An exploration into the causal relationships between educational attainment, intelligence, and wellbeing: an observational and two-sample Mendelian randomisation study.

Educational attainment is associated with a range of positive outcomes, yet its impact on wellbeing is unclear, and complicated by high correlations with intelligence. We use genetic and observational data to investigate for the first time, whether educational attainment and intelligence are causally and independently related to wellbeing. Results from our multivariable Mendelian randomisation demonstrated a positive causal impact of a genetic predisposition to higher educational attainment on wellbeing that remained after accounting for intelligence, and a negative impact of intelligence that was independent of educational attainment. Observational analyses suggested that these associations may be subject to sex differences, with benefits to wellbeing greater for females who attend higher education compared to males. For intelligence, males scoring more highly on measures related to happiness were those with lower intelligence. Our findings demonstrate a unique benefit for wellbeing of staying in school, over and above improving cognitive abilities, with benefits likely to be greater for females compared to males.

Respectful Maternity Care : A Systematic Review.

BACKGROUND: Severe maternal morbidity and mortality are worse in the United States than in all similar countries, with the greatest effect on Black women. Emerging research suggests that disrespectful care during childbirth contributes to this problem. PURPOSE: To conduct a systematic review on definitions and valid measurements of respectful maternity care (RMC), its effectiveness for improving maternal and infant health outcomes for those who are pregnant and postpartum, and strategies for implementation. DATA SOURCES: Systematic searches of Ovid Medline, CINAHL, Embase, Cochrane Central Register of Controlled Trials, PsycInfo, and SocINDEX for English-language studies (inception to July 2023). STUDY SELECTION: Randomized controlled trials and nonrandomized studies of interventions of RMC versus usual care for effectiveness studies; additional qualitative and noncomparative validation studies for definitions and measurement studies. DATA EXTRACTION: Dual data abstraction and quality assessment using established methods, with resolution of disagreements through consensus. DATA SYNTHESIS: Thirty-seven studies were included across all questions, of which 1 provided insufficient evidence on the effectiveness of RMC to improve maternal outcomes and none studied RMC to improve infant outcomes. To define RMC, authors identified 12 RMC frameworks, from which 2 main concepts were identified: disrespect and abuse and rights-based frameworks. Disrespect and abuse components focused on recognizing birth mistreatment; rights-based frameworks incorporated aspects of reproductive justice, human rights, and antiracism. Five overlapping framework themes include freedom from abuse, consent, privacy, dignity, communication, safety, and justice. Twelve tools to measure RMC were validated in 24 studies on content validity, construct validity, and internal consistency, but lack of a gold standard limited evaluation of criterion validity. Three tools specific for RMC had at least 1 study demonstrating consistency internally and with an intended construct relevant to U.S. settings, but no single tool stands out as the best measure of RMC. LIMITATIONS: No studies evaluated other health outcomes or RMC implementation strategies. The lack of definition and gold standard limit evaluation of RMC tools. CONCLUSION: Frameworks for RMC are well described but vary in their definitions. Tools to measure RMC demonstrate consistency but lack a gold standard, requiring further evaluation before implementation in U.S. settings. Evidence is lacking on the effectiveness of implementing RMC to improve any maternal or infant health outcome. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42023394769).

Under-Triage and Over-Triage Using the Field Triage Guidelines for Injured Patients: A Systematic Review.

OBJECTIVES: The Field Triage Guidelines (FTG) are used across North America to identify seriously injured patients for transport to appropriate level trauma centers, with a goal of under-triaging no more than 5% and over-triaging between 25% and 35%. Our objective was to systematically review the literature on under-triage and over-triage rates of the FTG. METHODS: We conducted a systematic review of the FTG performance. Ovid Medline, EMBASE, and the Cochrane databases were searched for studies published between January 2011 and February 2021. Two investigators dual-reviewed eligibility of abstracts and full-text. We included studies evaluating under- or over-triage of patients using the FTG in the prehospital setting. We excluded studies not reporting an outcome of under- or over-triage, studies evaluating other triage tools, or studies of triage not in the prehospital setting. Two investigators independently assessed the risk of bias for each included article. The primary accuracy measures to assess the FTG were under-triage, defined as seriously injured patients transported to non-trauma hospitals (1-sensitivity), and over-triage, defined as non-injured patients transported to trauma hospitals (1-specificity). Due to heterogeneity, results were synthesized qualitatively. RESULTS: We screened 2,418 abstracts, reviewed 315 full-text publications, and identified 17 studies that evaluated the accuracy of the FTG. Among eight studies evaluating the entire FTG (steps 1-4), under-triage rates ranged from 1.6% to 72.0% and were higher for older (≥55 or ≥65 years) adults (20.1-72.0%) and pediatric (<15 years) patients (15.9-34.8%) compared to all ages (1.6-33.8%). Over-triage rates ranged from 9.9% to 87.4% and were higher for all ages (12.2-87.4%) compared to older (≥55 or ≥65 years) adults (9.9-48.2%) and pediatric (<15 years) patients (28.0-33.6%). Under-triage was lower in studies strictly applying the FTG retrospectively (1.6-34.8%) compared to as-practiced (10.5-72.0%), while over-triage was higher retrospectively (64.2-87.4%) compared to as-practiced (9.9-48.2%). CONCLUSIONS: Evidence suggests that under-triage, while improved if the FTG is strictly applied, remains above targets, with higher rates of under-triage in both children and older adults.

Telehealth-guided provider-to-provider communication to improve rural health: A systematic review.

INTRODUCTION: Telehealth may address healthcare disparities for rural populations. This systematic review assesses the use, effectiveness, and implementation of telehealth-supported provider-to-provider collaboration to improve rural healthcare. METHODS: We searched Ovid MEDLINE®, CINAHL®, EMBASE, and Cochrane CENTRAL from 1 January 2010 to 12 October 2021 for trials and observational studies of rural provider-to-provider telehealth. Abstracts and full text were dual-reviewed. We assessed the risk of bias for individual studies and strength of evidence for studies with similar outcomes. RESULTS: Seven studies of rural uptake of provider-to-provider telehealth documented increases over time but variability across geographic regions. In 97 effectiveness studies, outcomes were similar with rural provider-to-provider telehealth versus without for inpatient consultations, neonatal care, outpatient depression and diabetes, and emergency care. Better or similar results were reported for changes in rural clinician behavior, knowledge, confidence, and self-efficacy. Evidence was insufficient for other clinical uses and outcomes. Sixty-seven (67) evaluation and qualitative studies identified barriers and facilitators to implementing rural provider-to-provider telehealth. Success was linked to well-functioning technology, sufficient resources, and adequate payment. Barriers included lack of understanding of rural context and resources. Methodologic weaknesses of studies included less rigorous study designs and small samples. DISCUSSION: Rural provider-to-provider telehealth produces similar or better results versus care without telehealth. Barriers to rural provider-to-provider telehealth implementation are common to practice change but include some specific to rural adaptation and adoption. Evidence gaps are partially due to studies that do not address differences in the groups compared or do not include sufficient sample sizes.

Mechanism of injury and special considerations as predictive of serious injury: A systematic review.

OBJECTIVES: The Centers for Disease Control and Prevention's field triage guidelines (FTG) are routinely used by emergency medical services personnel for triaging injured patients. The most recent (2011) FTG contains physiologic, anatomic, mechanism, and special consideration steps. Our objective was to systematically review the criteria in the mechanism and special consideration steps that might be predictive of serious injury or need for a trauma center. METHODS: We conducted a systematic review of the predictive utility of mechanism and special consideration criteria for predicting serious injury. A research librarian searched in Ovid Medline, EMBASE, and the Cochrane databases for studies published between January 2011 and February 2021. Eligible studies were identified using a priori inclusion and exclusion criteria. Studies were excluded if they lacked an outcome for serious injury, such as measures of resource use, injury severity scores, mortality, or composite measures using a combination of outcomes. Given the heterogeneity in populations, measures, and outcomes, results were synthesized qualitatively focusing on positive likelihood ratios (LR+) whenever these could be calculated from presented data or adjusted odds ratios (aOR). RESULTS: We reviewed 2418 abstracts and 315 full-text publications and identified 42 relevant studies. The factors most predictive of serious injury across multiple studies were death in the same vehicle (LR+ 2.2-7.4), ejection (aOR 3.2-266.2), extrication (LR+ 1.1-6.6), lack of seat belt use (aOR 4.4-11.3), high speeds (aOR 2.0-2.9), concerning crash variables identified by vehicle telemetry systems (LR+ 4.7-22.2), falls from height (LR+ 2.4-5.9), and axial load or diving (aOR 2.5-17.6). Minor or inconsistent predictors of serious injury were vehicle intrusion (LR+ 0.8-7.2), cardiopulmonary or neurologic comorbidities (LR+ 0.8-3.1), older age (LR+ 0.6-6.8), or anticoagulant use (LR+ 1.1-1.8). CONCLUSIONS: Select mechanism and special consideration criteria contribute positively to appropriate field triage of potentially injured patients.

Prehospital Airway Management: A Systematic Review.

Objective: To assess comparative benefits and harms across three airway management approaches (bag valve mask [BVM], supraglottic airway [SGA], and endotracheal intubation [ETI]) used by prehospital emergency medical services (EMS) to treat patients with trauma, cardiac arrest, or medical emergencies, and how they differ based on techniques and devices, EMS personnel and patient characteristics. Data sources: We searched electronic citation databases (Ovid® MEDLINE®, CINAHL®, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus®) from 1990 to September 2020. Review methods: We followed Agency for Healthcare Research and Quality Effective Health Care Program Methods guidance. Outcomes included mortality, neurological function, return of spontaneous circulation (ROSC), and successful advanced airway insertion. Meta-analyses using profile-likelihood random effects models were conducted, with analyses stratified by study design, emergency type, and age. Results: We included 99 studies involving 630,397 patients. We found few differences in primary outcomes across airway management approaches. For survival, there was no difference for BVM versus ETI or SGA in adult and pediatric patients with cardiac arrest or trauma. For neurological function, there was no difference for BVM versus ETI and SGA versus ETI in pediatric patients with cardiac arrest. There was no difference in BVM versus ETI in adults with cardiac arrest, but improved neurological function with BVM or ETI versus SGA. There was no difference in ROSC for patients with cardiac arrest for BVM versus ETI or SGA in adults and pediatrics, or SGA versus ETI in pediatrics. There was higher frequency of ROSC in adults with SGA versus ETI. For successful advanced airway insertion, there was higher first-pass success with SGA versus ETI for all patients except adult medical patients (no difference), and no difference in overall success using SGA versus ETI in adults. Conclusions: The currently available evidence does not indicate benefits of more invasive airway approaches based on survival, neurological function, ROSC, or successful airway insertion. Strength of evidence was low or moderate; most included studies were observational. This supports the need for high-quality randomized controlled trials to advance clinical practice and EMS education and policy, and improve patient-centered outcomes.

Reproductive outcomes of women aged 40 and older undergoing IVF with donor sperm.

STUDY QUESTION: Do women ≥40 years old without a male partner who utilize donor sperm have the same reproductive outcomes as those who utilize their partner's sperm? SUMMARY ANSWER: After controlling for relevant confounders, women ≥40 years old using donor sperm for IVF have significantly higher odds of having a live birth compared to those utilizing their partner's sperm. WHAT IS KNOWN ALREADY: Women who are unpartnered or in same-sex relationships are by definition not infertile, but may choose to conceive using donor sperm. It is not known how IVF outcomes are affected with the use of donor sperm compared to women utilizing their partner's sperm, particularly at very advanced maternal ages. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study conducted at a university-affiliated center of women undergoing IVF with fresh embryo transfer between 2008 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were divided into two groups based on the ejaculated sperm source utilized: donor or partner sperm. Live birth rate was the primary outcome. Pregnancy rate was the secondary outcome. Multivariable logistic regression was performed and adjusted for age, the developmental stage of the embryo, and the number of embryos transferred. Unadjusted odds ratio (OR) and adjusted OR (aOR) with 95% CI for pregnancy and live birth were estimated. Statistical significance was denoted by P < 0.05. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 3910 cycles in women ≥40 years old were analyzed, of which 307 utilized donor sperm and 3603 utilized their partner's sperm to conceive. In the univariate analysis, patients utilizing donor sperm were found to have similar pregnancy rates as those utilizing partner sperm (41.0 vs 39.8%, OR: 0.95, 95% CI: 0.75-1.20). After adjusting for age, the number of embryos transferred and the developmental stage of the embryos, the model estimates did not vary (aOR: 1.22, 95% CI: 0.95-1.56). Similarly, the univariate analysis for live birth did not demonstrate a difference between groups (19.2 vs 17.8%, OR: 0.91, 95% CI: 0.67-1.22). However, after a similar adjustment was made for confounders, the use of donor sperm was associated with statistically significant increased odds of live birth (aOR: 1.38, 95% CI: 1.01-1.88). LIMITATIONS, REASONS FOR CAUTION: As with any retrospective study, the potential for residual confounding exists, despite attempts to control for this with regression modeling. WIDER IMPLICATIONS OF THE FINDINGS: Women ≥40 years old who are unpartnered or in same-sex relationships can be counseled that their odds of a live birth are slightly better than women in heterosexual relationships utilizing their partner's sperm. These findings serve to further refine and individualize counseling on the expected IVF outcomes for women in this population. STUDY FUNDING/COMPETING INTEREST(S): No funding was sought for this study. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Guidelines for the Management of Pediatric Severe Traumatic Brain Injury, Third Edition: Update of the Brain Trauma Foundation Guidelines, Executive Summary.

OBJECTIVES: The purpose of this work is to identify and synthesize research produced since the second edition of these Guidelines was published and incorporate new results into revised evidence-based recommendations for the treatment of severe traumatic brain injury in pediatric patients. METHODS AND MAIN RESULTS: This document provides an overview of our process, lists the new research added, and includes the revised recommendations. Recommendations are only provided when there is supporting evidence. This update includes 22 recommendations, nine are new or revised from previous editions. New recommendations on neuroimaging, hyperosmolar therapy, analgesics and sedatives, seizure prophylaxis, temperature control/hypothermia, and nutrition are provided. None are level I, three are level II, and 19 are level III. The Clinical Investigators responsible for these Guidelines also created a companion algorithm that supplements the recommendations with expert consensus where evidence is not available and organizes possible interventions into first and second tier utilization. The purpose of publishing the algorithm as a separate document is to provide guidance for clinicians while maintaining a clear distinction between what is evidence based and what is consensus based. This approach allows, and is intended to encourage, continued creativity in treatment and research where evidence is lacking. Additionally, it allows for the use of the evidence-based recommendations as the foundation for other pathways, protocols, or algorithms specific to different organizations or environments. The complete guideline document and supplemental appendices are available electronically from this journal. These documents contain summaries and evaluations of all the studies considered, including those from prior editions, and more detailed information on our methodology. CONCLUSIONS: New level II and level III evidence-based recommendations and an algorithm provide additional guidance for the development of local protocols to treat pediatric patients with severe traumatic brain injury. Our intention is to identify and institute a sustainable process to update these Guidelines as new evidence becomes available.

Guidelines for the Management of Pediatric Severe Traumatic Brain Injury, Third Edition: Update of the Brain Trauma Foundation Guidelines, Executive Summary.

The purpose of this work is to identify and synthesize research produced since the second edition of these Guidelines was published and incorporate new results into revised evidence-based recommendations for the treatment of severe traumatic brain injury in pediatric patients. This document provides an overview of our process, lists the new research added, and includes the revised recommendations. Recommendations are only provided when there is supporting evidence. This update includes 22 recommendations, 9 are new or revised from previous editions. New recommendations on neuroimaging, hyperosmolar therapy, analgesics and sedatives, seizure prophylaxis, temperature control/hypothermia, and nutrition are provided. None are level I, 3 are level II, and 19 are level III. The Clinical Investigators responsible for these Guidelines also created a companion algorithm that supplements the recommendations with expert consensus where evidence is not available and organizes possible interventions into first and second tier utilization. The complete guideline document and supplemental appendices are available electronically (https://doi.org/10.1097/PCC.0000000000001735). The online documents contain summaries and evaluations of all the studies considered, including those from prior editions, and more detailed information on our methodology. New level II and level III evidence-based recommendations and an algorithm provide additional guidance for the development of local protocols to treat pediatric patients with severe traumatic brain injury. Our intention is to identify and institute a sustainable process to update these Guidelines as new evidence becomes available.

Management of Suspected Opioid Overdose With Naloxone in Out-of-Hospital Settings: A Systematic Review.

BACKGROUND: Naloxone is effective for reversing opioid overdose, but optimal strategies for out-of-hospital use are uncertain. PURPOSE: To synthesize evidence on 1) the effects of naloxone route of administration and dosing for suspected opioid overdose in out-of-hospital settings on mortality, reversal of overdose, and harms, and 2) the need for transport to a health care facility after reversal of overdose with naloxone. DATA SOURCES: Ovid MEDLINE (1946 through September 2017), PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL, U.S. Food and Drug Administration (FDA) materials, and reference lists. STUDY SELECTION: English-language cohort studies and randomized trials that compared different doses of naloxone, administration routes, or transport versus nontransport after reversal of overdose with naloxone. Main outcomes were mortality, reversal of overdose, recurrence of overdose, and harms. DATA EXTRACTION: Dual extraction and quality assessment of individual studies; consensus assessment of overall strength of evidence (SOE). DATA SYNTHESIS: Of 13 eligible studies, 3 randomized controlled trials and 4 cohort studies compared different administration routes. At the same dose (2 mg), 1 trial found similar efficacy between higher-concentration intranasal naloxone (2 mg/mL) and intramuscular naloxone, and 1 trial found that lower-concentration intranasal naloxone (2 mg/5 mL) was less effective than intramuscular naloxone but was associated with decreased risk for agitation (low SOE). Evidence was insufficient to evaluate other comparisons of route of administration. Six uncontrolled studies reported low rates of death and serious adverse events (0% to 1.25%) in nontransported patients after successful naloxone treatment. LIMITATION: There were few studies, all had methodological limitations, and none evaluated FDA-approved autoinjectors or highly concentrated intranasal formulations. CONCLUSION: Higher-concentration intranasal naloxone (2 mg/mL) seems to have efficacy similar to that of intramuscular naloxone for reversal of opioid overdose, with no difference in adverse events. Nontransport after reversal of overdose with naloxone seems to be associated with a low rate of serious harms, but no study evaluated risks of transport versus nontransport. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42016053891).

Retrenched Welfare Regimes Still Lessen Social Class Inequalities in Health: A Longitudinal Analysis of the 2003-2010 EU-SILC in 23 European Countries.

This article builds on recent work that has explored how welfare regimes moderate social class inequalities in health. It extends research to date by using longitudinal data from the EU-SILC (2003-2010) and examines how the relationship between social class and self-reported health and chronic conditions varies across 23 countries, which are split into five welfare regimes (Nordic, Anglo-Saxon, Eastern, Southern, and Continental). Our analysis finds that health across all classes was only worse in Eastern Europe (compared with the Nordic countries). In contrast, we find evidence that the social class gradient in both measures of health was significantly wider in the Anglo-Saxon and Southern regimes. We suggest that this evidence supports the notion that welfare regimes continue to explain differences in health according to social class location. We therefore argue that although downward pressures from globalization and neoliberalism have blurred welfare regime typologies, the Nordic model may continue to have an important mediating effect on class-based inequalities in health.

Historical versus contemporary medicinal plant uses in the US Virgin Islands.

ETHNOPHARMACOLOGICAL RELEVANCE: Hidden in the documents of the dark past of the trans-Atlantic slavery are gems of ethnomedicinal observations, supported by herbarium specimens, which tell of the traditional medicine of a by-gone slave society in the Caribbean. In the context of the former Danish West Indies (now US Virgin Islands), we identify pre-1900 medicinal plants and their historical uses, and trace their status in the traditional medicine of St. Croix today (2014). By a combined historical and ethnobotanical approach we assess the scale of loss and preservation of traditional medicinal knowledge on St. Croix, and explore the drivers involved in the disappearance of knowledge in the oral tradition of medicine. MATERIALS AND METHODS: Names, uses and identities of 18th and 19th century medicinal plant uses in the Danish West Indies were derived from manuscripts and publications of Von Rohr (1757/58), Oldendorp (1777), West (1793), Benzon (1822), Riise (1853), Eggers (1876;1879) and Berg and Eggers (1888). The presence of the plant species in the pre-1900 Danish West Indies was confirmed by review of herbarium specimens in the University of Copenhagen Herbarium (C). The same species were collected on St. Croix in 2014 or their ecological status discussed with local specialists. Semi-structured interviews supported by photographs and specimens were conducted with six medicinal plant specialist on St. Croix, to document and compare contemporary names and uses of the historically used medicinal plants. RESULTS AND DISCUSSION: The historic ethnomedicinal sources revealed 102 medicinal uses of 64 plant species. Thirty-eight (37%) of the pre-1900 medicinal uses were traced in interviews, while sixty-four uses (63%) appear to be forgotten, discontinued or otherwise lost. Thirteen species appear to have entirely lost their status as medicinal plants on St. Croix, while 32 species (50%) have lost uses while retaining or gaining others. While 20% of the lost medicinal plant uses can be explained by biodiversity loss, and others likely have become obsolete due to advances in public health and scientific medicine, 33 of the 64 lost medicinal uses of non-rare species uses fall in the same categories as the preserved uses (fever, stomach, wound, laxative, pulmonary, intestinal, pain, anthelmintic, blood purifier, eye-inflammation). We therefore argue that at least half of the known pre-1900 medicinal plant uses have become culturally extinct for other reasons than to biodiversity loss or modern obsoleteness. CONCLUSIONS: The present study utilized knowledge from an oral medicinal tradition, documented in the context of a colonial society. Without doubt, basis for further similar studies exists in the more or less accessible archives, herbaria and collections of former colonial powers. Such studies could directly benefit the descendants of the original intellectual property holders culturally and economically, or serve as stepping stones to integrate, or re-integrate, lost medicinal plant uses in both local and wider evidence-based contexts.

Heritability and genome-wide analyses of problematic peer relationships during childhood and adolescence.

Peer behaviour plays an important role in the development of social adjustment, though little is known about its genetic architecture. We conducted a twin study combined with a genome-wide complex trait analysis (GCTA) and a genome-wide screen to characterise genetic influences on problematic peer behaviour during childhood and adolescence. This included a series of longitudinal measures (parent-reported Strengths-and-Difficulties Questionnaire) from a UK population-based birth-cohort (ALSPAC, 4-17 years), and a UK twin sample (TEDS, 4-11 years). Longitudinal twin analysis (TEDS; N ≤ 7,366 twin pairs) showed that peer problems in childhood are heritable (4-11 years, 0.60 < twin-h(2) ≤ 0.71) but genetically heterogeneous from age to age (4-11 years, twin-r(g) = 0.30). GCTA (ALSPAC: N ≤ 5,608, TEDS: N ≤ 2,691) provided furthermore little support for the contribution of measured common genetic variants during childhood (4-12 years, 0.02 < GCTA-h(2)(Meta) ≤ 0.11) though these influences become stronger in adolescence (13-17 years, 0.14 < GCTA-h (2)(ALSPAC) ≤ 0.27). A subsequent cross-sectional genome-wide screen in ALSPAC (N ≤ 6,000) focussed on peer problems with the highest GCTA-heritability (10, 13 and 17 years, 0.0002 < GCTA-P ≤ 0.03). Single variant signals (P ≤ 10(-5)) were followed up in TEDS (N ≤ 2835, 9 and 11 years) and, in search for autism quantitative trait loci, explored within two autism samples (AGRE: N Pedigrees = 793; ACC: N Cases = 1,453/N Controls = 7,070). There was, however, no evidence for association in TEDS and little evidence for an overlap with the autistic continuum. In summary, our findings suggest that problematic peer relationships are heritable but genetically complex and heterogeneous from age to age, with an increase in common measurable genetic variation during adolescence.

Childhood intelligence is heritable, highly polygenic and associated with FNBP1L.

Intelligence in childhood, as measured by psychometric cognitive tests, is a strong predictor of many important life outcomes, including educational attainment, income, health and lifespan. Results from twin, family and adoption studies are consistent with general intelligence being highly heritable and genetically stable throughout the life course. No robustly associated genetic loci or variants for childhood intelligence have been reported. Here, we report the first genome-wide association study (GWAS) on childhood intelligence (age range 6-18 years) from 17,989 individuals in six discovery and three replication samples. Although no individual single-nucleotide polymorphisms (SNPs) were detected with genome-wide significance, we show that the aggregate effects of common SNPs explain 22-46% of phenotypic variation in childhood intelligence in the three largest cohorts (P=3.9 × 10(-15), 0.014 and 0.028). FNBP1L, previously reported to be the most significantly associated gene for adult intelligence, was also significantly associated with childhood intelligence (P=0.003). Polygenic prediction analyses resulted in a significant correlation between predictor and outcome in all replication cohorts. The proportion of childhood intelligence explained by the predictor reached 1.2% (P=6 × 10(-5)), 3.5% (P=10(-3)) and 0.5% (P=6 × 10(-5)) in three independent validation cohorts. Given the sample sizes, these genetic prediction results are consistent with expectations if the genetic architecture of childhood intelligence is like that of body mass index or height. Our study provides molecular support for the heritability and polygenic nature of childhood intelligence. Larger sample sizes will be required to detect individual variants with genome-wide significance.

A common variant in myosin-18B contributes to mathematical abilities in children with dyslexia and intraparietal sulcus variability in adults.

The ability to perform mathematical tasks is required in everyday life. Although heritability estimates suggest a genetic contribution, no previous study has conclusively identified a genetic risk variant for mathematical performance. Research has shown that the prevalence of mathematical disabilities is increased in children with dyslexia. We therefore correlated genome-wide data of 200 German children with spelling disability, with available quantitative data on mathematic ability. Replication of the top findings in additional dyslexia samples revealed that rs133885 was a genome-wide significant marker for mathematical abilities (P(comb) = 7.71 × 10(-10), n = 699), with an effect size of 4.87%. This association was also found in a sample from the general population (P = 0.048, n = 1080), albeit with a lower effect size. The identified variant encodes an amino-acid substitution in MYO18B, a protein with as yet unknown functions in the brain. As areas of the parietal cortex, in particular the intraparietal sulcus (IPS), are involved in numerical processing in humans, we investigated whether rs133885 was associated with IPS morphology using structural magnetic resonance imaging data from 79 neuropsychiatrically healthy adults. Carriers of the MYO18B risk-genotype displayed a significantly lower depth of the right IPS. This validates the identified association between rs133885 and mathematical disability at the level of a specific intermediate phenotype.

Visual analysis of geocoded twin data puts nature and nurture on the map.

Twin studies allow us to estimate the relative contributions of nature and nurture to human phenotypes by comparing the resemblance of identical and fraternal twins. Variation in complex traits is a balance of genetic and environmental influences; these influences are typically estimated at a population level. However, what if the balance of nature and nurture varies depending on where we grow up? Here we use statistical and visual analysis of geocoded data from over 6700 families to show that genetic and environmental contributions to 45 childhood cognitive and behavioral phenotypes vary geographically in the United Kingdom. This has implications for detecting environmental exposures that may interact with the genetic influences on complex traits, and for the statistical power of samples recruited for genetic association studies. More broadly, our experience demonstrates the potential for collaborative exploratory visualization to act as a lingua franca for large-scale interdisciplinary research.