We study the predictive power and associations of several psychopathology and temperament scales with respect to schizophrenia and other psychotic disorders. Measures of psychopathology (Physical and Social Anhedonia Scales, Perceptual Aberration Scale, Hypomanic Personality Scale, Bipolar II Scale, and Schizoidia Scale) and the Temperament and Character Inventory were included in the 31-year follow-up of the prospective Northern Finland 1966 birth cohort (N = 4926). The Perceptual Aberration Scale was the best scale for concurrent validity in psychoses, and also the best psychopathology scale in terms of discriminant validity. Participants scoring high in hypomanic personality were at the highest risk for developing psychosis during the 11-year follow-up. Harm avoidance was a dominant temperament dimension in individuals with psychosis compared with participants without psychiatric diagnoses. These scales are useful as vulnerability markers in studying psychoses.
Population-based research on vitamin D has increased dramatically in recent years. Such studies are typically reliant on assay procedures to measure reliable and comparable levels of 25-hydroxyvitamin D [25(OH)D] concentrations.
Concentrations of 25(OH)D3 and 25(OH)D2 were measured using LC-MS/MS in 5,915 participants (aged 31?years) of Northern Finland Birth Cohort 1966. Blood samples were assayed in batches over a course of 18?months. As anomalies were present in the measurements, 200 samples were reassayed using Diasorin RIA. Agreement between measurements was assessed by Passing-Bablok regression and limits of agreement (LoA). To harmonize LC-MS/MS with Diasorin RIA measurements, formulae were derived from the LoA.
Concentrations measured by LC-MS/MS were much higher than those measured by Diasorin RIA, with a mean difference of 12.9?ng/ml. Constant variation was evident between batch measurements after log transformation. Statistical formula was applied separately for each batch of LC-MS/MS measurements, enabling us to remove both the constant and proportional bias that was evident prior to the transformation.
Despite the introduction of schemes/programs to improve accuracy of assays to measure 25(OH)D, significant differences can still happen. In these instances, methods to harmonize measurements based on a relatively small number of replicates can be successfully applied to establish confidence and to enable between-study comparisons.
Simple screening questionnaires for major psychiatric disorders are needed for epidemiological research and clinical work. We describe the characteristics of the Hopkins Symptom Checklist-25 (HSCL-25) as a screening instrument in a two-phase epidemiological survey using the Structured Clinical Interview for DSM-III-R (SCID) as a diagnostic tool. The material consisted of 1609 subjects aged 31 years who were asked to participate in a health survey. The invitation included the HSCL-25 questionnaire. All "screen-positive" (HSCL-25 mean>/=1.55) subjects and every tenth "screen-negative" subject were invited to participate in the SCID interview. The sensitivity of the HSCL-25 for any present DSM-III-R axis-I psychiatric disorder was 48%. The specificity was 87%. The sensitivity of cases with comorbid psychiatric disorders was 100%. The HSCL-25 is a moderate instrument for screening with present axis-I DSM-III-R psychiatric disorders in a young adult population. It can be recommended for screening of psychiatric disorders.
Stability Selection, which combines penalized regression with subsampling, is a promising algorithm to perform variable selection in ultra high dimension. This work is motivated by its evaluation in the context of genome-wide association studies (GWAS). One critical aspect for its use lies in the choice of a decision rule that accounts for the massive number of comparisons realised. The current decision rule relies on the control of the Family Wise Error Rate (FWER) by means of an upper bound derived theoretically. Alternatively, we propose to set the detection threshold according to the more liberal false discovery rate (FDR) criterion. The procedure we propose for its estimation relies on permutations. This procedure is evaluated by simulations according to several scenarios mimicking various correlation structures of genetic data and is compared to the original FWER upper bound. The proposed procedure is shown to be less conservative, and able to pick up more true signals than the FWER upper bound. Finally, the proposed methodology is illustrated on a GWAS analysis of a lipid phenotype (high-density lipoproteins, HDL) in the Northern Finland Birth Cohort.
Gestation is a crucial timepoint in human development. Deviation from a term gestational age correlates with both acute and long-term adverse health effects for the child. Both being born preterm and post-term, that is, having short and long gestational ages, are heritable and influenced by the prenatal and perinatal environment. Despite the obvious heritable component, specific genetic influences underlying differences in gestational age are poorly understood.
We investigated the genetic architecture of gestational age in 9141 individuals, including 1167 born post-term, across two Northern Finland cohorts born in 1966 or 1986.
Here we identify one globally significant intronic genetic variant within the ADAMTS13 gene that is associated with prolonged gestation (p=4.85×10-8). Additional variants that reached suggestive levels of significance were identified within introns at the ARGHAP42 and TKT genes, and in the upstream (5') intergenic regions of the B3GALT5 and SSBP2 genes. The variants near the ADAMTS13, B3GALT5, SSBP2 and TKT loci are linked to alterations in gene expression levels (cis-eQTLs). Luciferase assays confirmed the allele specific enhancer activity for the BGALT5 and TKT loci.
Our findings provide the first evidence of a specific genetic influence associated with prolonged gestation. This study forms a foundation for a better understanding of the genetic and long-term health risks faced by induced and post-term individuals. The long-term risks for induced individuals who have a previously overlooked post-term potential may be a major issue for current health providers.
Genome-wide association studies (GWAS) of longitudinal birth cohorts enable joint investigation of environmental and genetic influences on complex traits. We report GWAS results for nine quantitative metabolic traits (triglycerides, high-density lipoprotein, low-density lipoprotein, glucose, insulin, C-reactive protein, body mass index, and systolic and diastolic blood pressure) in the Northern Finland Birth Cohort 1966 (NFBC1966), drawn from the most genetically isolated Finnish regions. We replicate most previously reported associations for these traits and identify nine new associations, several of which highlight genes with metabolic functions: high-density lipoprotein with NR1H3 (LXRA), low-density lipoprotein with AR and FADS1-FADS2, glucose with MTNR1B, and insulin with PANK1. Two of these new associations emerged after adjustment of results for body mass index. Gene-environment interaction analyses suggested additional associations, which will require validation in larger samples. The currently identified loci, together with quantified environmental exposures, explain little of the trait variation in NFBC1966. The association observed between low-density lipoprotein and an infrequent variant in AR suggests the potential of such a cohort for identifying associations with both common, low-impact and rarer, high-impact quantitative trait loci.
A cross-sectional magnetic resonance imaging (MRI) study.
We investigated the association among Modic changes, Schmorl's nodes, spondylolytic defects, high-intensity zone lesions, radial tears, herniations, and low back symptom severity.
Disc degeneration is associated with low back pain in early adulthood, but the associations between other MRI findings and low back pain are not well known.
Questionnaire data and MRI scans (1.5-T) were available for 554 subjects derived from a birth cohort at 21 years of age. Data on low back pain and back-related functional limitations at 18, 19, and 21 years of age were used for clustering of subjects, using latent class analysis. We used logistic regression with adjustment for the degree of disc degeneration to evaluate the associations between specific imaging findings and low back symptom severity.
The prevalence of herniations was 20%, Schmorl's nodes 17%, radial tears 9.9%, high-intensity zone lesions 3.2%, spondylolytic defects 5.8%, and Modic changes 0.7%. Latent class analysis produced 5 clusters: "Always Painful" (n = 65) meant painful at all time points and "Recent Onset Pain" (n = 56) meant increasing symptom severity, whereas subjects in the "Moderately Painful" (n = 73), "Minor Pain" (n = 193), and "No Pain" (n = 167) clusters had fewer symptoms. Compared with the "No Pain" cluster, Schmorl's nodes were more likely to occur in the "Always Painful" cluster (P = 0.017) and herniations in the 3 most painful clusters (P