Dietary Intake Mendelian Randomization: Assessment and Development of Methods for Instrument Selection and Robust Inference.

Background: Mendelian randomization (MR) uses genetic instruments (GI) to infer causality between exposures, like dietary intake, and health outcomes. Almost all MR of dietary intake use the full set of genome-wide significant (GWS) variants in the GI, and therefore, causal estimates are likely biased by variants that act indirectly on diet.

Objective: First, we performed an assessment of the diet MR literature to evaluate the applications and approaches common in the field.

Network-based representation learning reveals the impact of age and diet on the gut microbial and metabolomic environment of U.S. infants in a randomized controlled feeding trial.

While studies have explored differences in gut microbiome development for infant liquid diets (breastmilk, formula), little is known about the impact of complementary foods on infant gut microbiome development. Here, we investigated how different protein-rich foods (i.e.

Global multi-ancestry genetic study elucidates genes and biological pathways associated with thyroid cancer and benign thyroid diseases.

Thyroid diseases are common and highly heritable. Under the Global Biobank Meta-analysis Initiative, we performed a meta-analysis of genome-wide association studies from 19 biobanks for five thyroid diseases: thyroid cancer, benign nodular goiter, Graves' disease, lymphocytic thyroiditis, and primary hypothyroidism. We analyzed genetic association data from ~2.

Characterization of astaxanthin isomers in different types of salmon filets and human plasma after salmon consumption.

Astaxanthin, a marine carotenoid with antioxidant and anti-inflammatory properties, exists in various isomers in salmon. Despite salmon being a key dietary source of astaxanthin in American diets, the isomer contents across salmon types, processing methods, and human plasma post-consumption remains underexplored. Using mass spectrometry, we analyzed astaxanthin isomers, EPA, and DHA in wild and farmed salmon, processed salmon products, and human plasma following a feeding study.

Epigenome-wide association study meta-analysis of BMI in African American Adults.

Despite considerable advances in identifying risk factors for obesity development, there remains substantial gaps in our knowledge about its etiology. Variation in obesity (defined by BMI) is thought to be due in part to heritable factors; however, obesity-associated genetic variants only account for a small portion of heritability. Epigenetic regulation defined by genetic and/or environmental factors with changes in gene expression, may account for some of this "missing heritability".

Characterizing substructure via mixture modeling in large-scale genetic summary statistics.

Genetic summary data are broadly accessible and highly useful, including for risk prediction, causal inference, fine mapping, and incorporation of external controls. However, collapsing individual-level data into summary data, such as allele frequencies, masks intra- and inter-sample heterogeneity, leading to confounding, reduced power, and bias. Ultimately, unaccounted-for substructure limits summary data usability, especially for understudied or admixed populations.

CCAFE: Estimating Case and Control Allele Frequencies from GWAS Summary Statistics.

Methods involving summary statistics in genetics can be quite powerful but can be limited in utility. For instance, many post-hoc analyses of disease studies require case and control allele frequencies (AFs), which are not always published. We present two frameworks to derive case and control AFs from GWAS summary statistics using the odds ratio, case and control sample sizes, and either the total (case and control aggregated) AF or standard error (SE).

Characterizing substructure via mixture modeling in large-scale genetic summary statistics.

Genetic summary data are broadly accessible and highly useful including for risk prediction, causal inference, fine mapping, and incorporation of external controls. However, collapsing individual-level data into groups masks intra- and inter-sample heterogeneity, leading to confounding, reduced power, and bias. Ultimately, unaccounted substructure limits summary data usability, especially for understudied or admixed populations.

Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial.

Background: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited.

Objectives: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry.

Methods: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3).

mini-MED: study protocol for a randomized, multi-intervention, semi-controlled feeding trial of a Mediterranean-amplified vs. habitual Western dietary pattern for the evaluation of food-specific compounds and cardiometabolic health.

Background: Diet is among the most influential lifestyle factors impacting chronic disease risk. Nutrimetabolomics, the application of metabolomics to nutrition research, allows for the detection of food-specific compounds (FSCs) that can be used to connect dietary patterns, such as a Mediterranean-style (MED) diet, to health. This validation study is based upon analyses from a controlled feeding MED intervention, where our team identified FSCs from eight foods that can be detected in biospecimens after consumption and may therefore serve as food intake biomarkers.

Salmon Food-Specific Compounds and Their Metabolites Increase in Human Plasma and Are Associated with Cardiometabolic Health Indicators Following a Mediterranean-Style Diet Intervention.

Background: Nutrimetabolomics allows for the comprehensive analysis of foods and human biospecimens to identify biomarkers of intake and begin to probe their associations with health. Salmon contains hundreds of compounds that may provide cardiometabolic benefits.

Objectives: We used untargeted metabolomics to identify salmon food-specific compounds (FSCs) and their predicted metabolites that were found in plasma after a salmon-containing Mediterranean-style (MED) diet intervention.

Maternal nutritional status modifies heat-associated growth restriction in women with chronic malnutrition.

Rapid changes in the global climate are deepening existing health disparities from resource scarcity and malnutrition. Rising ambient temperatures represent an imminent risk to pregnant women and infants. Both maternal malnutrition and heat stress during pregnancy contribute to poor fetal growth, the leading cause of diminished child development in low-resource settings.

Longitudinal Reduction in Diversity of Maternal Gut Microbiota During Pregnancy Is Observed in Multiple Low-Resource Settings: Results From the Women First Trial.

Objective: To characterize the changes in gut microbiota during pregnancy and determine the effects of nutritional intervention on gut microbiota in women from sub-Saharan Africa (the Democratic Republic of the Congo, DRC), South Asia (India and Pakistan), and Central America (Guatemala).

Methods: Pregnant women in the Women First (WF) Preconception Maternal Nutrition Trial were included in this analysis. Participants were randomized to receive a lipid-based micronutrient supplement either ≥3 months before pregnancy (Arm 1); started the same intervention late in the first trimester (Arm 2); or received no nutrition supplements besides those self-administered or prescribed through local health services (Arm 3).

Opportunities and challenges for the use of common controls in sequencing studies.

Genome-wide association studies using large-scale genome and exome sequencing data have become increasingly valuable in identifying associations between genetic variants and disease, transforming basic research and translational medicine. However, this progress has not been equally shared across all people and conditions, in part due to limited resources. Leveraging publicly available sequencing data as external common controls, rather than sequencing new controls for every study, can better allocate resources by augmenting control sample sizes or providing controls where none existed.

Accessible analysis of longitudinal data with linear mixed effects models.

Longitudinal studies are commonly used to examine possible causal factors associated with human health and disease. However, the statistical models, such as two-way ANOVA, often applied in these studies do not appropriately model the experimental design, resulting in biased and imprecise results. Here, we describe the linear mixed effects (LME) model and how to use it for longitudinal studies.

RAREsim: A simulation method for very rare genetic variants.

Identification of rare-variant associations is crucial to full characterization of the genetic architecture of complex traits and diseases. Essential in this process is the evaluation of novel methods in simulated data that mirror the distribution of rare variants and haplotype structure in real data. Additionally, importing real-variant annotation enables in silico comparison of methods, such as rare-variant association tests and polygenic scoring methods, that focus on putative causal variants.

Effects of Complementary Feeding With Different Protein-Rich Foods on Infant Growth and Gut Health: Study Protocol.

An urgent need exists for evidence-based dietary guidance early in life, particularly regarding protein intake. However, a significant knowledge gap exists in the effects of protein-rich foods on growth and development during early complementary feeding. This is a randomized controlled trial of infant growth and gut health (primary outcomes).

Genome-wide analysis of copy number variants and normal facial variation in a large cohort of Bantu Africans.

Similarity in facial characteristics between relatives suggests a strong genetic component underlies facial variation. While there have been numerous studies of the genetics of facial abnormalities and, more recently, single nucleotide polymorphism (SNP) genome-wide association studies (GWASs) of normal facial variation, little is known about the role of genetic structural variation in determining facial shape. In a sample of Bantu African children, we found that only 9% of common copy number variants (CNVs) and 10-kb CNV analysis windows are well tagged by SNPs (r ≥ 0.

Summix: A method for detecting and adjusting for population structure in genetic summary data.

Publicly available genetic summary data have high utility in research and the clinic, including prioritizing putative causal variants, polygenic scoring, and leveraging common controls. However, summarizing individual-level data can mask population structure, resulting in confounding, reduced power, and incorrect prioritization of putative causal variants. This limits the utility of publicly available data, especially for understudied or admixed populations where additional research and resources are most needed.

Improved first trimester maternal iodine status with preconception supplementation: The Women First Trial.

Maternal iodine (I) status is critical in embryonic and foetal development. We examined the effect of preconception iodine supplementation on maternal iodine status and on birth outcomes. Non-pregnant women in Guatemala, India and Pakistan (n ~ 100 per arm per site) were randomized ≥ 3 months prior to conception to one of three intervention arms: a multimicronutrient-fortified lipid-based nutrient supplement containing 250-μg I per day started immediately after randomization (Arm 1), the same supplement started at ~12 weeks gestation (Arm 2) and no intervention supplement (Arm 3).

Genome-wide copy number variations in a large cohort of bantu African children.

Background: Copy number variations (CNVs) account for a substantial proportion of inter-individual genomic variation. However, a majority of genomic variation studies have focused on single-nucleotide variations (SNVs), with limited genome-wide analysis of CNVs in large cohorts, especially in populations that are under-represented in genetic studies including people of African descent.

Methods: We carried out a genome-wide copy number analysis in > 3400 healthy Bantu Africans from Tanzania.

Lipidomics-Based Comparison of Molecular Compositions of Green, Yellow, and Red Bell Peppers.

Identifying and annotating the molecular composition of individual foods will improve scientific understanding of how foods impact human health and how much variation exists in the molecular composition of foods of the same species. The complexity of this task includes distinct varieties and variations in natural occurring pigments of foods. Lipidomics, a sub-field of metabolomics, has emerged as an effective tool to help decipher the molecular composition of foods.

Different Blood Metabolomics Profiles in Infants Consuming a Meat- or Dairy-Based Complementary Diet.

Background: Research is limited in evaluating the mechanisms responsible for infant growth in response to different protein-rich foods; Methods: Targeted and untargeted metabolomics analysis were conducted on serum samples collected from an infant controlled-feeding trial that participants consumed a meat- vs. dairy-based complementary diet from 5 to 12 months of age, and followed up at 24 months.

Results: Isoleucine, valine, phenylalanine increased and threonine decreased over time among all participants; Although none of the individual essential amino acids had a significant impact on changes in growth Z scores from 5 to 12 months, principal component heavily weighted by BCAAs (leucine, isoleucine, valine) and phenylalanine had a positive association with changes in length-for-age Z score from 5 to 12 months.