Food, nutrition, and autism: from soil to fork.

Food and nutrition-related factors have the potential to impact development of autism spectrum disorder (ASD) and quality of life for people with ASD, but gaps in evidence exist. On 10 November 2022, Tufts University's Friedman School of Nutrition Science and Policy and Food and Nutrition Innovation Institute hosted a 1-d meeting to explore the evidence and evidence gaps regarding the relationships of food and nutrition with ASD. This meeting report summarizes the presentations and deliberations from the meeting.

DNA methylation signatures as biomarkers of socioeconomic position.

This review article provides a framework for the use of deoxyribonucleic acid (DNA) methylation (DNAm) biomarkers to study the biological embedding of socioeconomic position (SEP) and summarizes the latest developments in the area. It presents the emerging literature showing associations between individual- and neighborhood-level SEP exposures and DNAm across the life course. In contrast to questionnaire-based methods of assessing SEP, we suggest that DNAm biomarkers may offer an accessible metric to study questions about SEP and health outcomes, acting as a personal dosimeter of exposure.

Prenatal vitamin intake in first month of pregnancy and DNA methylation in cord blood and placenta in two prospective cohorts.

Background: Prenatal vitamin use is recommended before and during pregnancies for normal fetal development. Prenatal vitamins do not have a standard formulation, but many contain calcium, folic acid, iodine, iron, omega-3 fatty acids, zinc, and vitamins A, B6, B12, and D, and usually they contain higher concentrations of folic acid and iron than regular multivitamins in the US Nutrient levels can impact epigenetic factors such as DNA methylation, but relationships between maternal prenatal vitamin use and DNA methylation have been relatively understudied. We examined use of prenatal vitamins in the first month of pregnancy in relation to cord blood and placenta DNA methylation in two prospective pregnancy cohorts: the Early Autism Risk Longitudinal Investigation (EARLI) and Markers of Autism Risk Learning Early Signs (MARBLES) studies.

Edited magnetic resonance spectroscopy in the neonatal brain.

J-difference-edited spectroscopy is a valuable approach for the detection of low-concentration metabolites with magnetic resonance spectroscopy (MRS). Currently, few edited MRS studies are performed in neonates due to suboptimal signal-to-noise ratio, relatively long acquisition times, and vulnerability to motion artifacts. Nonetheless, the technique presents an exciting opportunity in pediatric imaging research to study rapid maturational changes of neurotransmitter systems and other metabolic systems in early postnatal life.

Psychological distress among caregivers raising a child with autism spectrum disorder during the COVID-19 pandemic.

The COVID-19 pandemic may disproportionately impact parents of children with autism spectrum disorder (ASD). Loss of services and supports, heightened fears about increased infection rates, and disruption of daily routines likely adversely affect the well-being of children with ASD and their families. The goal of this study was to examine differences in psychological distress-as defined by symptoms of anxiety, depression, loneliness, and hyperarousal-between parents raising a child with ASD and parents in the US as a whole during the early stages of the pandemic (March-April 2020).

Maternal prepregnancy weight and gestational weight gain in association with autism and developmental disorders in offspring.

Objective: Maternal prepregnancy BMI and gestational weight gain (GWG) are examined in relation to autism spectrum disorder (ASD) and other developmental disorders (DD) in offspring in a multisite case-control study.

Methods: Maternal prepregnancy BMI, obtained from medical records or self-report, was categorized as underweight, normal weight, overweight, obesity Class 1, or obesity Class 2/3. GWG was standardized for gestational age (GWG z score), and the rate (pounds/week) was categorized per adherence with clinical recommendations.

Genome, Environment, Microbiome and Metabolome in Autism (GEMMA) Study Design: Biomarkers Identification for Precision Treatment and Primary Prevention of Autism Spectrum Disorders by an Integrated Multi-Omics Systems Biology Approach.

Autism Spectrum Disorder (ASD) affects approximately 1 child in 54, with a 35-fold increase since 1960. Selected studies suggest that part of the recent increase in prevalence is likely attributable to an improved awareness and recognition, and changes in clinical practice or service availability. However, this is not sufficient to explain this epidemiological phenomenon.

Cadmium, Smoking, and Human Blood DNA Methylation Profiles in Adults from the Strong Heart Study.

Background: The epigenetic effects of individual environmental toxicants in tobacco remain largely unexplored. Cadmium (Cd) has been associated with smoking-related health effects, and its concentration in tobacco smoke is higher in comparison with other metals.

Objectives: We studied the association of Cd and smoking exposures with human blood DNA methylation (DNAm) profiles.

Family history of immune conditions and autism spectrum and developmental disorders: Findings from the study to explore early development.

Numerous studies have reported immune system disturbances in individuals with autism and their family members; however, there is considerable variability in findings with respect to the specific immune conditions involved, their timing, and the family members affected and little understanding of variation by autism subphenotype. Using data from the Study to Explore Early Development (SEED), a multi-site case-control study of children born 2003-2006 in the United States, we examined the role of family history of autoimmune diseases, asthma, and allergies in autism spectrum disorder (ASD) as well as other developmental disorders (DD). We investigated maternal immune conditions during the pregnancy period, as well as lifetime history of these conditions in several family members (mother, father, siblings, and study child).

Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach.

Background: The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain.

Methods And Findings: We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings.

DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases.

Background: Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation.

Results: We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111).

Differences in testosterone and its precursors by sex of the offspring in meconium.

Prenatal metabolism exerts profound effects on development. The first stool of the newborn, meconium, provides a window into the prenatal metabolic environment. The objective of this study was to examine the feasibility of meconium as a novel matrix to quantify prenatal steroid levels.

Demographic profile of families and children in the Study to Explore Early Development (SEED): Case-control study of autism spectrum disorder.

Background: The Study to Explore Early Development (SEED) is designed to enhance knowledge of autism spectrum disorder characteristics and etiologies.

Objective: This paper describes the demographic profile of enrolled families and examines sociodemographic differences between children with autism spectrum disorder and children with other developmental problems or who are typically developing.

Methods: This multi-site case-control study used health, education, and birth certificate records to identify and enroll children aged 2-5 years into one of three groups: 1) cases (children with autism spectrum disorder), 2) developmental delay or disorder controls, or 3) general population controls.

Strategy to control type I error increases power to identify genetic variation using the full biological trajectory.

Genome-wide association studies have been successful in identifying loci that underlie continuous traits measured at a single time point. To additionally consider continuous traits longitudinally, it is desirable to look at SNP effects at baseline and over time using linear-mixed effects models. Estimation and interpretation of two coefficients in the same model raises concern regarding the optimal control of type I error.

Replication of an association of a common variant in the Reelin gene (RELN) with schizophrenia in Ashkenazi Jewish women.

A single nucleotide polymorphism (rs7341475) in RELN has recently been shown to be associated with schizophrenia (SZ) in an Ashkenazi Jewish (AJ) case--control study specifically in women by Shifman et al. We have replicated this association in women in another large independent Ashkenazi Jewish collection (721 cases, 259 female; 1455 controls, 834 female) and confirmed that it applies to both SZ and schizoaffective disorder. Furthermore, we explore the effects of this polymorphism through quantitative trait loci analysis of nine SZ related factors providing information on sex-specific genotype--phenotype correlations.

Inflammation and stress-related candidate genes, plasma interleukin-6 levels, and longevity in older adults.

Interleukin-6 (IL-6) is an inflammatory cytokine that influences the development of inflammatory and aging-related disorders and ultimately longevity. In order to study the influence of variants in genes that regulate inflammatory response on IL-6 levels and longevity, we screened a panel of 477 tag SNPs across 87 candidate genes in >5000 older participants from the population-based Cardiovascular Health Study (CHS). Baseline plasma IL-6 concentration was first confirmed as a strong predictor of all-cause mortality.

Haplotype block partitioning as a tool for dimensionality reduction in SNP association studies.

Background: Identification of disease-related genes in association studies is challenged by the large number of SNPs typed. To address the dilution of power caused by high dimensionality, and to generate results that are biologically interpretable, it is critical to take into consideration spatial correlation of SNPs along the genome. With the goal of identifying true genetic associations, partitioning the genome according to spatial correlation can be a powerful and meaningful way to address this dimensionality problem.

Association analysis indicates that a variant GATA-binding site in the PIK3CB promoter is a Cis-acting expression quantitative trait locus for this gene and attenuates insulin resistance in obese children.

Objective: In search of functional polymorphisms associated with the genetics of insulin resistance, we studied a variant in the promoter of PIK3CB, the gene coding for the catalytic p110beta subunit of phosphatidylinositol (PI) 3-kinase, a major effector of insulin action.

Research Design And Methods: The rs361072 C/T variant was selected among single nucleotide polymorphisms of the PIK3CB region because we suspected that its common C allele (allelic frequency approximately 50% in Europeans) could create a GATA-binding motif and was genotyped in five cohorts of obese (n = 1,876) and two cohorts of nonobese (n = 1,490) European children. To estimate insulin resistance in these children, the homeostasis model assessment for insulin resistance (HOMA-IR) index was measured in strict nutritional conditions.

Genome-wide linkage analysis of 723 affected relative pairs with late-onset Alzheimer's disease.

Previous attempts to identify genetic loci conferring risk for late-onset Alzheimer's disease (LOAD) through linkage analysis have observed some regions of linkage in common. However, due to the sometimes-considerable overlap between the samples, some of these reports cannot be considered to be independent replications. In order to assess the strength of the evidence for linkage and to obtain the best indication of the location of susceptibility genes, we have amalgamated three large samples to give a total of 723 affected relative pairs (ARPs).

Associations of classic Kaposi sarcoma with common variants in genes that modulate host immunity.

Classic Kaposi sarcoma (CKS) is an inflammatory-mediated neoplasm primarily caused by Kaposi sarcoma-associated herpesvirus (KSHV). Kaposi sarcoma lesions are characterized, in part, by the presence of proinflammatory cytokines and growth factors thought to regulate KSHV replication and CKS pathogenesis. Using genomic DNA extracted from 133 CKS cases and 172 KSHV-latent nuclear antigen-positive, population-based controls in Italy without HIV infection, we examined the risk of CKS associated with 28 common genetic variants in 14 immune-modulating genes.

Variation in the ciliary neurotrophic factor gene and muscle strength in older Caucasian women.

Objectives: To determine whether genetic variants in the ciliary neurotrophic factor (CNTF) gene are associated with muscle strength in older women.

Design: Cross-sectional analysis of baseline data from the Women's Health and Aging Studies I (1992) and II (1994), complementary population-based studies.

Setting: Twelve contiguous ZIP code areas in Baltimore, Maryland.

Use of susceptibility scoring in conjunction with the genotypic transmission disequilibrium test.

We explored the utility of selecting a genetically predisposed subgroup to increase the finding of a genetic signal in the Genetic Analysis Workshop 14 Collaborative Study on the Genetics of Alcoholism dataset. A subgroup of affected probands with low environmental risk exposures was defined using a susceptibility score calculated from an environmental risk model. Thirty-nine probands with highly positive scores were selected, along with their parents, for use in a genotypic transmission disequilibrium test (TDT) test.

IL-6 gene variation is not associated with increased serum levels of IL-6, muscle, weakness, or frailty in older women.

Elevated levels of the inflammatory cytokine IL-6 are associated with the development of disability, frailty, and mortality in older adults. These outcomes are likely mediated through inflammatory activity that alters hormones, skeletal muscle, and the immune system. Polymorphic variants in the IL-6 gene influence IL-6 expression.