Genome wide analysis of gene dosage in 24,092 individuals estimates that 10,000 genes modulate cognitive ability

International audienceGenomic copy number variants (CNVs) are routinely identified and reported back to patients with neuropsychiatric disorders, but their quantitative effects on essential traits such as cognitive ability are poorly documented. We have recently shown that the effect size of deletions on cognitive ability can be statistically predicted using measures of intolerance to haploinsufficiency. However, the effect sizes of duplications remain unknown. It is also unknown if the effect of multigenic CNVs are driven by a few genes intolerant to haploinsufficiency or distributed across tolerant genes as well. Here, we identified all CNVs > 50 kilobases in 24,092 individuals from unselected and autism cohorts with assessments of general intelligence. Statistical models used measures of intolerance to haploinsufficiency of genes included in CNVs to predict their effect size on intelligence. Intolerant genes decrease general intelligence by 0.8 and 2.6 points of intelligence quotient when duplicated or deleted, respectively. Effect sizes showed no heterogeneity across cohorts. Validation analyses demonstrated that models could predict CNV effect sizes with 78% accuracy. Data on the inheritance of 27,766 CNVs showed that deletions and duplications with the same effect size on intelligence occur de novo at the same frequency. We estimated that around 10,000 intolerant and tolerant genes negatively affect intelligence when deleted, and less than 2% have large effect sizes. Genes encompassed in CNVs were not enriched in any GOterms but gene regulation and brain expression were GOterms overrepresented in the intolerant subgroup. Such pervasive effects on cognition may be related to emergent properties of the genome not restricted to a limited number of biological pathways

Variation in referrals to secondary obstetrician-led care among primary midwifery care practices in the Netherlands: a nationwide cohort study

Contains fulltext : 154413.pdf (publisher's version ) (Open Access)BACKGROUND: The primary aim of this study was to describe the variation in intrapartum referral rates in midwifery practices in the Netherlands. Secondly, we wanted to explore the association between the practice referral rate and a woman's chance of an instrumental birth (caesarean section or vaginal instrumental birth). METHODS: We performed an observational study, using the Dutch national perinatal database. Low risk births in all primary care midwifery practices over the period 2008-2010 were selected. Intrapartum referral rates were calculated. The referral rate among nulliparous women was used to divide the practices in three tertile groups. In a multilevel logistic regression analysis the association between the referral rate and the chance of an instrumental birth was examined. RESULTS: The intrapartum referral rate varied from 9.7 to 63.7 percent (mean 37.8; SD 7.0), and for nulliparous women from 13.8 to 78.1 percent (mean 56.8; SD 8.4). The variation occurred predominantly in non-urgent referrals in the first stage of labour. In the practices in the lowest tertile group more nulliparous women had a spontaneous vaginal birth compared to the middle and highest tertile group (T1: 77.3%, T2:73.5%, T3: 72.0%). For multiparous women the spontaneous vaginal birth rate was 97%. Compared to the lowest tertile group the odds ratios for nulliparous women for an instrumental birth were 1.22 (CI 1.16-1.31) and 1.33 (CI 1.25-1.41) in the middle and high tertile groups. This association was no longer significant after controlling for obstetric interventions (pain relief or augmentation). CONCLUSIONS: The wide variation between referral rates may not be explained by medical factors or client characteristics alone. A high intrapartum referral rate in a midwifery practice is associated with an increased chance of an instrumental birth for nulliparous women, which is mediated by the increased use of obstetric interventions. Midwives should critically evaluate their referral behaviour. A high referral rate may indicate that more interventions are applied than necessary. This may lead to a lower chance of a spontaneous vaginal birth and a higher risk on a PPH. However, a low referral rate should not be achieved at the cost of perinatal safety

French ichthyological records for 2019

WOS:000715836000001International audienceUncommon fish records may reflect local or global changes of fish composition resulting from environmental changes or anthropog,enic activities. Significant records of uncommon marine fishes, including migrant, non-native, cryptic, rare and threatened species, collected in French waters or by French vessels in European waters, observed by scuba divers or beachgoers, are reported for the year 2019. They include first, new, rare and unusual records for the following 33 species: Tetronarce nobiliana, Gymnothorax unicolor, Maulisia mauli, Salmo trutta, Grammonus aler, Photostomias guernei, Ifintaia loppei, Echiodon drummondii, Holocentrus adscensionis, Nerophis lumbriciformis, Scorpaena scrofa, Lepidoirigla dieuzeidei, Eutelichthys leptochirus, Liparis montag tti, Mycteroperca rubra, Serranus cabrilla, Remora remora, Caram: crysos, Naucrates doctor, Trachurus picturatus, Seriola rivoliana, Argyrosomus regius, Parablennius pilicornis, Pseudoscopelus astronesthidens, Deltentosteus collonianus, Didogobius schlieweni, Didogobius splechinai, Gobius couchi, Gobius f.;asteveni, Lebetus guilleti, Synapturichthys kleinii, Lagocephalus lagocephalus and 21.1ola mola, among which I. loppei, H. adscensionis and P. astronesthidens represent first records for the French waters and additions to the Checklist of the marine fishes from metropolitan France. Photostomias guernei is a first record for the Bay of Biscay, found close the French ETV,