A lesson not learned: allele misassignment

Misassigned alleles can annihilate efforts to control quality in otherwise well-designed genetic association analyses. To date, the issue remains underreported, as is exemplified by studies of a diallelic DRD2 missense variant in schizophrenia. For this variant, allele frequency data have been either misassigned, or incorrectly cited on four consecutive occasions. Contrary to conjecture, low heterozygosity has not guarded against the error with regard to rs1801028, a SNP that features a canonical base pair transversion, G:C. Measures are discussed that may help to identify misassigned alleles, and to avoid related perils pending more systematic investigation of this confounder in genotype-phenotype associations

Clouded issues for PHACTR1

I have read with interest the recent paper by Han and coworkers [1] on the putative effects of a PHACTR1 variant in the context of coronary artery disease. The authors conclude to a significant risk-enhancing role of rs12526453 on the grounds of 19 earlier case-control studies. [...

Deep resequencing of the voltage-gated potassium channel subunit KCNE3 gene in chronic tinnitus

Membrane-stabilizing drugs have long been used for the treatment of chronic tinnitus, suggesting an underlying disturbance of sensory excitability due to changes in ion conductance. The present study addresses the potassium channel subunit gene KCNE3 as a potential candidate for tinnitus susceptibility. 288 Caucasian outpatients with a diagnosis of chronic tinnitus were systematically screened for mutations in the KCNE3 open reading frame and in the adjacent region by direct sequencing. Allele frequencies were determined for 11 known variants of which two (F66F and R83H) were polymorphic but were not associated with the disorder. No novel variants were identified and only three carriers of R83H were noted. However, owing to a lack of power, our study can neither rule out effects of KCNE3 on the risk for developing chronic tinnitus, nor can it exclude a role in predicting the severity of tinnitus. More extensive investigations are invited, including tests for possible effects of variation in this ion channel protein on the response to treatment

PON1 L55M in ischemic stroke

I have read with interest a recent report by Shao and coworkers on the putative role of PON1 in ischemic stroke [1]. In their report, the authors refute an association of a missense substitution on the phenotype under study based on earlier research. It appears unlikely, however, that the results can be upheld in the present form

Weighting (Version 2.0)

This contribution deals with the fundamental principles of weighting; the various types of weighting are taken into account. Terms such as design weighting and adjustment weighting are explained, and the Horvitz-Thompson estimator and the GREG estimator are presented

Risk Attitudes and Birth Order

Risk attitudes play important roles in health behavior and everyday decision making. It is unclear, however, whether these attitudes can be predicted from birth order. We investigated 200 mostly male volunteers from two distinct settings. After correcting for multiple comparisons, for the number of siblings and for confounding by gender, ordinal position predicted perception of health-related risks among participants in extreme sports (p < .01). However, the direction of the effect contradicted Adlerian theory. Except for alcohol consumption, these findings extended to self-reported risk behavior. Together, the data call for a cautious stand on the impact of birth order on risk attitudes

Gewichtung (Version 1.1)

In diesem Kapitel werden die Grundlagen der Gewichtung behandelt. Dabei werden die verschiedenen Arten der Gewichtung berücksichtigt. Termini wie Designgewichtung und Anpassungsgewichtung werden erläutert. Neben dem Horvitz-Thompson Schätzer wird auch der GREG-Schätzer vorgestellt

From 3D hydrodynamic simulations of common-envelope interaction to gravitational-wave mergers

Modeling the evolution of progenitors of gravitational-wave merger events in binary stars faces two major uncertainties: the common-envelope phase and supernova kicks. These two processes are critical for the final orbital configuration of double compact-object systems with neutron stars and black holes. Predictive one-dimensional models of common-envelope interaction are lacking and multidimensional simulations are challenged by the vast range of relevant spatial and temporal scales. Here, we present three-dimensional hydrodynamic simulations of the common-envelope interaction of an initially $10\,M_{\odot}$ red supergiant primary star with a black-hole and a neutron-star companion. We show that the high-mass regime is accessible to full ab-initio simulations. Nearly complete envelope ejection is reached assuming that all recombination energy still available at the end of our simulation continues to help unbinding the envelope. In contrast to previous assumptions, we find that the dynamical plunge-in of both companions terminates at orbital separations too wide for gravitational waves to merge the systems in a Hubble time. We discuss the further evolution of the system based on analytical estimates. A subsequent mass-transfer episode from the remaining $3\,M_{\odot}$ core of the supergiant to the compact companion does not shrink the orbit sufficiently either. A neutron-star--neutron-star and neutron-star--black-hole merger is still expected for a fraction of the systems if the supernova kick aligns favorably with the orbital motion. For double neutron star (neutron-star--black-hole) systems we estimate mergers in about $9 \%$ ($1 \%$) of cases while about $77 \%$ ($94 \%$) of binaries are disrupted, i.e., supernova kicks actually enable gravitational-wave mergers in our cases; however, we expect a reduction in predicted gravitational-wave merger events. (abbr.)Comment: 16 pages, 11 figures, accepted by A&

Resequencing of the auxiliary GABAB receptor subunit gene KCTD12 in chronic tinnitus

Tinnitus is a common and often incapacitating hearing disorder marked by the perception of phantom sounds. Susceptibility factors remain largely unknown but GABAB receptor signaling has long been implicated in the response to treatment and, putatively, in the etiology of the disorder. We hypothesized that variation in KCTD12, the gene encoding an auxiliary subunit of GABAB receptors, could help to predict the risk of developing tinnitus. Ninety-five Caucasian outpatients with a diagnosis of chronic tinnitus were systematically screened for mutations in the KCTD12 open reading frame and the adjacent 3′ untranslated region by Sanger sequencing. Allele frequencies were determined for 14 known variants of which three (rs73237446, rs34544607, and rs41287030) were polymorphic. When allele frequencies were compared to data from a large reference population of European ancestry, rs34544607 was associated with tinnitus (p = 0.04). However, KCTD12 genotype did not predict tinnitus severity (p = 0.52) and the association with rs34544607 was weakened after screening 50 additional cases (p = 0.07). Pending replication in a larger cohort, KCTD12 may act as a risk modifier in chronic tinnitus. Issues that are yet to be addressed include the effects of neighboring variants, e.g., in the KCTD12 gene regulatory region, plus interactions with variants of GABAB1 and GABAB2