Contribution of Alcohol and Nicotine Dependence to the Prevalence of Depressed Mood in Different Ethnic Groups in The Netherlands: The HELIUS Study

Abstract

Objective: Ethnic minorities report different levels of drinking and smoking and higher rates of depression compared to native populations. In this study we aimed to investigate in six ethnic groups whether tobacco and alcohol use were associated with depressive symptoms, which are more prevalent in ethnic minorities.

Methods: Cross-sectional data from the multi-ethnic Healthy Life in an Urban Setting (HELIUS) study sample (N?=?22,471) was used, comprising 4,580 native Dutch participants which were compared with participants from five ethnic minority groups (3,259 South Asian Surinamese, 4,292 African Surinamese, 2,262 Ghanaian, 3,891 Turkish, and 4,187 Moroccan).

Results: Alcohol misuse was positively associated with depressed mood in all ethnic groups except for the Dutch and the Ghanaians. Nicotine dependence was positively associated with depressed mood in all ethnic groups except for the Ghanaian group.

Conclusions: Alcohol misuse and nicotine dependence were significantly associated with depressed mood in most but not all ethnic groups and especially in men. However, across all groups the contribution of alcohol misuse and nicotine dependence to depressed mood was small. Prospective multi-ethnic studies should confirm whether the relations are causal and elucidate their direction.     

No evidence that common genetic risk variation is shared between schizophrenia and autism

The similarity between aspects of the clinical presentation of schizophrenia and autism spectrum disorders (ASD) suggests that elements of the biological etiology may also be shared between these two disorders. Recently, an increasing number of rare, mostly structural genetic variants are reported to increase the risk of both schizophrenia and ASD. We hypothesized that given this evidence for a shared genetic background based on rare genetic variants, common risk alleles may also be shared between ASD and schizophrenia. To test this hypothesis, the polygenic score, which summarizes the collective effect of a large number of common risk alleles, was used. We examined whether the polygenic score derived from a schizophrenia case–control dataset, previously reported by Purcell et al., was able to differentiate ASD cases from controls. The results demonstrate that the schizophrenia‐derived polygenic score is not different between ASD cases and controls, indicating that there is no important sharing of common risk alleles between the two neuropsychiatric disorders. Possibly, common risk alleles are less important in ASD in comparison to their more prominent role in schizophrenia and bipolar disorders. These findings provide important novel insights into shared and distinct elements of the genetic architecture of autism and schizophrenia. © 2012 Wiley Periodicals, Inc.     

High reliability of an algorithm for choice of implants in hip fracture patients

Purpose

Hip fracture treatment is controversial, with high complication rates. An algorithm for hip fracture surgery has shown reduced reoperation rates, but choice of implant is based on the commonly used fracture classifications, which were previously evaluated to be unreliable. The purpose of this study was to investigate the reliability of the algorithm.

Methods

From two hospitals, four observers (orthopaedic consultant, fellow, resident and intern) used the algorithm to classify into 15 hip fracture types [Garden type I–IV femoral neck including posterior tilt, vertical femoral neck, basocervical and Arbeitsgemeinschaft für Osteosynthesefragen (AO)-31 A1.1 to A3.3 trochanteric fractures] and to choose between five surgical procedures [parallel implants, prosthesis, two-or four-hole sliding hip screw (SHS) and intermedullary (IM) nail]. After individual assessment, each hospital made a consensus decision. Observations were performed twice, ten weeks apart, on pelvic, anteroposterior (AP) and axial X-rays from 100 consecutive patients.

Results

For fracture classification, mean kappa values were 0.60 for intra and 0.62 for interobserver variation, with interobserver variation between hospitals at 0.65. For posterior tilt, mean intraclass correlation coefficient was 0.91 for intra and 0.87 for interobserver variation. For choice of implant type, mean kappa values were 0.86 for both intra and interobserver variation. The two hospital consensus decisions chose same implant in 91 of 100 patients, giving a kappa value at 0.88.

Conclusion

Although hip fracture classification confirmed to be somewhat unreliable in this study, posterior tilt measurement and subsequent choice of implant type by the algorithm was found to be reliable, which opens up the possibility for a more standardized treatment of hip fracture patients between hospitals.     

Intraspecific phylogenetic analysis of Siberian woolly mammoths using complete mitochondrial genomes

We report five new complete mitochondrial DNA (mtDNA) genomes of Siberian woolly mammoth (Mammuthus primigenius), sequenced with up to 73-fold coverage from DNA extracted from hair shaft material. Three of the sequences present the first complete mtDNA genomes of mammoth clade II. Analysis of these and 13 recently published mtDNA genomes demonstrates the existence of two apparently sympatric mtDNA clades that exhibit high interclade divergence. The analytical power afforded by the analysis of the complete mtDNA genomes reveals a surprisingly ancient coalescence age of the two clades, approximately 1-2 million years, depending on the calibration technique. Furthermore, statistical analysis of the temporal distribution of the (14)C ages of these and previously identified members of the two mammoth clades suggests that clade II went extinct before clade I. Modeling of protein structures failed to indicate any important functional difference between genomes belonging to the two clades, suggesting that the loss of clade II more likely is due to genetic drift than a selective sweep.     

Preoperative TruCulture® whole blood cytokine response predicts post-operative inflammation in pancreaticoduodenectomy patients—A pilot cohort study

Major surgery is associated with substantial morbidity and mortality with early post-operative adverse events (POAE) occurring in 30% of patients within the first 30 days. The underlying pathogenesis is multifactorial, including immune dysfunction and increased inflammatory response to surgery. We investigated preoperative immune function by the TruCulture® whole blood technique in a cohort of patients undergoing pancreaticoduodenectomy (PD), hypothesizing that patients developing inflammatory POAE defined as leucocytosis, fever or high (above median) area under the curve (AUC) C-reactive protein (CRP) the first post-operative week would display perturbed preoperative immune function. Sixty-two adult patients were screened, 30 included and 11 excluded post-inclusion due to other surgical procedures than PD and post-operative complications directly attributed to surgery, leaving 19 patients for analysis of preoperative immune function. Patients developing leucocytosis (n = 5, 26%) had lower Toll-like receptor (TLR)-3–stimulated IL-12p40 and higher Candida Albicans (TLR1/2/4/6, Dectin-1)-stimulated TNF-α, compared to patients without leucocytosis (all P < .05). Patients developing fever (n = 7, 37%) had lower TLR7/8-stimulated IFN-γ and patients with high AUC CRP (n = 9, 47%) had lower TLR3-stimulated IFN-γ and IL-6 and lower TLR7/8-stimulated IL-10 (all P < .05), compared to patients without fever or low CRP, respectively. In conclusion, patients with inflammatory POAE displayed lower preoperative stimulated IL-12p40, IFN-γ, IL-6 and IL-10 and higher TNF-α response, compared to patients without inflammatory POAE. This finding suggests that TruCulture is a feasible immunologic screening tool in surgical patients, with a potential for preoperative identification of patients at increased risk for inflammatory POAE, allowing for risk-based intervention trials.     

Genome-wide nucleosome map and cytosine methylation levels of an ancient human genome

Epigenetic information is available from contemporary organisms, but is difficult to track back in evolutionary time. Here, we show that genome-wide epigenetic information can be gathered directly from next-generation sequence reads of DNA isolated from ancient remains. Using the genome sequence data generated from hair shafts of a 4000-yr-old Paleo-Eskimo belonging to the Saqqaq culture, we generate the first ancient nucleosome map coupled with a genome-wide survey of cytosine methylation levels. The validity of both nucleosome map and methylation levels were confirmed by the recovery of the expected signals at promoter regions, exon/intron boundaries, and CTCF sites. The top-scoring nucleosome calls revealed distinct DNA positioning biases, attesting to nucleotide-level accuracy. The ancient methylation levels exhibited high conservation over time, clustering closely with modern hair tissues. Using ancient methylation information, we estimated the age at death of the Saqqaq individual and illustrate how epigenetic information can be used to infer ancient gene expression. Similar epigenetic signatures were found in other fossil material, such as 110,000- to 130,000-yr-old bones, supporting the contention that ancient epigenomic information can be reconstructed from a deep past. Our findings lay the foundation for extracting epigenomic information from ancient samples, allowing shifts in epialleles to be tracked through evolutionary time, as well as providing an original window into modern epigenomics.Ancient DNA research started in the mid-1980s with the successful cloning and sequencing of a short mitochondrial DNA fragment from the quagga zebra, a species that became extinct in the early 20th century (Higuchi et al. 1984). Soon after, the invention of PCR unlocked access to this fragmented and degraded DNA material (Pääbo 1989), making it possible to amplify short gene markers of interest and compare their sequence to that from extant organisms. This illuminated a range of topics ranging from the reconstruction of the evolutionary origins of several now-extinct iconic mammals (Orlando et al. 2003; Krause et al. 2006), the evaluation of the possible role played by major past climatic changes in driving mega-fauna extinctions (Shapiro et al. 2004; Campos et al. 2010; Lorenzen et al. 2011), to the identification of the pathogens responsible for massive historical outbreaks (Taubenberger et al. 1997).However, before the advent of next-generation sequencing (NGS) platforms, the amount of ancient sequence information one had access to was limited to several tens of thousands of nucleotides at best (Noonan et al. 2005, 2006), and until very recently, sequencing whole ancient mitochondrial genomes was considered a major achievement (Cooper et al. 2001; Krause et al. 2006). Parallel sequencing of millions to billions of short DNA fragments has revolutionized ancient DNA research, and today a series of ancient genomes has been reconstructed from humans (Rasmussen et al. 2010, 2011; Keller et al. 2012; Raghavan et al. 2013), archaic hominins (Green et al. 2010; Reich et al. 2010; Meyer et al. 2012), the woolly mammoth (Miller et al. 2008), and several microbial pathogens (Bos et al. 2011; Martin et al. 2013; Schuenemann et al. 2013; Yoshida et al. 2013). Those mainly date back to recent historical periods or the Late Pleistocene, but most recently, the characterization of a 560,000- to 780,000-yr-old horse draft genome revealed that genomic information could be retrieved over much longer evolutionary time scales, probably up until the last million years (Orlando et al. 2013).Ancient genomes have provided important new insights into human evolution and dispersals (Rasmussen et al. 2010, 2011; Keller et al. 2012; Raghavan et al. 2013), revealing an admixture between contemporary human ancestors and archaic hominins (Green et al. 2010; Reich et al. 2010; Meyer et al. 2012) and multiple early human expansions into both Asia and North America (Rasmussen et al. 2010, 2011). The information gained from these samples has largely been limited to nucleotide polymorphisms. Unlike mutations, epigenetic modifications do not alter the underlying DNA sequence, but can be inherited across cell divisions and from parents to offspring and can control gene expression by reshaping cytosine methylation landscapes, nucleosome organization, and histone modification patterns. The range of biological processes that depend on some level of epigenetic regulation is diverse and includes imprinting (Bird 2002), transposition (Hollister and Gaut 2009), cell differentiation (Meissner et al. 2008), and cancer (Teschendorff et al. 2011). In this study, we use the Saqqaq genome that was retrieved from an ∼4000-yr-old tuft of hair of a Paleo-Eskimo from Greenland and sequenced to an average depth of 20× (Rasmussen et al. 2010). We demonstrate that NGS data can be used in the absence of bisulfite or further experimental treatment to directly infer genome-wide nucleosome organization and regional methylation levels, thereby providing the first survey of an ancient epigenome.