Genome-wide association study reveals shared and distinct genetic architecture underlying fatty acid and bioactive oxylipin metabolites in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Bioactive fatty acid-derived oxylipin molecules play key roles in mediating inflammation and oxidative stress, which underlie many chronic diseases. Circulating levels of fatty acids and oxylipins are influenced by both environmental and genetic factors; characterizing the genetic architecture of bioactive lipids could yield new insights into underlying biological pathways. Thus, we performed a genome wide association study (GWAS) of n=81 fatty acids and oxylipins in n=11,584 Hispanic Community Health Study/Study of Latinos (HCHS/SOL) participants with genetic and lipidomic data measured at study baseline (58.6% female, mean age = 46.1 years, standard deviation = 13.8 years). Additionally, given the effects of central obesity on inflammation, we examined interactions with waist circumference using two-degree-of-freedom joint tests. Heritability estimates ranged from 0% to 47.9%, and 48 of the 81oxylipins and fatty acids were significantly heritable. Moreover, 40 (49.4%) of the 81 oxylipins and fatty acids had at least one genome-wide significant ( p < 6.94E-11) variant resulting in 19 independent genetic loci involved in fatty acid and oxylipin synthesis, as well as downstream pathways. Four loci (lead variant minor allele frequency [MAF] range: 0.08-0.50), including the desaturase-encoding FADS and the OATP1B1 transporter protein-encoding SLCO1B1 , exhibited associations with four or more fatty acids and oxylipins. The majority of the 15 remaining loci (87.5%) (lead variant MAF range = 0.03-0.45, mean = 0.23) were only associated with one oxylipin or fatty acid, demonstrating evidence of distinct genetic effects. Finally, while most loci identified in two-degree-of-freedom tests were previously identified in our main effects analyses, we also identified an additional rare variant (MAF = 0.002) near CARS2 , a locus previously implicated in inflammation. Our analyses revealed shared and distinct genetic architecture underlying fatty acids and oxylipins, providing insights into genetic factors and motivating future multi-omics work to characterize these compounds and elucidate their roles in disease pathways.

Erratum: Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits-The Hispanic/Latino Anthropometry Consortium.

[This corrects the article DOI: 10.1016/j.xhgg.2022.100099.].

The Role of State Mobilization for Volunteerism in China.

Research on China's volunteerism highlights the state as a major force in mobilizing volunteer participation. Nevertheless, limited quantitative research exists documenting the extent to which Chinese volunteers are connected to the state system. Using a nationally representative dataset, the 2012 Chinese General Social Survey, this study examines how an individual's employment affiliation with state-controlled institutions influences their probability to volunteer. The results show that the Chinese government not only directly mobilizes employees of the state system to volunteer but also has significant influence over the general population's volunteering. This influence is mainly through the existence of Chinese Communist Party chapters in every corner of society, as well as the state's direct and indirect control over social organizations that organize volunteer activities. We thus question the extent to which volunteerism in China is truly voluntary and call for more critical analysis of this issue.

Selecting scaling indicators in structural equation models (sems).

It is common practice for psychologists to specify models with latent variables to represent concepts that are difficult to directly measure. Each latent variable needs a scale, and the most popular method of scaling as well as the default in most structural equation modeling (SEM) software uses a scaling or reference indicator. Much of the time, the choice of which indicator to use for this purpose receives little attention, and many analysts use the first indicator without considering whether there are better choices. When all indicators of the latent variable have essentially the same properties, then the choice matters less. But when this is not true, we could benefit from scaling indicator guidelines. Our article first demonstrates why latent variables need a scale. We then propose a set of criteria and accompanying diagnostic tools that can assist researchers in making informed decisions about scaling indicators. The criteria for a good scaling indicator include high face validity, high correlation with the latent variable, factor complexity of one, no correlated errors, no direct effects with other indicators, a minimal number of significant overidentification equation tests and modification indices, and invariance across groups and time. We demonstrate these criteria and diagnostics using two empirical examples and provide guidance on navigating conflicting results among criteria. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Strengthening Causal Inference in Exposomics Research: Application of Genetic Data and Methods.

Advances in technologies to measure a broad set of exposures have led to a range of exposome research efforts. Yet, these efforts have insufficiently integrated methods that incorporate genetic data to strengthen causal inference, despite evidence that many exposome-associated phenotypes are heritable. Objective: We demonstrate how integration of methods and study designs that incorporate genetic data can strengthen causal inference in exposomics research by helping address six challenges: reverse causation and unmeasured confounding, comprehensive examination of phenotypic effects, low efficiency, replication, multilevel data integration, and characterization of tissue-specific effects. Examples are drawn from studies of biomarkers and health behaviors, exposure domains where the causal inference methods we describe are most often applied. Discussion: Technological, computational, and statistical advances in genotyping, imputation, and analysis, combined with broad data sharing and cross-study collaborations, offer multiple opportunities to strengthen causal inference in exposomics research. Full application of these opportunities will require an expanded understanding of genetic variants that predict exposome phenotypes as well as an appreciation that the utility of genetic variants for causal inference will vary by exposure and may depend on large sample sizes. However, several of these challenges can be addressed through international scientific collaborations that prioritize data sharing. Ultimately, we anticipate that efforts to better integrate methods that incorporate genetic data will extend the reach of exposomics research by helping address the challenges of comprehensively measuring the exposome and its health effects across studies, the life course, and in varied contexts and diverse populations. https://doi.org/10.1289/EHP9098.

Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits-The Hispanic/Latino Anthropometry Consortium.

Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (stage 1, n = 59,771) and generalized our findings in 9 additional studies (stage 2, n = 10,538). We conducted a trans-ancestral GWAS with summary statistics from HISLA stage 1 and existing consortia of European and African ancestries. In our HISLA stage 1 + 2 analyses, we discovered one BMI locus, as well as two BMI signals and another height signal each within established anthropometric loci. In our trans-ancestral meta-analysis, we discovered three BMI loci, one height locus, and one WHRadjBMI locus. We also identified 3 secondary signals for BMI, 28 for height, and 2 for WHRadjBMI in established loci. We show that 336 known BMI, 1,177 known height, and 143 known WHRadjBMI (combined) SNPs demonstrated suggestive transferability (nominal significance and effect estimate directional consistency) in Hispanic/Latino adults. Of these, 36 BMI, 124 height, and 11 WHRadjBMI SNPs were significant after trait-specific Bonferroni correction. Trans-ancestral meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our findings demonstrate that future studies may also benefit from leveraging diverse ancestries and differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification.

An introduction to model implied instrumental variables using two stage least squares (MIIV-2SLS) in structural equation models (SEMs).

Structural equation models (SEMs) are widely used to handle multiequation systems that involve latent variables, multiple indicators, and measurement error. Maximum likelihood (ML) and diagonally weighted least squares (DWLS) dominate the estimation of SEMs with continuous or categorical endogenous variables, respectively. When a model is correctly specified, ML and DWLS function well. But, in the face of incorrect structures or nonconvergence, their performance can seriously deteriorate. Model implied instrumental variable, two stage least squares (MIIV-2SLS) estimates and tests individual equations, is more robust to misspecifications, and is noniterative, thus avoiding nonconvergence. This article is an overview and tutorial on MIIV-2SLS. It reviews the six major steps in using MIIV-2SLS: (a) model specification; (b) model identification; (c) latent to observed (L2O) variable transformation; (d) finding MIIVs; (e) using 2SLS; and (f) tests of overidentified equations. Each step is illustrated using a running empirical example from Reisenzein's (1986) randomized experiment on helping behavior. We also explain and illustrate the analytic conditions under which an equation estimated with MIIV-2SLS is robust to structural misspecifications. We include additional sections on MIIV approaches using a covariance matrix and mean vector as data input, conducting multilevel SEM, analyzing categorical endogenous variables, causal inference, and extensions and applications. Online supplemental material illustrates input code for all examples and simulations using the R package MIIVsem. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Importance of Genetic Studies of Cardiometabolic Disease in Diverse Populations.

Genome-wide association studies have revolutionized our understanding of the genetic underpinnings of cardiometabolic disease. Yet, the inadequate representation of individuals of diverse ancestral backgrounds in these studies may undercut their ultimate potential for both public health and precision medicine. The goal of this review is to describe the imperativeness of studying the populations who are most affected by cardiometabolic disease, to the aim of better understanding the genetic underpinnings of the disease. We support this premise by describing the current variation in the global burden of cardiometabolic disease and emphasize the importance of building a globally and ancestrally representative genetics evidence base for the identification of population-specific variants, fine-mapping, and polygenic risk score estimation. We discuss the important ethical, legal, and social implications of increasing ancestral diversity in genetic studies of cardiometabolic disease and the challenges that arise from the (1) lack of diversity in current reference populations and available analytic samples and the (2) unequal generation of health-associated genomic data and their prediction accuracies. Despite these challenges, we conclude that additional, unprecedented opportunities lie ahead for public health genomics and the realization of precision medicine, provided that the gap in diversity can be systematically addressed. Achieving this goal will require concerted efforts by social, academic, professional and regulatory stakeholders and communities, and these efforts must be based on principles of equity and social justice.