Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe

Genome-wide by Environment Interaction Studies of Depressive Symptoms and Psychosocial Stress in UK Biobank and Generation Scotland

Stress is associated with poorer physical and mental health. To improve our understanding of this link, we performed genome-wide association studies (GWAS) of depressive symptoms and genome-wide by environment interaction studies (GWEIS) of depressive symptoms and stressful life events (SLE) in two UK population-based cohorts (Generation Scotland and UK Biobank). No SNP was individually significant in either GWAS, but gene-based tests identified six genes associated with depressive symptoms in UK Biobank (DCC, ACSS3, DRD2, STAG1, FOXP2 and KYNU; p < 2.77 x 10(-6)). Two SNPs with genome-wide significant GxE effects were identified by GWEIS in Generation Scotland: rs12789145 (53-kb downstream PIWIL4; p = 4.95 x 10(-9); total SLE) and rs17070072 (intronic to ZCCHC2; p = 1.46 x 10(-8); dependent SLE). A third locus upstream CYLC2 (rs12000047 and rs12005200, p < 2.00 x 10(-8); dependent SLE) when the joint effect of the SNP main and GxE effects was considered. GWEIS gene-based tests identified: MTNR1B with GxE effect with dependent SLE in Generation Scotland; and PHF2 with the joint effect in UK Biobank (p < 2.77 x 10(-6)). Polygenic risk scores (PRSs) analyses incorporating GxE effects improved the prediction of depressive symptom scores, when using weights derived from either the UK Biobank GWAS of depressive symptoms (p = 0.01) or the PGC GWAS of major depressive disorder (p = 5.91 x 10(-3)). Using an independent sample, PRS derived using GWEIS GxE effects provided evidence of shared aetiologies between depressive symptoms and schizotypal personality, heart disease and COPD. Further such studies are required and may result in improved treatments for depression and other stress-related conditions

Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk

A century of trends in adult human height

Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5-22.7) and 16.5 cm (13.3-19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8-144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities 1,2 . This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity 3�6 . Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55 of the global rise in mean BMI from 1985 to 2017�and more than 80 in some low- and middle-income regions�was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing�and in some countries reversal�of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories. © 2019, The Author(s)

Chromosome variation in dividing protoplasts and cell suspensions of wheat

The cytology of bread wheat (Triticum aestivum) suspension lines, recycled lines (selected for high division frequency) and their dividing protoplasts, have been examined. Extensive numerical and structural chromosome variation was present in all the lines. The most frequently observed chromosome numbers were around 2n=32, indicating that considerable chromosome loss from the normal wheat complement (2n=6x=42) had occurred during selection of the lines. Chromosome aberrations also indicated loss of chromosome arms and chromosome segments. The implications of this variation for studies on transformation and for the potential regeneration of whole plants from protoplasts of bread wheat are discussed

Micorrizas arbusculares, poblaciones de microbios rizosféricos y actividades enzimáticas del suelo en huertos de cítricos bajo dos tipos de manejo de suelos sin labranza

The arbuscular mycorrhizal (AM) status [total AM colonization (RLT), percentage of root length with arbuscules (RLA) and vesicles (RLV), spore density and hyphal length density], microbial populations and soil enzyme activities were investigated in citrus (Satsuma Mandarin grafted on Poncirus trifoliata L. Raf) orchards. Two types of no-tillage soil management, natural grass cover and use of herbicides, were employed in these orchards. The citrus AM colonization (37.26-70.09%) was high in all the experimental orchards sampled. The highest RLA (43.83%), spore density (384.63 spores/100 g soil), hyphal length density (4.09 m g–1 soil), rhizospheric microbial populations and enzyme activities were observed in the orchards with a natural grass cover, and the lowest values, except urease activity, were found in the orchards treated with herbicides. Spore density, hyphal length density, catalase activity and phosphatase activity varied notably between no-tillage/natural grass and no-tillage/herbicides treated orchards in the soil layers above 40 cm. A correlation analysis showed that the hyphal length density and organic matter were significantly positively correlated. Soil enzyme activities, except phosphatase, were strongly correlated with the bacteria populations. The data presented here demonstrates that the RLA, spore density, hyphal length density, rhizospheric microbe populations and enzyme activities were significantly better in the soil layers above 40 cm of orchards with a natural grass cover than herbicidetreated soils. So, the establishment of a natural grass cover benefits soil quality in citrus orchards in Southern China.Se investig&oacute; en huertos de mandarino Satsuma injertado sobre Poncirus trifoliata L. Raf el estado de las micorrizas arbusculares (AM) [colonizaci&oacute;n total de AM (RLT), % de longitud de la ra&iacute;z con arb&uacute;sculos (RLA) y ves&iacute;culas (RLV), densidad de esporas y de hifas], las poblaciones microbianas y las actividades enzim&aacute;ticas del suelo. En estos huertos se emplea dos tipos de gesti&oacute;n del suelo sin labranza, uno mediante cubierta de c&eacute;sped natural y otro mediante uso de herbicidas. La colonizaci&oacute;n de AM en la ra&iacute;z de los c&iacute;tricos fue alta (37,26-70,09%) en todos los huertos muestreados. Se observ&oacute; el mayor RLA (43,83%), densidad de esporas (384,63 esporas/100 g de suelo), densidad de longitud de hifas (4,09 m g&ndash;1 de suelo), poblaciones microbianas rizosf&eacute;ricas y actividades enzim&aacute;ticas en los huertos con cubierta de c&eacute;sped natural. En las capas del suelo hasta los 40 cm, la densidad de las esporas y de las hifas, y la actividad de la catalasa y de la fosfatasa variaron notablemente entre los dos tratamientos. Un an&aacute;lisis de correlaci&oacute;n mostr&oacute; que la densidad de las hifas y la materia org&aacute;nica estaban significativamente correlacionadas. Las actividades enzim&aacute;ticas del suelo, a excepci&oacute;n de la fosfatasa, estuvieron fuertemente correlacionadas con las poblaciones de bacterias. Por lo tanto, la no labranza y el establecimiento de una cobertura de c&eacute;sped beneficia la calidad del suelo en estos huertos de c&iacute;tricos en el sur de China