Assessing individual differences in genome-wide gene expression in human whole blood: reliability over four hours and stability over 10 months.

Studying the causes and correlates of natural variation in gene expression in healthy populations assumes that individual differences in gene expression can be reliably and stably assessed across time. However, this is yet to be established. We examined 4-hour test-retest reliability and 10 month test-retest stability of individual differences in gene expression in ten 12-year-old children. Blood was collected on four occasions: 10 a.m. and 2 p.m. on Day 1 and 10 months later at 10 a.m. and 2 p.m. Total RNA was hybridized to Affymetrix-U133 plus 2.0 arrays. For each probeset, the correlation across individuals between 10 a.m. and 2 p.m. on Day 1 estimates test-retest reliability. We identified 3,414 variable and abundantly expressed probesets whose 4-hour test-retest reliability exceeded .70, a conventionally accepted level of reliability, which we had 80% power to detect. Of the 3,414 reliable probesets, 1,752 were also significantly reliable 10 months later. We assessed the long-term stability of individual differences in gene expression by correlating the average expression level for each probe-set across the two 4-hour assessments on Day 1 with the average level of each probe-set across the two 4-hour assessments 10 months later. 1,291 (73.7%) of the 1,752 probe-sets that reliably detected individual differences across 4 hours on two occasions, 10 months apart, also stably detected individual differences across 10 months. Heritability, as estimated from the MZ twin intraclass correlations, is twice as high for the 1,752 reliable probesets versus all present probesets on the array (0.68 vs 0.34), and is even higher (0.76) for the 1,291 reliable probesets that are also stable across 10 months. The 1,291 probesets that reliably detect individual differences from a single peripheral blood collection and stably detect individual differences over 10 months are promising targets for research on the causes (e.g., eQTLs) and correlates (e.g., psychopathology) of individual differences in gene expression

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

All-sky search for long-duration gravitational wave transients with initial LIGO

We present the results of a search for long-duration gravitational wave transients in two sets of data collected by the LIGO Hanford and LIGO Livingston detectors between November 5, 2005 and September 30, 2007, and July 7, 2009 and October 20, 2010, with a total observational time of 283.0 days and 132.9 days, respectively. The search targets gravitational wave transients of duration 10-500 s in a frequency band of 40-1000 Hz, with minimal assumptions about the signal waveform, polarization, source direction, or time of occurrence. All candidate triggers were consistent with the expected background; as a result we set 90% confidence upper limits on the rate of long-duration gravitational wave transients for different types of gravitational wave signals. For signals from black hole accretion disk instabilities, we set upper limits on the source rate density between 3.4×10-5 and 9.4×10-4 Mpc-3 yr-1 at 90% confidence. These are the first results from an all-sky search for unmodeled long-duration transient gravitational waves. © 2016 American Physical Society

All-sky search for long-duration gravitational wave transients with initial LIGO

We present the results of a search for long-duration gravitational wave transients in two sets of data collected by the LIGO Hanford and LIGO Livingston detectors between November 5, 2005 and September 30, 2007, and July 7, 2009 and October 20, 2010, with a total observational time of 283.0 days and 132.9 days, respectively. The search targets gravitational wave transients of duration 10-500 s in a frequency band of 40-1000 Hz, with minimal assumptions about the signal waveform, polarization, source direction, or time of occurrence. All candidate triggers were consistent with the expected background; as a result we set 90% confidence upper limits on the rate of long-duration gravitational wave transients for different types of gravitational wave signals. For signals from black hole accretion disk instabilities, we set upper limits on the source rate density between 3.4×10-5 and 9.4×10-4 Mpc-3 yr-1 at 90% confidence. These are the first results from an all-sky search for unmodeled long-duration transient gravitational waves. © 2016 American Physical Society

Open data from the third observing run of LIGO, Virgo, KAGRA, and GEO

The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in 2019 April and lasting six months, O3b starting in 2019 November and lasting five months, and O3GK starting in 2020 April and lasting two weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main data set, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages

Language-impaired children: no sign of the FOXP2 mutation

A mutation in the FOXP2 gene has been found to be responsible for the autosomal dominant inheritance of a severe form of speech and language impairment in a family known as KE. We genotyped the FOXP2 mutation for 270 4-year-old children selected for low general language scores from a representative community sample of more than 18,000 children. No language-impaired child had the FOXP2 mutation. Although rare severe disorders such as those of the KE family are often caused by a single gene, common disorders such as language impairment are more likely to be the quantitative extreme of the same multiple genetic factors responsible for heritability throughout the distribution