Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Solute and particle retention in a small grazing antelope, the blackbuck (Antilope cervicapra)

Digesta retention patterns have been suggested to play a major role in ruminant diversification. Two major digestion types have been proposed, termed ‘cattle-type’ and ‘moose-type’, that broadly correspond to the feeding categories of grazers and intermediate feeders on the one, and browsers on the other hand.Wemeasured and calculated the mean retention time (MRT) of a solute and a particle (<2mm) marker in the gastrointestinal tract (GIT) and the reticulorumen (RR) of a small grazer, the Indian blackbuck (Antilope cervicapra, n = 5, body mass of 26 ± 4 kg) and an intermediate feeder, the nilgai (Boselaphus tragocamelus, n = 5, body mass of 168 ± 21 kg). MRTsolute and MRTparticle were 29 ± 4.1 h and 60 ± 6.6 h in blackbuck and 28 ± 2.5 h and 54±8.9 h in the nilgai for the GIT, and 14±1.7 h, 45±5.0 h, 19±2.0 h and 45±8.4 h for the RR, respectively. With a selectivity factor (SF, the ratio of MRTparticle to MRTsolute) in the RR of 3.2 ± 0.28 for blackbuck and 2.3 ± 0.36 for nilgai, both species are clearly in the category of ‘cattle-type’ ruminants. In particular, the high SFRR of blackbuck, in spite of its small body size, is remarkable, and leads to specific predictions on the RR anatomy of this species (such as a particularly large omasum), which can be tested in further studies. The adaptive value of a high SFRR is mainly considered as an increase in microbial productivity in the RR

Solute and particle retention in a small grazing antelope, the blackbuck (Antilope cervicapra)

Digesta retention patterns have been suggested to play a major role in ruminant diversification. Two major digestion types have been proposed, termed 'cattle-type' and 'moose-type', that broadly correspond to the feeding categories of grazers and intermediate feeders on the one, and browsers on the other hand. We measured and calculated the mean retention time (MRT) of a solute and a particle (>2mm) marker in the gastrointestinal tract (GIT) and the reticulorumen (RR) of a small grazer, the Indian blackbuck (Antilope cervicapra, n=5, body mass of 26±4kg) and an intermediate feeder, the nilgai (Boselaphus tragocamelus, n=5, body mass of 168±21kg). MRTsolute and MRTparticle were 29±4.1h and 60±6.6h in blackbuck and 28±2.5h and 54±8.9h in the nilgai for the GIT, and 14±1.7h, 45±5.0h, 19±2.0h and 45±8.4h for the RR, respectively. With a selectivity factor (SF, the ratio of MRTparticle to MRTsolute) in the RR of 3.2±0.28 for blackbuck and 2.3±0.36 for nilgai, both species are clearly in the category of 'cattle-type' ruminants. In particular, the high SFRR of blackbuck, in spite of its small body size, is remarkable, and leads to specific predictions on the RR anatomy of this species (such as a particularly large omasum), which can be tested in further studies. The adaptive value of a high SFRR is mainly considered as an increase in microbial productivity in the RR; exemplary estimations based on the measured passage rates of solutes indicate an 8% higher production of microbial mass in blackbuck compared to nilgai

Retention of solute and particle markers in the digestive tract of captive Somali wild asses (Equus africanus somaliensis)

In contrast to the domestic horse, whose digestive physiology has been thoroughly investigated, knowledge on the digestive physiology of wild equids is scarce. Comparisons between the domestic horse and the domestic donkey suggest that wild asses might achieve higher digestibilities. This could derive from longer retention times or a greater difference in the mean retention time (MRT) of particles vs. fluid (the selectivity factor (SF)). Here, we measured MRT of a solute (fluid; MRTsolute) and a particle (<2 mm; MRTparticle) marker in five captive male Somali wild asses (Equus africanus somaliensis) fed a diet of 95% grass hay. At a mean dry matter intake of 94 ± 3 g kg−0.75 day−1, MRTsolute was 33.3 ± 5.4 h and MRTparticle 39.6 ± 3.9 h, resulting in a SF of 1.21 ± 0.14. For their food intake, Somali wild asses appeared to have slightly higher MRTparticle than expected based on domestic equid data, in contrast to Grevy zebras (Equus grevyi), potentially indicating higher capacities of the digestive tract. However, considering data on domestic horses, donkeys, and zebra, there was no evident difference in the SF of wild equids compared to domestic ones. Together with an absence of reported anatomical differences in the digestive tract of wild and domestic equids, the data suggest a general similarity in the digestive physiology of equid species that contrasts with the diversity in the digestive physiology of ruminants, and that might be one contributing factor to a lack of sympatric, niche-differentiated equid species

Plastic ingestion and trace element contamination of Manx shearwaters Puffinus puffinus on the Faroe Islands

Procellariiform seabirds can accumulate high levels of plastic in their gastrointestinal tracts, which can cause physical damage and potentially provides a contamination route for trace elements. We examined plastic ingestion and trace element contamination of fledgling Manx shearwaters Puffinus puffinus that were harvested for human consumption in 2003 and 2018 on Skúvoy, Faroe Islands (North Atlantic Ocean). Overall, 88% of fledglings contained plastic in their gastrointestinal tracts, with a mean (± SD) of 7.2 ± 6.6 items weighing 0.007 ± 0.016 g. Though the incidence was similar, fledglings ingested significantly more plastic in 2018 compared to 2003. Hepatic trace element concentrations were unrelated to plastic ingestion. Hepatic carbon (δ13C) and nitrogen (δ15N) stable isotope values were significantly lower in birds sampled in 2018 versus 2003, potentially reflecting further offshore feeding at lower trophic levels. Future research is needed to understand the extent of plastic ingestion by Faroe Islands seabirds

Solute and particle retention in the digestive tract of the Phillip's dikdik (Madoqua saltiana phillipsi), a very small browsing ruminant: Biological and methodological implications

Morphological characteristics of the forestomach, as well as reports of a natural diet that mostly excludes monocots, suggest that dikdiks (Madoqua spp.), among smallest extant ruminants, should have a ‘moosetype’ forestomach physiology characterised by a low degree of selective particle retention. We tested this assumption in a series of feeding experiments with 12 adult Phillip's dikdiks (Madoqua saltiana phillipsi) on three different intake levels per animal, using cobalt-EDTA as a solute marker and a ‘conventional’ chromiummordanted fibre (b2 mm; mean particle size 0.63 mm) marker for the particle phase. Body mass had no influence on retention measurements, whereas food intake level clearly had. Drinking water intake was not related to the retention of the solute marker. In contrast to our expectations, the particle marker was retained distinctively longer than the solute marker. Comparisons with results in larger ruminants and with faecal particle sizes measured in dikdiks suggested that in these small animals, the chosen particle marker was above the critical size threshold, above which particle delay in the forestomach is not only due to selective particle retention (as compared to fluids), but additionally due to the ruminal particle sorting mechanism that retains particles above this threshold longer than particles below this threshold. A second study with a similar marker of a lower mean particle size (0.17 mm, which is below the faecal particle size reported for dikdiks) resulted in particle and fluid retention patterns similar to those documented in other ‘moose-type’ ruminants. Nevertheless, even this smaller particle marker yielded retention times that were longer than those predicted by allometric equations based on quarter-power scaling, providing further support for observations that small ruminants generally achieve longer retention times and higher digestive efficiencies than expected based on their body size

Pattern and timing of diversification of Cetartiodactyla (Mammalia, Laurasiatheria), as revealed by a comprehensive analysis of mitochondrial genomes

The order Cetartiodactyla includes cetaceans (whales, dolphins and porpoises) that are found in all oceans and seas, as well as in some rivers, and artiodactyls (ruminants, pigs, peccaries, hippos, camels and llamas) that are present on all continents, except Antarctica and until recent invasions, Australia. There are currently 332 recognized cetartiodactyl species, which are classified into 132 genera and 22 families. Most phylogenetic studies have focused on deep relationships, and no comprehensive time-calibrated tree for the group has been published yet. In this study, 128 new complete mitochondrial genomes of Cetartiodactyla were sequenced and aligned with those extracted from nucleotide databases. Our alignment includes 14,902 unambiguously aligned nucleotide characters for 210 taxa, representing 183 species, 107 genera, and all cetartiodactyl families. Our mtDNA data produced a statistically robust tree, which is largely consistent with previous classifications. However, a few taxa were found to be para- or polyphyletic, including the family Balaenopteridae, as well as several genera and species. Accordingly, we propose several taxonomic changes in order to render the classification compatible with our molecular phylogeny. In some cases, the results can be interpreted as possible taxonomic misidentification or evidence for mtDNA introgression. The existence of three new cryptic species of Ruminantia should therefore be confirmed by further analyses using nuclear data. We estimate divergence times using Bayesian relaxed molecular clock models. The deepest nodes appeared very sensitive to prior assumptions leading to unreliable estimates, primarily because of the misleading effects of rate heterogeneity, saturation and divergent outgroups. In addition, we detected that Whippomorpha contains slow-evolving taxa, such as large whales and hippos, as well as fast-evolving taxa, such as river dolphins. Our results nevertheless indicate that the evolutionary history of cetartiodactyls was punctuated by four main phases of rapid radiation during the Cenozoic era: the sudden occurrence of the three extant lineages within Cetartiodactyla (Cetruminantia, Suina and Tylopoda); the basal diversification of Cetacea during the Early Oligocene; and two radiations that involve Cetacea and Pecora, one at the Oligocene/Miocene boundary and the other in the Middle Miocene. In addition, we show that the high species diversity now observed in the families Bovidae and Cervidae accumulated mainly during the Late Miocene and Plio-Pleistocene. © 2011 Académie des sciences