Genome-Wide Association Study Identifies a Functional SIDT2 Variant Associated With HDL-C (High-Density Lipoprotein Cholesterol) Levels and Premature Coronary Artery Disease

ObjectiveLow HDL-C (high-density lipoprotein cholesterol) is the most frequent dyslipidemia in Mexicans, but few studies have examined the underlying genetic basis. Our purpose was to identify genetic variants associated with HDL-C levels and cardiovascular risk in the Mexican population.Approach and resultsA genome-wide association studies for HDL-C levels in 2335 Mexicans, identified four loci associated with genome-wide significance: CETP, ABCA1, LIPC, and SIDT2. The SIDT2 missense Val636Ile variant was associated with HDL-C levels and was replicated in 3 independent cohorts (P=5.9×10−18 in the conjoint analysis). The SIDT2/Val636Ile variant is more frequent in Native American and derived populations than in other ethnic groups. This variant was also associated with increased ApoA1 and glycerophospholipid serum levels, decreased LDL-C (low-density lipoprotein cholesterol) and ApoB levels, and a lower risk of premature CAD. Because SIDT2 was previously identified as a protein involved in sterol transport, we tested whether the SIDT2/Ile636 protein affected this function using an in vitro site-directed mutagenesis approach. The SIDT2/Ile636 protein showed increased uptake of the cholesterol analog dehydroergosterol, suggesting this variant affects function. Finally, liver transcriptome data from humans and the Hybrid Mouse Diversity Panel are consistent with the involvement of SIDT2 in lipid and lipoprotein metabolism.ConclusionsThis is the first genome-wide association study for HDL-C levels seeking associations with coronary artery disease in the Mexican population. Our findings provide new insight into the genetic architecture of HDL-C and highlight SIDT2 as a new player in cholesterol and lipoprotein metabolism in humans

Risk Factors Associated with Adverse Fetal Outcomes in Pregnancies Affected by Coronavirus Disease 2019 (COVID-19): A Secondary Analysis of the WAPM study on COVID-19

To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Mean gestational age at diagnosis was 30.6\ub19.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible

Amplitude analysis of B0→D‾0Ds+π−B^0 \rightarrow \overline{D}^0 D_s^+ \pi^- and B+→D−Ds+π+B^+ \rightarrow D^- D_s^+ \pi^+ decays

Resonant contributions in $B^0 \rightarrow \overline{D}^0 D^+_s\pi^-$ and $B^+\rightarrow D^- D^+_s\pi^+$ decays are determined with an amplitude analysis, which is performed both separately and simultaneously, where in the latter case isospin symmetry between the decays is assumed. The analysis is based on data collected by the LHCb detector in proton-proton collisions at center-of-mass energies of 7, 8 and 13 $\rm{TeV}$. The full data sample corresponds to an integrated luminosity of 9 $\rm fb^{-1}$. A doubly charged spin-0 open-charm tetraquark candidate together with a neutral partner, both with masses near $2.9\,\rm{GeV}$, are observed in the $D_s\pi$ decay channel.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-027.html (LHCb public pages

First observation of the B+→Ds+Ds−K+B^+ \rightarrow D_s^+ D_s^- K^+ decay

The $B^+ \rightarrow D_s^+ D_s^- K^+$ decay is observed for the first time using proton-proton collision data collected by the LHCb detector at centre-of-mass energies of $7$, $8$ and $13\, \text{TeV}$, corresponding to an integrated luminosity of $9\,\text{fb}^{-1}$. Its branching fraction relative to that of the $B^{+} \rightarrow D^{+} D^{-} K^{+}$ decay is measured to be $$\frac{B\left(B^{+} \rightarrow D_s^{+} D_s^{-} K^{+}\right)}{B\left(B^{+} \rightarrow D^{+} D^{-} K^{+}\right)}=0.525 \pm 0.033 \pm 0.027 \pm 0.034,$$ where the first uncertainty is statistical, the second systematic, and the third is due to the uncertainties on the branching fractions of the $D_s^{\pm} \rightarrow K^{\mp} K^{\pm} \pi^{\pm}$ and $D^{\pm} \rightarrow K^{\mp} \pi^{\pm} \pi^{\pm}$ decays. This measurement fills an experimental gap in the knowledge of the family of Cabibbo$-$favoured $\bar{b} \rightarrow \bar{c} c \bar{s}$ transitions and opens the path for unique studies of spectroscopy in future.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-019.html (LHCb public pages

Study of the B− → Λc+Λ¯c−K− decay

The decay B − → Λ + c ¯ Λ − c K − is studied in proton-proton collisions at a center-of-mass energy of √ s = 13     TeV using data corresponding to an integrated luminosity of 5     fb − 1 collected by the LHCb experiment. In the Λ + c K − system, the Ξ c ( 2930 ) 0 state observed at the BABAR and Belle experiments is resolved into two narrower states, Ξ c ( 2923 ) 0 and Ξ c ( 2939 ) 0 , whose masses and widths are measured to be m ( Ξ c ( 2923 ) 0 ) = 2924.5 ± 0.4 ± 1.1     MeV , m ( Ξ c ( 2939 ) 0 ) = 2938.5 ± 0.9 ± 2.3     MeV , Γ ( Ξ c ( 2923 ) 0 ) = 4.8 ± 0.9 ± 1.5     MeV , Γ ( Ξ c ( 2939 ) 0 ) = 11.0 ± 1.9 ± 7.5     MeV , where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt Λ + c K − sample. Evidence of a new Ξ c ( 2880 ) 0 state is found with a local significance of 3.8 σ , whose mass and width are measured to be 2881.8 ± 3.1 ± 8.5     MeV and 12.4 ± 5.3 ± 5.8     MeV , respectively. In addition, evidence of a new decay mode Ξ c ( 2790 ) 0 → Λ + c K − is found with a significance of 3.7 σ . The relative branching fraction of B − → Λ + c ¯ Λ − c K − with respect to the B − → D + D − K − decay is measured to be 2.36 ± 0.11 ± 0.22 ± 0.25 , where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays

Direct CP violation in charmless three-body decays of B± mesons

Measurements of C P asymmetries in charmless three-body decays of B ± mesons are reported using proton-proton collision data collected by the LHCb detector, corresponding to an integrated luminosity of 5.9     fb − 1 . The previously observed C P asymmetry in B ± → π ± K + K − decays is confirmed, and C P asymmetries are observed with a significance of more than five standard deviations in the B ± → π ± π + π − and B ± → K ± K + K − decays, while the C P asymmetry of B ± → K ± π + π − decays is confirmed to be compatible with zero. The distributions of these asymmetries are also studied as a function of the three-body phase space and suggest contributions from rescattering and resonance interference processes. An indication of the presence of the decays B ± → π ± χ c 0 ( 1 P ) in both B ± → π ± π + π − and B ± → π ± K + K − decays is observed, as is C P violation involving these amplitudes