Fitting ACE Structural Equation Models to Case-Control Family Data

Investigators interested in whether a disease aggregates in families often collect case-control family data, which consist of disease status and covariate information for families selected via case or control probands. Here, we focus on the use of case-control family data to investigate the relative contributions to the disease of additive genetic effects (A), shared family environment (C), and unique environment (E). To this end, we describe a ACE model for binary family data and then introduce an approach to fitting the model to case-control family data. The structural equation model, which has been described previously, combines a general-family extension of the classic ACE twin model with a (possibly covariate-specific) liability-threshold model for binary outcomes. Our likelihood-based approach to fitting involves conditioning on the proband’s disease status, as well as setting prevalence equal to a pre-specified value that can be estimated from the data themselves if necessary. Simulation experiments suggest that our approach to fitting yields approximately unbiased estimates of the A, C, and E variance components, provided that certain commonly-made assumptions hold. These assumptions include: the usual assumptions for the classic ACE and liability-threshold models; assumptions about shared family environment for relative pairs; and assumptions about the case-control family sampling, including single ascertainment. When our approach is used to fit the ACE model to Austrian case-control family data on depression, the resulting estimate of heritability is very similar to those from previous analyses of twin data

P09-15. Selection of higher avidity HLA-restricted T cell responses as a viral adaptation strategy

Loss of immune reactivity due to HIV mutational escape is well described. Data generated from a large population-based study (n>800) suggested that certain CD8 T cell epitopes are created as a result of HIV adaptation and are associated with enhanced viral replication. Here we sought to investigate the HLA-restricted T-cell responses associated with seven such adaptations

Estimating the Prevalence of Disease Using Relatives of Case and Control Probands

We introduce a method for estimating the prevalence of disease using data from a case-control family study performed to investigate the aggregation of disease in families. The families are sampled via case and control probands, and the resulting data consist of information on disease status and covariates for the probands and their relatives. We introduce estimators for overall prevalence and for covariate stratum-specific prevalence (e.g., sex-specific prevalence) that yield approximately unbiased estimates of their population counterparts. We also introduce corresponding confidence intervals that have good coverage properties even for small prevalences. The estimators and intervals address the over-representation of diseased individuals in case-control family data by using only the relatives (of the probands) and by taking into account whether each relative was selected via a case or a control proband. Finally, we describe a simulation experiment in which the estimators and intervals were applied to case-control family datasets sampled from a fictional population that resembled the catchment area for an Austrian family study of major depressive disorder. The resulting estimates varied closely and symmetrically around their population counterparts, and the resulting intervals had good coverage properties

EFBAT: exact family-based association tests

Background: Family-based association tests are important tools for investigating genetic risk factors of complex diseases. These tests are especially valuable for being robust to population structure. We introduce a tool, EFBAT, which performs exact family-based tests of association for X-chromosome and autosomal biallelic markers. Results: The program EFBAT extends a network algorithm previously applied to autosomal markers to include the X-chromosome and to perform tests of association under the null hypotheses "no association, no linkage" and "no association in the presence of linkage" under additive, dominant and recessive genetic models. These tests are valid regardless of patterns of missing familial data. Conclusion: The general framework for performing exact family-based association tests has been usefully extended to the X-chromosome, particularly for the hypothesis of "no association in the presence of linkage" and for different genetic models

Discovery and Validation of a High-Density sub-Neptune from the K2 Mission

We report the discovery of BD+20594b, a high density sub-Neptune exoplanet, made using photometry from Campaign 4 of the two-wheeled Kepler (K2) mission, ground-based radial velocity follow-up from HARPS and high resolution lucky and adaptive optics imaging obtained using AstraLux and MagAO, respectively. The host star is a bright ($V=11.04$, $K_s = 9.37$), slightly metal poor ([Fe/H]$=-0.15\pm 0.05$ dex) solar analogue located at $152.1^{+9.7}_{-7.4}$ pc from Earth, for which we find a radius of $R_*=0.928^{+0.055}_{-0.040}R_\odot$ and a mass of $M_* = 0.961^{+0.032}_{-0.029}M_\odot$. A joint analysis of the K2 photometry and HARPS radial velocities reveal that the planet is in a $\approx 42$ day orbit around its host star, has a radius of $2.23^{+0.14}_{-0.11}R_\oplus$, and a mass of $16.3^{+6.0}_{-6.1}M_\oplus$. Although the data at hand puts the planet in the region of the mass-radius diagram where we could expect planets with a pure rock (i.e. magnesium silicate) composition using two-layer models (i.e., between rock/iron and rock/ice compositions), we discuss more realistic three-layer composition models which can explain the high density of the discovered exoplanet. The fact that the planet lies in the boundary between "possibly rocky" and "non-rocky" exoplanets, makes it an interesting planet for future RV follow-up.Comment: 12 pages, 11 figures. Accepted for publication in Ap

The Wide Brown Dwarf Binary Oph 1622-2405 and Discovery of A Wide, Low Mass Binary in Ophiuchus (Oph 1623-2402): A New Class of Young Evaporating Wide Binaries?

We imaged five objects near the star forming clouds of Ophiuchus with the Keck Laser Guide Star AO system. We resolved Allers et al. (2006)'s #11 (Oph 16222-2405) and #16 (Oph 16233-2402) into binary systems. The #11 object is resolved into a 243 AU binary, the widest known for a very low mass (VLM) binary. The binary nature of #11 was discovered first by Allers (2005) and independently here during which we obtained the first spatially resolved R~2000 near-infrared (J & K) spectra, mid-IR photometry, and orbital motion estimates. We estimate for 11A and 11B gravities (log(g)>3.75), ages (5+/-2 Myr), luminosities (log(L/Lsun)=-2.77+/-0.10 and -2.96+/-0.10), and temperatures (Teff=2375+/-175 and 2175+/-175 K). We find self-consistent DUSTY evolutionary model (Chabrier et al. 2000) masses of 17+4-5 MJup and 14+6-5 MJup, for 11A and 11B respectively. Our masses are higher than those previously reported (13-15 MJup and 7-8 MJup) by Jayawardhana & Ivanov (2006b). Hence, we find the system is unlikely a ``planetary mass binary'', (in agreement with Luhman et al. 2007) but it has the second lowest mass and lowest binding energy of any known binary. Oph #11 and Oph #16 belong to a newly recognized population of wide (>100 AU), young (<10 Myr), roughly equal mass, VLM stellar and brown dwarf binaries. We deduce that ~6+/-3% of young (<10 Myr) VLM objects are in such wide systems. However, only 0.3+/-0.1% of old field VLM objects are found in such wide systems. Thus, young, wide, VLM binary populations may be evaporating, due to stellar encounters in their natal clusters, leading to a field population depleted in wide VLM systems.Comment: Accepted version V2. Now 13 pages longer (45 total) due to a new discussion of the stability of the wide brown dwarf binary population, new summary Figure 17 now included, Astrophysical Journal 2007 in pres

Nucleosynthetic Yields from Neutron Stars Accreting in Binary Common Envelopes

© 2019 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical Society. Massive-star binaries can undergo a phase where one of the two stars expands during its advanced evolutionary stage as a giant and envelops its companion, ejecting the hydrogen envelope and tightening its orbit. Such a common envelope phase is required to tighten the binary orbit in the formation of many of the observed X-ray binaries and merging compact binary systems. In the formation scenario for neutron star binaries, the system might pass through a phase where a neutron star spirals into the envelope of its giant star companion. These phases lead to mass accretion on to the neutron star. Accretion on to these common-envelope-phase neutron stars can eject matter that has undergone burning near to the neutron star surface. This paper presents nucleosynthetic yields of this ejected matter, using population synthesis models to study the importance of these nucleosynthetic yields in a galactic chemical evolution context. Depending on the extreme conditions in temperature and density found in the accreted material, both proton-rich and neutron-rich nucleosynthesis can be obtained, with efficient production of neutron-rich isotopes of low Z material at the most extreme conditions, and proton-rich isotopes, again at low Z, in lower density models. Final yields are found to be extremely sensitive to the physical modelling of the accretion phase. We show that neutron stars accreting in binary common envelopes might be a new relevant site for galactic chemical evolution, and therefore more comprehensive studies are needed to better constrain nucleosynthesis in these objects

A CANDELS WFC3 Grism Study of Emission-Line Galaxies at z~2: A Mix of Nuclear Activity and Low-Metallicity Star Formation

We present Hubble Space Telescope Wide Field Camera 3 slitless grism spectroscopy of 28 emission-line galaxies at z~2, in the GOODS-S region of the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS). The high sensitivity of these grism observations, with 1-sigma detections of emission lines to f > 2.5x10^{-18} erg/s/cm^2, means that the galaxies in the sample are typically ~7 times less massive (median M_* = 10^{9.5} M_sun) than previously studied z~2 emission-line galaxies. Despite their lower mass, the galaxies have OIII/Hb ratios which are very similar to previously studied z~2 galaxies and much higher than the typical emission-line ratios of local galaxies. The WFC3 grism allows for unique studies of spatial gradients in emission lines, and we stack the two-dimensional spectra of the galaxies for this purpose. In the stacked data the OIII emission line is more spatially concentrated than the Hb emission line with 98.1 confidence. We additionally stack the X-ray data (all sources are individually undetected), and find that the average L(OIII)/L(0.5-10 keV) ratio is intermediate between typical z~0 obscured active galaxies and star-forming galaxies. Together the compactness of the stacked OIII spatial profile and the stacked X-ray data suggest that at least some of these low-mass, low-metallicity galaxies harbor weak active galactic nuclei.Comment: ApJ accepted. 8 pages, 6 figure