Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

Differential effects of antiepileptic drugs on neonatal outcomes

Offspring of women with epilepsy (WWE) on AEDs are at increased risks for major congenital malformations and reduced cognition. They may be at risk for other adverse neonatal outcomes. Women with epilepsy on carbamazepine (CBZ), lamotrigine (LTG), phenytoin (PHT), or valproate (VPA) monotherapy were enrolled in a prospective, observational, multicenter study of the neurodevelopmental effects of AEDs. The odds ratio for small for gestational age (SGA) was higher for VPA vs. PHT, VPA vs. LTG, and CBZ vs. PHT. Microcephaly rates were elevated to 12% for all newborns and at 12months old, but normalized by age 24months. Reduced Apgar scores occurred more frequently in the VPA and PHT groups at 1min, but scores were near normal in all groups at 5min. This study demonstrates increased risks for being born SGA in the VPA and CBZ groups, and transiently reduced Apgar scores in the VPA and PHT groups. Differential risks among the AEDs can help inform decisions about AED selection for women during childbearing years. ► Neonates exposed to VPA or CBZ in utero are at higher risk of being born SGA. ► Apgar scores were lower at 1min in the VPA and PHT newborns. ► Differential risks can help decisions about AED selection in women with epilepsy

Functional distinctiveness of major plant lineages

Plant traits vary widely across species and underpin differences in ecological strategy. Despite centuries of interest, the contributions of different evolutionary lineages to modern-day functional diversity remain poorly quantified. Expanding data bases of plant traits plus rapidly improving phylogenies enable for the first time a data-driven global picture of plant functional diversity across the major clades of higher plants. We mapped five key traits relevant to metabolism, resource competition and reproductive strategy onto a phylogeny across 48324 vascular plant species world-wide, along with climate and biogeographic data. Using a novel metric, we test whether major plant lineages are functionally distinctive. We then highlight the trait-lineage combinations that are most functionally distinctive within the present-day spread of ecological strategies. For some trait-clade combinations, knowing the clade of a species conveys little information to neo- and palaeo-ecologists. In other trait-clade combinations, the clade identity can be highly revealing, especially informative clade-trait combinations include Proteaceae, which is highly distinctive, representing the global slow extreme of the leaf economic spectrum. Magnoliidae and Rosidae contribute large leaf sizes and seed masses and have distinctively warm, wet climatic distributions. Synthesis. This analysis provides a shortlist of the most distinctive trait-lineage combinations along with their geographic and climatic context: a global view of extant functional diversity across the tips of the vascular plant phylogeny. This analysis provides a shortlist of the most distinctive trait-lineage combinations along with their geographic and climatic context: a global view of extant functional diversity across the tips of the vascular plant phylogeny. © 2014 British Ecological Society

Effects of fetal antiepileptic drug exposure Outcomes at age 4.5 years

OBJECTIVE: To examine outcomes at age 4.5 years and compare to earlier ages in children with fetal antiepileptic drug (AED) exposure. METHODS: The NEAD Study is an ongoing prospective observational multicenter study, which enrolled pregnant women with epilepsy on AED monotherapy (1999–2004) to determine if differential long-term neurodevelopmental effects exist across 4 commonly used AEDs (carbamazepine, lamotrigine, phenytoin, or valproate). The primary outcome is IQ at 6 years of age. Planned analyses were conducted using Bayley Scales of Infant Development (BSID at age 2) and Differential Ability Scale (IQ at ages 3 and 4.5). RESULTS: Multivariate intent-to-treat (n = 310) and completer (n = 209) analyses of age 4.5 IQ revealed significant effects for AED group. IQ for children exposed to valproate was lower than each other AED. Adjusted means (95% confidence intervals) were carbamazepine 106 (102–109), lamotrigine 106 (102–109), phenytoin 105 (102–109), valproate 96 (91–100). IQ was negatively associated with valproate dose, but not other AEDs. Maternal IQ correlated with child IQ for children exposed to the other AEDs, but not valproate. Age 4.5 IQ correlated with age 2 BSID and age 3 IQ. Frequency of marked intellectual impairment diminished with age except for valproate (10% with IQ <70 at 4.5 years). Verbal abilities were impaired for all 4 AED groups compared to nonverbal skills. CONCLUSIONS: Adverse cognitive effects of fetal valproate exposure persist to 4.5 years and are related to performances at earlier ages. Verbal abilities may be impaired by commonly used AEDs. Additional research is needed

Lower atmosphere and pressure evolution on Pluto from ground-based stellar occultations, 1988-2016

Context. The tenuous nitrogen (N2) atmosphere on Pluto undergoes strong seasonal effects due to high obliquity and orbital eccentricity, and has recently (July 2015) been observed by the New Horizons spacecraft. Aims. The main goals of this study are (i) to construct a well calibrated record of the seasonal evolution of surface pressure on Pluto and (ii) to constrain the structure of the lower atmosphere using a central flash observed in 2015. Methods. Eleven stellar occultations by Pluto observed between 2002 and 2016 are used to retrieve atmospheric profiles (density, pressure, temperature) between altitude levels of ∼5 and ∼380 km (i.e. pressures from ∼10 μbar to 10 nbar). Results. (i) Pressure has suffered a monotonic increase from 1988 to 2016, that is compared to a seasonal volatile transport model, from which tight constraints on a combination of albedo and emissivity of N2 ice are derived. (ii) A central flash observed on 2015 June 29 is consistent with New Horizons REX profiles, provided that (a) large diurnal temperature variations (not expected by current models) occur over Sputnik Planitia; and/or (b) hazes with tangential optical depth of ∼0.3 are present at 4-7 km altitude levels; and/or (c) the nominal REX density values are overestimated by an implausibly large factor of ∼20%; and/or (d) higher terrains block part of the flash in the Charon facing hemisphere. © E. Meza et al. 2019

Behavioral Outcomes and Neurodevelopmental Disorders Among Children of Women With Epilepsy

IMPORTANCE The association of fetal exposure to antiseizure medications (ASMs) with outcomes in childhood are not well delineated. OBJECTIVE To examine the association of fetal ASM exposure with subsequent adaptive, behavioral or emotional, and neurodevelopmental disorder outcomes at 2, 3, and 4.5 years of age. DESIGN, SETTING, AND PARTICIPANTS The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational cohort study conducted at 20 epilepsy centers in the US. A total of 456 pregnant women with epilepsy or without epilepsy were enrolled from December 19, 2012, to January 13, 2016. Children of enrolled women were followed up with formal assessments at 2, 3, 4.5, and 6 years of age. Statistical analysis took place from August 2022 to May 2023. EXPOSURES Exposures included mother’s epilepsy status as well as mother’s ASM blood concentration in the third trimester (for children of women with epilepsy). Women with epilepsy were enrolled regardless of ASM regimen. MAIN OUTCOMES AND MEASURES The primary outcome was the Adaptive Behavior Assessment System, Third Edition (ABAS-3) General Adaptive Composite (GAC) score among children at 4.5 years of age. Children of women with epilepsy and children of women without epilepsy were compared, and the associations of ASM exposures with outcomes among exposed children were assessed. Secondary outcomes involved similar analyses of other related measures. RESULTS Primary analysis included 302 children of women with epilepsy (143 boys [47.4%]) and 84 children of women without epilepsy (45 boys [53.6%]). Overall adaptive functioning (ABAS-3 GAC score at 4.5 years) did not significantly differ between children of women with epilepsy and children of women without epilepsy (parameter estimate [PE], 0.4 [95% CI, −2.5 to 3.4]; P = .77). However, in adjusted analyses, a significant decrease in functioning was seen with increasing third-trimester maximum ASM blood concentrations (PE, −7.8 [95% CI, −12.6 to −3.1]; P = .001). This decrease in functioning was evident for levetiracetam (PE, −18.9 [95% CI, −26.8 to −10.9]; P < .001) and lamotrigine (PE, −12.0 [95% CI, −23.7 to −0.3]; P = .04), the ASMs with sample sizes large enough for analysis. Results were similar with third-trimester maximum daily dose. CONCLUSIONS AND RELEVANCE This study suggests that adaptive functioning of children of women with epilepsy taking commonly used ASMs did not significantly differ from that of children of women without epilepsy, but there was an exposure-dependent association of ASMs with functioning. Thus, psychiatric or psychological screening and referral of women with epilepsy and their offspring are recommended when appropriate. Additional research is needed to confirm these findings. © 2023 American Medical Association. All rights reserved.12 month embargo; first published 20 November 2023This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]