 7-day weighed dietary recording (DR) and an FFQ consisting of 60 questions. To evaluate the reproducibility of the FFQ, a sub-group of 12 participants subsequently completed an FFQ approximately 6 months later. RESULTS: Estimates of mean dietary fiber intake were 24.9±9.8 and 28.1±9.4 g/day when applying the FFQ and DR, respectively, where FFQ estimates were ~12% lower (p<0.001). Pearson's correlation coefficient between the estimated dietary fiber intake of the two methods was r=0.63 (p<0.001), and 62% of the participants were grouped into the same tertile of intake according to the two methods. The estimates of mean dietary intake of first and second FFQ were very similar (22.2±4.0 and 23.3±4.1 g/day, respectively, p=0.42) and showed a correlation of r=0.95 (95% CI 0.83-0.99). CONCLUSION: The developed FFQ showed moderate underestimation of dietary fiber intake (g/day), adequate ranking of subjects according to their dietary fiber intake, and good reproducibility. The FFQ is therefore believed to be a valuable tool for epidemiology and screening in human interventions, where intake of dietary fibers is of specific interest.