GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function : a report from the COGENT consortium

CORRIGENDUM Molecular Psychiatry (2017) 22, 1651–1652 http://www.nature.com/articles/mp2017197.pdfThe complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (similar to 8M single-nucleotide polymorphisms (SNP) with minor allele frequency >= 1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome 1) associated with cognitive performance at the genome-wide significance level (PPeer reviewe

Bayesian versus frequentist statistical inference for investigating a one-off cancer cluster reported to a health department

Background. The problem of silent multiple comparisons is one of the most difficult statistical problems faced by scientists. It is a particular problem for investigating a one-off cancer cluster reported to a health department because any one of hundreds, or possibly thousands, of neighbourhoods, schools, or workplaces could have reported a cluster, which could have been for any one of several types of cancer or any one of several time periods. Methods. This paper contrasts the frequentist approach with a Bayesian approach for dealing with silent multiple comparisons in the context of a one-off cluster reported to a health department. Two published cluster investigations were re-analysed using the Dunn-Sidak method to adjust frequentist p-values and confidence intervals for silent multiple comparisons. Bayesian methods were based on the Gamma distribution. Results. Bayesian analysis with non-informative priors produced results similar to the frequentist analysis, and suggested that both clusters represented a statistical excess. In the frequentist framework, the statistical significance of both clusters was extremely sensitive to the number of silent multiple comparisons, which can only ever be a subjective "guesstimate". The Bayesian approach is also subjective: whether there is an apparent statistical excess depends on the specified prior. Conclusion. In cluster investigations, the frequentist approach is just as subjective as the Bayesian approach, but the Bayesian approach is less ambitious in that it treats the analysis as a synthesis of data and personal judgements (possibly poor ones), rather than objective reality. Bayesian analysis is (arguably) a useful tool to support complicated decision-making, because it makes the uncertainty associated with silent multiple comparisons explicit

Stable Isotope Tracking of Endangered Sea Turtles: Validation with Satellite Telemetry and δ15N Analysis of Amino Acids

Effective conservation strategies for highly migratory species must incorporate information about long-distance movements and locations of high-use foraging areas. However, the inherent challenges of directly monitoring these factors call for creative research approaches and innovative application of existing tools. Highly migratory marine species, such as marine turtles, regularly travel hundreds or thousands of kilometers between breeding and feeding areas, but identification of migratory routes and habitat use patterns remains elusive. Here we use satellite telemetry in combination with compound-specific isotope analysis of amino acids to confirm that insights from bulk tissue stable isotope analysis can reveal divergent migratory strategies and within-population segregation of foraging groups of critically endangered leatherback sea turtles (Dermochelys coriacea) across the Pacific Ocean. Among the 78 turtles studied, we found a distinct dichotomy in δ15N values of bulk skin, with distinct “low δ15N” and “high δ15N” groups. δ15N analysis of amino acids confirmed that this disparity resulted from isotopic differences at the base of the food chain and not from differences in trophic position between the two groups. Satellite tracking of 13 individuals indicated that their bulk skin δ15N value was linked to the particular foraging region of each turtle. These findings confirm that prevailing marine isoscapes of foraging areas can be reflected in the isotopic compositions of marine turtle body tissues sampled at nesting beaches. We use a Bayesian mixture model to show that between 82 and 100% of the 78 skin-sampled turtles could be assigned with confidence to either the eastern Pacific or western Pacific, with 33 to 66% of all turtles foraging in the eastern Pacific. Our forensic approach validates the use of stable isotopes to depict leatherback turtle movements over broad spatial ranges and is timely for establishing wise conservation efforts in light of this species’ imminent risk of extinction in the Pacific

Toward a “constitution” for behavioral policy-making

Behavioral policy interventions aimed at redirecting individuals’ behavior toward optimal choices are characterized by an important issue which is often overlooked: the lack of an instrument to define what “optimal” means. If agents are subject to behavioral biases leading them to make “wrong” choices, the policy-maker can no longer rely on the revealed preferences approach (e.g., what people choose is what people prefer) for defining a welfare criterion. In this article, we reiterate the argument put forward by some scholars that choosing a suitable welfare criterion once the link between observed choices and individuals’ preferences is broken becomes a problematic task. We review the state of the art in the literature and the possible approaches proposed to overcome the problem, concluding that a solution has not yet been reached. Moreover, we argue that the lack of an established welfare criterion characterizing behavioral policy-making could pave the way to government wanting to restrict individual freedom. In the absence of any legislative constraint for the executive, stating that what individuals choose is not what they prefer in principle justifies any freedom-reducing government intervention, since choices can be arbitrarily labeled “sub-optimal” or “welfare-reducing.” To avoid this risk without turning down the potential of behavioral policy-making, we propose that an independent committee establishes ex ante procedural rules and domains where behavioral policy-making can be implemented. The article suggests some possible examples of normative provisions characterizing this constitution-type document, such as the selective identification of the only sectors where behavioral policies could be effectively applied, the periodic evaluation of policy effects, and the use of sunset clauses

The association between county-level mental health provider shortage areas and suicide rates in the United States during the COVID-19 pandemic.

OBJECTIVE: Prior literature has shown that mental health provider Health Professional Shortage Areas (MHPSAs) experienced a greater increase in suicide rates compared to non-shortage areas from 2010 to 2018. Although suicide rates have been on the rise, rates have slightly decreased during the COVID-19 pandemic. This study sought to characterize the differences in suicide rate trends during the pandemic by MHPSA status. METHOD: We used generalized estimating equation regression to test the associations between MHPSA status and suicide rates from 2018 to 2021. Suicide deaths were obtained from the Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research. RESULTS: MHPSA status was associated with higher suicide rates (adjusted IRR:1.088 [95% CI, 1.024-1.156]). Furthermore, there was a significant interaction between MHPSA status and year (adjusted IRR:1.056 [95% CI, 1.022-1.091]), such that suicide rates did not significantly change among MHPSAs but slightly decreased among non-MHPSAs from 2018 to 2021. CONCLUSIONS: During the COVID-19 pandemic, there was a slight decrease in suicide rates among non-MHPSAs, while those with shortages experienced no significant changes in suicide rates. It will be important to closely monitor MHPSAs as continued at-risk regions for suicide as trendlines return to their pre-pandemic patterns

Biology and genetic diversity of phasey bean mild yellows virus, a common virus in legumes in Australia

This study examined the natural and experimental host range and aphid and graft transmission of the tentative polerovirus phasey bean mild yellows virus (PBMYV). Eleven complete coding sequences from PBMYV isolates were determined from a range of hosts and locations. We found two genetically distinct variants of PBMYV. PBMYV-1 was the originally described variant, and PBMYV-2 had a large putative recombination in open reading frame 5 such that PBMYV-1 and PBMYV-2 shared only 65-66% amino acid sequence identity in the P5 protein. The virus was transmitted by a clonal colony of cowpea aphids (Aphis craccivora) and by grafting with infected scions but was not transmitted by a clonal colony of green peach aphids (Myzus persicae). PBMYV was found in natural infections in 11 host species with a range of symptoms and severity, including seven important grain legume crops from across a wide geographic area in Australia. PBMYV was common and widespread in the tropical weed phasey bean (Macroptilium lathyroides), but it is likely that there are other major alternative hosts for the virus in temperate regions of Australia. The experimental host range of PBMYV included the Fabaceae hosts chickpea (Cicer arietinum), faba bean (Vicia faba), pea (Pisum sativum), and phasey bean, but transmissions failed to infect several other members of the families Asteraceae, Cucurbitaceae, Fabaceae and Solanaceae. PBMYV was commonly found in grain legume crops in eastern and western Australia, sometimes at greater than 90% incidence. This new knowledge about PBMYV warrants further assessments of its economic impact on important grain legume crops