61 research outputs found
Balancing Uncertain Risks and Benefits in Human Subjects Research
October, 2005, Revised June, 2007Composed of a variety of scientific and technical experts plus a few lay members, thousands of Institutional Review Boards (IRBs) in the US must identify and assess the potential risks to human research subjects, and balance those risks against the potential benefits of the research. These assessments are laden with uncertainty, however. Most IRBs handle risk and its uncertainty by adopting a version of the precautionary principle, which is largely suggested by the Belmont Report and the Common Rule. To assess scientific merit, IRBs tacitly employ a "sanguinity principle," which treats uncertainty as inevitable in scientific progress. In balancing the uncertainties of human subjects risks and scientific benefits, IRBs use uncertainty as a bridging device that allows the approaches of science and ethics to be reconciled. Nevertheless, the flexibility and lack of consistent oversight of how IRBs apply these principles leads to frustration by investigators who are unclear about the criteria by which their proposals are evaluated
From Experts' Beliefs to Safety Standards: Explaining Preferred Radiation Protection Standards in Polarized Technical Communities
Public policy debates often involve complex, high-stakes issues in which the views of experts within scientific and technical communities play a prominent role. Disputes over appropriate governmental actions concerning global climate change, genetically modified organisms, nuclear waste disposal, cloning, and stem cell research highlight the political importance that can be attached to debates within scientific communities. Not only do these debates influence the kinds of assumed causal relationships that underlie policy alternatives (e.g., the link between CO2 concentrations in the atmosphere and global temperatures, or the dispersal patterns of pollens from genetically modified corn), but also those appointed to advisory and technical policy making positions are often chosen from the participating scientific communities. The appointment to such positions has become an increasingly contentious process; some critics contend that experts’ policy positions have trumped their scientific standing in determining appointments to important science policy boards (Revkin 2004; Mooney 2005)
Confirmation that a specific haplotype of the dopamine transporter gene is associated with Combined-Type ADHD
Objective: The primary purpose of this study was to confirm the association of a specific haplotype of the dopamine transporter gene and attention deficit hyperactivity disorder (ADHD), which could be one source of the heterogeneity seen across published studies. Method: The authors previously reported the association of ADHD with a subgroup of chromosomes containing specific alleles of two variable-number tandem repeat polymorphisms within the 3' untranslated region and intron 8 of the dopamine transporter gene. They now report on this association in a sample of ADHD combined-type probands. Results: The original observations were confirmed, with an overall odds ratio of 1.4 across samples. Conclusions: These data challenge results of meta-analyses suggesting that dopamine transporter variation does not have an effect on the risk for ADHD, and they indicate that further investigation of functional variation in the gene is required. <br/
Identifying Loci for the Overlap Between Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder Using a Genome-wide QTL Linkage Approach
GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors
Objective: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and crossvalidated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS metaanalysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. Methods: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. Results: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. Conclusions: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.</p
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
A genetic investigation of sex bias in the prevalence of attention-deficit/hyperactivity disorder
Background Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is 2-7 times more common in males than females. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases. Methods We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (20,183 cases, 35,191 controls) and Swedish populationregister data (N=77,905 cases, N=1,874,637 population controls). Results Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with rg estimates close to 1. Analyses of population data, however, indicated that females with ADHD may be at especially high risk of certain comorbid developmental conditions (i.e. autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score (PRS) analysis did not support a higher burden of ADHD common risk variants in female cases (OR=1.02 [0.98-1.06], p=0.28). In contrast, epidemiological sibling analyses revealed that the siblings of females with ADHD are at higher familial risk of ADHD than siblings of affected males (OR=1.14, [95% CI: 1.11-1.18], p=1.5E-15). Conclusions Overall, this study supports a greater familial burden of risk in females with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence
The Problem of the Withheld Compliment
Presented on February 2, 2012 from 11:00am – 12:00pm in the Office of Undergraduate Studies's Resource Room in the Clough Commons on the Georgia Tech CampusRuntime: 18:21 minutes
Between MITI and the Market: Japanese Industrial Policy for High Technology. By Daniel I. Okimoto. Stanford: Stanford University Press, 1989. 267p. $27.50.
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