Maternal adverse childhood experiences on child growth and development in rural Pakistan: An observational cohort study

Maternal adverse childhood experiences (ACEs) have significant impacts on the next generation with links to negative birth outcomes, impaired cognitive development, and increased socioemotional problems in children. However, not all types or levels of adversity are similarly deleterious and research from diverse contexts is needed to better understand why and how intergenerational transmission of adversity occurs. We examined the role of maternal ACEs on children’s growth, cognitive, and socioemotional development at 36 months postpartum in rural Pakistan. We used data from 877 mother-child dyads in the Bachpan Cohort, a birth cohort study. Maternal ACEs were captured using an adapted version of the ACE-International Questionnaire. Outcomes at 36 months of age included child growth using the WHO growth z-scores, fine motor and receptive language development assessed with the Bayley Scales of Infant and Toddler Development, and socioemotional and behavioral development measured with the Ages and Stages Questionnaire: Socioemotional and Strengths and Difficulties Questionnaire. To estimate the associations between maternal ACEs and child outcomes, we used multivariable generalized linear models with inverse probability weights to account for sampling and loss to follow-up. Over half of mothers in our sample (58%) experienced at least one ACE. Emotional abuse, physical abuse, and emotional neglect were the most commonly reported ACEs. We found null relationships between the number of maternal ACEs and child growth. Maternal ACEs were associated with higher fine motor and receptive language development and worse socioemotional and behavioral outcomes. Maternal ACE domains had similarly varying relationships with child outcomes. Our findings highlight the complexity of intergenerational associations between maternal ACEs and children’s growth and development. Further work is necessary to examine these relationships across cultural contexts and identify moderating factors to mitigate potential negative intergenerational effects

Tunable anisotropy in inverse opals and emerging optical properties

Using self-assembly, nanoscale materials can be fabricated from the bottom up. Opals and inverse opals are examples of self-assembled nanomaterials made from crystallizing colloidal particles. As self-assembly requires a high level of control, it is challenging to use building blocks with anisotropic geometry to form complex opals, which limits the realizable structures. Typically, spherical colloids are employed as building blocks, leading to symmetric, isotropic superstructures. However, a significantly richer palette of directionally dependent properties are expected if less symmetric, anisotropic structures can be created, especially originating from the assembly of regular, spherical particles. Here we show a simple method to introduce anisotropy into inverse opals by subjecting them to a post-assembly thermal treatment that results in directional shrinkage of the silica matrix caused by condensation of partially hydrated sol-gel silica structures. In this way, we can tailor the shape of the pores, and the anisotropy of the final inverse opal preserves the order and uniformity of the self-assembled structure, while completely avoiding the need to synthesize complex oval-shaped particles and crystallize them into such target geometries. Detailed X-ray photoelectron spectroscopy (XPS) and infrared (IR) spectroscopy studies clearly identify increasing degrees of sol-gel condensation in confinement as a mechanism for the structure change. A computer simulation of structure changes resulting from the condensation-induced shrinkage further confirmed this mechanism. As an example of property changes induced by the introduction of anisotropy, we characterized the optical spectra of the anisotropic inverse opals and found that the optical properties can be controlled in a precise way using calcination temperature

A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling

J. Kaprio, A. Palotie, A. Raevuori-Helkamaa ja S. Ripatti ovat työryhmän Eating Disorders Working Group of the Psychiatric Genomics Consortium jäseniä. Erratum in: Sci Rep. 2017 Aug 21;7(1):8379, doi: 10.1038/s41598-017-06409-3We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 x 10(-7); OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.Peer reviewe

A genome-wide association study of anorexia nervosa

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2,907 cases with AN from 14 countries (15 sites) and 14,860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01×10−7) in SOX2OT and rs17030795 (P=5.84×10−6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76×10−6) between CUL3 and FAM124B and rs1886797 (P=8.05×10−6) near SPATA13. Comparing discovery to replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P= 4×10−6), strongly suggesting that true findings exist but that our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field

Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202

Common Genetic Variation And Age at Onset Of Anorexia Nervosa

Background Genetics and biology may influence the age at onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to AN age at onset and to investigate the genetic associations between age at onset of AN and age at menarche. Methods A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed which included 9,335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age at onset, early-onset AN (< 13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses. Results Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (SNP-h2) were 0.01-0.04 for age at onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early- and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age at onset and early-onset AN estimated from independent GWASs significantly predicted age at onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early-onset AN. Conclusions Our results provide evidence consistent with a common variant genetic basis for age at onset and implicate biological pathways regulating menarche and reproduction.Peer reviewe

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe