The semimajor axis and planet insolation flux of Kepler-538b were incorrectly calculated in the published article. This error did not impact any other parameters or any other results in the paper. Table 2 has been included in full here with the corrected semimajor axis and planet insolation flux values. We thank Arbab I. Arbab and Charles D. Fortenbach for bringing this to our attention.(Table Presented).

K2-291 is a solar-type star with a radius of R ∗ = 0.899 ±0.034 R and mass of M ∗ = 0.934 ±0.038 M . From the K2 C13 data, we found one super-Earth planet (R p = 1.589 -0.072+0.095 R ⊕ ) transiting this star on a short period orbit (P = 2.225177 -6.8e-5+6.6e-5 days). We followed this system up with adaptive-optic imaging and spectroscopy to derive stellar parameters, search for stellar companions, and determine a planet mass. From our 75 radial velocity measurements using High Resolution Echelle Spectrometer on Keck I and High Accuracy Radial velocity Planet Searcher in the northern hemisphere on Telescopio Nazionale Galileo, we constrained the mass of K2-291 b to M p = 6.49 ±1.16 M ⊕ . We found it necessary to model correlated stellar activity radial velocity signals with a Gaussian process (GP) in order to more accurately model the effect of stellar noise on our data; the addition of the GP also improved the precision of this mass measurement. With a bulk density of ρ = 8.84 -2.03+2.50 g cm -3 , the planet is consistent with an Earth-like rock/iron composition and no substantial gaseous envelope. Such an envelope, if it existed in the past, was likely eroded away by photoevaporation during the first billion years of the star's lifetime.

Rationale

Obstructive sleep apnea is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. Although there is strong clinical and epidemiologic evidence supporting the importance of genetic factors in influencing obstructive sleep apnea, its genetic basis is still largely unknown. Prior genetic studies focused on traits defined using the apnea-hypopnea index, which contains limited information on potentially important genetically determined physiologic factors, such as propensity for hypoxemia and respiratory arousability.

Objectives

To define novel obstructive sleep apnea genetic risk loci for obstructive sleep apnea, we conducted genome-wide association studies of quantitative traits in Hispanic/Latino Americans from three cohorts.

Methods

Genome-wide data from as many as 12,558 participants in the Hispanic Community Health Study/Study of Latinos, Multi-Ethnic Study of Atherosclerosis, and Starr County Health Studies population-based cohorts were metaanalyzed for association with the apnea-hypopnea index, average oxygen saturation during sleep, and average respiratory event duration.

Measurements and main results

Two novel loci were identified at genome-level significance (rs11691765, GPR83, P = 1.90 × 10^-8 for the apnea-hypopnea index, and rs35424364; C6ORF183/CCDC162P, P = 4.88 × 10^-8 for respiratory event duration) and seven additional loci were identified with suggestive significance (P < 5 × 10^-7). Secondary sex-stratified analyses also identified one significant and several suggestive associations. Multiple loci overlapped genes with biologic plausibility.

Conclusions

These are the first genome-level significant findings reported for obstructive sleep apnea-related physiologic traits in any population. These findings identify novel associations in inflammatory, hypoxia signaling, and sleep pathways.

Obstructive sleep apnea (OSA) is a common disorder associated with increased risk of cardiovascular disease and mortality. Its prevalence and severity vary across ancestral background. Although OSA traits are heritable, few genetic associations have been identified. To identify genetic regions associated with OSA and improve statistical power, we applied admixture mapping on three primary OSA traits [the apnea hypopnea index (AHI), overnight average oxyhemoglobin saturation (SaO2) and percentage time SaO2 < 90%] and a secondary trait (respiratory event duration) in a Hispanic/Latino American population study of 11 575 individuals with significant variation in ancestral background. Linear mixed models were performed using previously inferred African, European and Amerindian local genetic ancestry markers. Global African ancestry was associated with a lower AHI, higher SaO2 and shorter event duration. Admixture mapping analysis of the primary OSA traits identified local African ancestry at the chromosomal region 2q37 as genome-wide significantly associated with AHI (P < 5.7 × 10-5), and European and Amerindian ancestries at 18q21 suggestively associated with both AHI and percentage time SaO2 < 90% (P < 10-3). Follow-up joint ancestry-SNP association analyses identified novel variants in ferrochelatase (FECH), significantly associated with AHI and percentage time SaO2 < 90% after adjusting for multiple tests (P < 8 × 10-6). These signals contributed to the admixture mapping associations and were replicated in independent cohorts. In this first admixture mapping study of OSA, novel associations with variants in the iron/heme metabolism pathway suggest a role for iron in influencing respiratory traits underlying OSA.

Background

Rare genetic variants influence blood pressure (BP).

Methods and results

Whole-exome sequencing was performed on DNA samples from 17 956 individuals of European ancestry and African ancestry (14 497, first-stage discovery and 3459, second-stage discovery) to examine the effect of rare variants on hypertension and 4 BP traits: systolic BP, diastolic BP, pulse pressure, and mean arterial pressure. Tests of ≈170 000 common variants (minor allele frequency, ≥1%; statistical significance, P≤2.9×10(-7)) and gene-based tests of rare variants (minor allele frequency, <1%; ≈17 000 genes; statistical significance, P≤1.5×10(-6)) were evaluated for each trait and ancestry, followed by multiethnic meta-analyses. In the first-stage discovery, rare coding variants (splicing, stop-gain, stop-loss, nonsynonymous variants, or indels) in CLCN6 were associated with lower diastolic BP (cumulative minor allele frequency, 1.3%; β=-3.20; P=4.1×10(-6)) and were independent of a nearby common variant (rs17367504) previously associated with BP. CLCN6 rare variants were also associated with lower systolic BP (β=-4.11; P=2.8×10(-4)), mean arterial pressure (β=-3.50; P=8.9×10(-6)), and reduced hypertension risk (odds ratio, 0.72; P=0.017). Meta-analysis of the 2-stage discovery samples showed that CLCN6 was associated with lower diastolic BP at exome-wide significance (cumulative minor allele frequency, 1.1%; β=-3.30; P=5.0×10(-7)).

Conclusions

These findings implicate the effect of rare coding variants in CLCN6 in BP variation and offer new insights into BP regulation.

Platelets play an essential role in hemostasis and thrombosis. We performed a genome-wide association study of platelet count in 12,491 participants of the Hispanic Community Health Study/Study of Latinos by using a mixed-model method that accounts for admixture and family relationships. We discovered and replicated associations with five genes (ACTN1, ETV7, GABBR1-MOG, MEF2C, and ZBTB9-BAK1). Our strongest association was with Amerindian-specific variant rs117672662 (p value = 1.16 × 10(-28)) in ACTN1, a gene implicated in congenital macrothrombocytopenia. rs117672662 exhibited allelic differences in transcriptional activity and protein binding in hematopoietic cells. Our results underscore the value of diverse populations to extend insights into the allelic architecture of complex traits.

US Hispanic/Latino individuals are diverse in genetic ancestry, culture, and environmental exposures. Here, we characterized and controlled for this diversity in genome-wide association studies (GWASs) for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We simultaneously estimated population-structure principal components (PCs) robust to familial relatedness and pairwise kinship coefficients (KCs) robust to population structure, admixture, and Hardy-Weinberg departures. The PCs revealed substantial genetic differentiation within and among six self-identified background groups (Cuban, Dominican, Puerto Rican, Mexican, and Central and South American). To control for variation among groups, we developed a multi-dimensional clustering method to define a "genetic-analysis group" variable that retains many properties of self-identified background while achieving substantially greater genetic homogeneity within groups and including participants with non-specific self-identification. In GWASs of 22 biomedical traits, we used a linear mixed model (LMM) including pairwise empirical KCs to account for familial relatedness, PCs for ancestry, and genetic-analysis groups for additional group-associated effects. Including the genetic-analysis group as a covariate accounted for significant trait variation in 8 of 22 traits, even after we fit 20 PCs. Additionally, genetic-analysis groups had significant heterogeneity of residual variance for 20 of 22 traits, and modeling this heteroscedasticity within the LMM reduced genomic inflation for 19 traits. Furthermore, fitting an LMM that utilized a genetic-analysis group rather than a self-identified background group achieved higher power to detect previously reported associations. We expect that the methods applied here will be useful in other studies with multiple ethnic groups, admixture, and relatedness.

Kepler-454 (KOI-273) is a relatively bright (V = 11.69 mag), Sun-like star that hosts a transiting planet candidate in a 10.6 day orbit. From spectroscopy, we estimate the stellar temperature to be 5687 ± 50 K, its metallicity to be [m/H] = 0.32 ± 0.08, and the projected rotational velocity to be v sin i < 2.4 km s-1. We combine these values with a study of the asteroseismic frequencies from short cadence Kepler data to estimate the stellar mass to be , the radius to be 1.066 ± 0.012 Ro, and the age to be Gyr. We estimate the radius of the 10.6 day planet as 2.37 ± 0.13 R⊕. Using 63 radial velocity observations obtained with the HARPS-N spectrograph on the Telescopio Nazionale Galileo and 36 observations made with the HIRES spectrograph at the Keck Observatory, we measure the mass of this planet to be 6.8 ± 1.4 M⊕. We also detect two additional non-transiting companions, a planet with a minimum mass of 4.46 ± 0.12 MJ in a nearly circular 524 day orbit and a massive companion with a period >10 years and mass >12.1 MJ. The 12 exoplanets with radii <2.7 R⊕ and precise mass measurements appear to fall into two populations, with those <1.6 R⊕ following an Earth-like composition curve and larger planets requiring a significant fraction of volatiles. With a density of 2.76 ± 0.73 g cm-3, Kepler-454b lies near the mass transition between these two populations and requires the presence of volatiles and/or H/He gas.

HD 3167 is a bright (V = 8.9), nearby K0 star observed by the NASA K2 mission (EPIC 220383386), hosting two small, short-period transiting planets. Here we present the results of a multi-site, multi-instrument radial-velocity campaign to characterize the HD 3167 system. The masses of the transiting planets are 5.02 ±0.38 M+for HD 3167 b, a hot super-Earth with a likely rocky composition (ρb = 5.60 +2.15-1.43= g cm-3), and 9.80 +1.30-1.24 M+for HD 3167 c, a warm sub-Neptune with a likely substantial volatile complement (pc = 1.97 0.94-0.59 g cm-3). We explore the possibility of atmospheric composition analysis and determine that planet c is amenable to transmission spectroscopy measurements, and planet b is a potential thermal emission target. We detect a third, non-transiting planet, HD 3167 d, with a period of 8.509 ±0.045 d (between planets b and c) and a minimum mass of 6.90 ±0.71 M⊕. We are able to constrain the mutual inclination of planet d with planets b and c: we rule out mutual inclinations below 1.°3 because we do not observe transits of planet d. From 1.°3 to 40°, there are viewing geometries invoking special nodal configurations, which result in planet d not transiting some fraction of the time. From 40° to 60°, Kozai-Lidov oscillations increase the system's instability, but it can remain stable for up to 100 Myr. Above 60°, the system is unstable. HD 3167 promises to be a fruitful system for further study and a preview of the many exciting systems expected from the upcoming NASA TESS mission.

Rheumatoid arthritis (RA) and osteoporosis (OP) are two comorbid complex inflammatory conditions with evidence of shared genetic background and causal relationships. We aimed to clarify the genetic architecture underlying RA and various OP phenotypes while additionally considering an inflammatory component, C-reactive protein (CRP). Genome-wide association study summary statistics were acquired from the GEnetic Factors for OSteoporosis Consortium, Cohorts for Heart and Aging Research Consortium and UK Biobank. Mendelian randomization (MR) was used to detect the presence of causal relationships. Colocalization analysis was performed to determine shared genetic variants between CRP and OP phenotypes. Analysis of pleiotropy between traits owing to shared causal single nucleotide polymorphisms (SNPs) was performed using PL eiotropic A nalysis under CO mposite null hypothesis (PLACO). MR analysis was suggestive of horizontal pleiotropy between RA and OP traits. RA was a significant causal risk factor for CRP (β = 0.027, 95% confidence interval = 0.016-0.038). There was no evidence of CRP→OP causal relationship, but horizontal pleiotropy was apparent. Colocalization established shared genomic regions between CRP and OP, including GCKR and SERPINA1 genes. Pleiotropy arising from shared causal SNPs revealed through the colocalization analysis was all confirmed by PLACO. These genes were found to be involved in the same molecular function 'protein binding' (GO:0005515) associated with RA, OP and CRP. We identified three major components explaining the epidemiological relationship among RA, OP and inflammation: (1) Pleiotropy explains a portion of the shared genetic relationship between RA and OP, albeit polygenically; (2) RA contributes to CRP elevation and (3) CRP, which is influenced by RA, demonstrated pleiotropy with OP.