Cardiometabolic traits vary considerably across ancestry groups, creating interest in disentangling the contributing factors to minimize health disparities. While environmental factors, such as ...socioeconomic status, access to healthcare, and lifestyle, are expected to play a large role in these differences, the contribution of genomics is less clear. This presentation will consider health disparities in cardiometabolic traits and the role of genomics can play in disentangling or exacerbating these disparities, with examples drawn from serum lipids and African ancestry populations. Serum lipids (especially HDL cholesterol and triglycerides) manifest clear differences in distribution across ancestries. While individuals of African ancestry often experience worse cardiometabolic outcomes (e.g., higher rates of hypertension, obesity, and diabetes), healthier mean serum lipid concentrations are generally observed among those of African ancestry. This lipid profile persists in those of West African ancestry across the African Diaspora, despite differences in social factors and lifestyle, lending support to genomic influences. This distribution, however, does not translate into a reduced rate of lipids‐associated cardiometabolic diseases, for reasons which are unclear, and this discrepancy has implications for use of lipid biomarkers for identifying individuals with disease risk. Well‐powered genomic studies of serum lipids in African ancestry individuals are emerging, revealing novel loci along with some evidence of gene‐lifestyle interactions and differing associations among subcontinental groups. These studies, along with increasing publications of other cardiometabolic traits in African and other non‐European ancestry individuals, are of great importance in a field plagued by underrepresentation of non‐European ancestry individuals. This underrepresentation has profound implications for the clinical utility of genomic discoveries. Without attention to this issue, genomics is poised to exacerbate health disparities in non‐EUR ancestry groups. African ancestry individuals are poorly represented in key genomic databases, yet their profound genetic diversity makes it likely to find variants among them that are not present in other populations. This imbalance can lead to clinical care that is sub‐optimal for those of African ancestry compared to better‐represented groups, a rising concern with increasing use of genomics in clinical decisions. For example, polygenic risk scores, derived from large, well‐powered GWAS, can predict disease risk for some traits of a magnitude that rivals Mendelian risk transmission, growing closer to clinical utility. Unfortunately, because of the comparatively limited representation of non‐European ancestry individuals in the underlying GWAS, these tools perform more poorly in these individuals. While these findings call for a greater number of genomic studies in diverse populations, attention also must be paid to the way individuals of non‐European ancestry are included and presented to ensure that the results facilitate the advancements their inclusion can address. Genomics has the potential to promote understanding of health disparities, but care must be given that they do not play a role in exacerbating them.
In post-World War II United States, a Holy Cross monk named Herman Zaccarelli viewed Vatican II as an opening for the modernising of food in Catholic religious institutions. Brother Herman founded ...the Food Research Center for Catholic Institutions on the campus of Stonehill College outside Boston, which ran conferences and seminars for monks and nuns who sought to change their approach to cooking and eating. Zaccarelli, a product of mid-twentieth century American cultural ideas and mores, grounded his efforts in religious obligation and located the change he sought within the "spirit of Vatican II". Many of the new ideas and practices ran counter to long-held habits and rituals regarding food - habits of restraint, asceticism and sacrifice, which set up intergenerational tensions. This story focuses on food to illustrate these larger tensions and transformations in post-WWII American Catholicism.
Conducting genomic research in diverse populations has led to numerous advances in our understanding of human history, biology, and health disparities, in addition to discoveries of vital clinical ...significance. Conducting genomic research in diverse populations is also important in ensuring that the genomic revolution does not exacerbate health disparities by facilitating discoveries that will disproportionately benefit well-represented populations. Despite the general agreement on the need for genomic research in diverse populations in terms of equity and scientific progress, genomic research remains largely focused on populations of European descent. In this article, we describe the rationale for conducting genomic research in diverse populations by reviewing examples of advances facilitated by their inclusion. We also explore some of the factors that perpetuate the disproportionate attention on well-represented populations. Finally, we discuss ongoing efforts to ameliorate this continuing bias. Collaborative and intensive efforts at all levels of research, from the funding of studies to the publication of their findings, will be necessary to ensure that genomic research does not conserve historical inequalities or curtail the contribution that genomics could make to the health of
all
humanity.
Impaired glucose tolerance is a major risk factor for type 2 diabetes (T2D) and several cardiometabolic disorders. To identify genetic loci underlying fasting glucose levels, we conducted an analysis ...of 9,232 individuals of European ancestry who at enrollment were either nondiabetic or had untreated type 2 diabetes. Multivariable linear mixed models were used to test for associations between fasting glucose and 7.9 million SNPs, with adjustment for age, body mass index (BMI), sex, significant principal components of the genotypes, and cryptic relatedness. Three previously discovered loci were genome-wide significant, with the lead SNPs being rs1260326, a missense variant in GCKR (p = 1.06×10-8); rs560887, an intronic variant in G6PC2 (p = 3.39×10-11); and rs13266634, a missense variant in SLC30A8 (p = 4.28×10-10). Fine mapping, genome-wide conditional analysis, and functional annotation indicated that the three loci were independently associated with fasting glucose. Each copy of an alternate allele at any of these three SNPs was associated with a reduction of 0.012 mmol/L in fasting glucose levels (p = 8.0×10-28), and this association was replicated in trans-ethnic analysis of 14,303 individuals (p = 2.2×10-16). The three SNPs were jointly associated with significantly reduced T2D risk, with an odds ratio (95% CI) of 0.93 (0.88, 0.98) per protective allele. Our findings implicate additive effects across pathophysiological pathways involved in type 2 diabetes, including glycolysis, gluconeogenesis, and insulin secretion. Since none of the individuals homozygous for the alternate alleles at all three loci has T2D, it might be possible to use a genetic predictor of fasting glucose levels to identify individuals at low vs. high risk of developing type 2 diabetes.
A deeper appreciation of the complex architecture of African genomes is critical to the global effort to understand human history, biology and differential distribution of disease by geography and ...ancestry. Here, we report on how the growing engagement of African populations in genome science is providing new insights into the forces that shaped human genomes before and after the Out-of-Africa migrations. As a result of this human evolutionary history, African ancestry populations have the greatest genomic diversity in the world, and this diversity has important ramifications for genomic research. In the case of pharmacogenomics, for instance, variants of consequence are not limited to those identified in other populations, and diversity within African ancestry populations precludes summarizing risk across different African ethnic groups. Exposure of Africans to fatal pathogens, such as Plasmodium falciparum, Lassa Virus and Trypanosoma brucei rhodesiense, has resulted in elevated frequencies of alleles conferring survival advantages for infectious diseases, but that are maladaptive in modern-day environments. Illustrating with cardiometabolic traits, we show that while genomic research in African ancestry populations is still in early stages, there are already many examples of novel and African ancestry-specific disease loci that have been discovered. Furthermore, the shorter haplotypes in African genomes have facilitated fine-mapping of loci discovered in other human ancestry populations. Given the insights already gained from the interrogation of African genomes, it is imperative to continue and increase our efforts to describe genomic risk in and across African ancestry populations.
Food consumption is a significant and complex social activity—and what a society chooses to feed its children reveals much about its tastes and ideas regarding health. In this groundbreaking ...historical work, Amy Bentley explores how the invention of commercial baby food shaped American notions of infancy and influenced the evolution of parental and pediatric care. Until the late nineteenth century, infants were almost exclusively fed breast milk. But over the course of a few short decades, Americans began feeding their babies formula and solid foods, frequently as early as a few weeks after birth. By the 1950s, commercial baby food had become emblematic of all things modern in postwar America. Little jars of baby food were thought to resolve a multitude of problems in the domestic sphere: they reduced parental anxieties about nutrition and health; they made caretakers feel empowered; and they offered women entering the workforce an irresistible convenience. But these baby food products laden with sugar, salt, and starch also became a gateway to the industrialized diet that blossomed during this period. Today, baby food continues to be shaped by medical, commercial, and parenting trends. Baby food producers now contend with health and nutrition problems as well as the rise of alternative food movements. All of this matters because, as the author suggests, it's during infancy that American palates become acclimated to tastes and textures, including those of highly processed, minimally nutritious, and calorie-dense industrial food products.
The lack of representation of diverse ancestral backgrounds in genomic research is well-known, and the resultant scientific and ethical limitations are becoming increasingly appreciated. The paucity ...of data on individuals with African ancestry is especially noteworthy as Africa is the birthplace of modern humans and harbors the greatest genetic diversity. It is expected that greater representation of those with African ancestry in genomic research will bring novel insights into human biology, and lead to improvements in clinical care and improved understanding of health disparities. Now that major efforts have been undertaken to address this failing, is there evidence of these anticipated advances? Here, we evaluate the promise of including diverse individuals in genomic research in the context of recent literature on individuals of African ancestry. In addition, we discuss progress and achievements on related technological challenges and diversity among scientists conducting genomic research.
Non-communicable diseases, including cardiovascular diseases (CVDs), are increasing in African populations. High serum low density lipoprotein cholesterol (LDL-cholesterol) levels are a known risk ...factor for CVDs in European populations, but the link remains poorly understood among Africans. This study investigated the associations between serum LDL-cholesterol levels and selected variants in the low density lipoprotein receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9) and low density lipoprotein receptor adaptor protein 1 (LDLRAP1) genes in some selected African populations. Nineteen SNPs were selected from publicly available African whole genome sequence data based on functional prediction and allele frequency. SNPs were genotyped in 1000 participants from the AWI-Gen, study selected from the extremes of LDL-cholesterol level distribution (500 with LDL-cholesterol>3.5 mmol/L and 500 with LDL-cholesterol<1.1 mmol/L). The minor alleles at five of the six associated SNPs were significantly associated (P<0.05) with lower LDL-cholesterol levels: LDLRAP1 rs12071264 (OR 0.56, 95% CI: 0.39-0.75, P = 2.73x10-4) and rs35910270 (OR 0.78, 95% CI: 0.64-0.94, P = 0.008); APOB rs6752026 (OR 0. 55, 95% CI: 0.41-0.72, P = 2.82x10-5); LDLR: rs72568855 (OR 0.47, 95% CI: 0.27-0.82, P = 0.008); and PCSK9 rs45613943 (OR = 0.72, 95% CI: 0.58-0.88, P = 0.001). The minor allele of the sixth variant was associated with higher LDL-cholesterol levels: APOB rs679899 (OR 1.41, 95% CI: 1.06-1.86, P = 0.016). A replication analysis in the Africa America Diabetes Mellitus (AADM) study found the PCSK9 variant to be significantly associated with low LDL-cholesterol levels (Beta = -0.10). Since Africans generally have lower LDL-cholesterol levels, these LDL-cholesterol associated variants may be involved in adaptation due to unique gene-environment interactions. In conclusion, using a limited number of potentially functional variants in four genes, we identified significant associations with lower LDL-cholesterol levels in sub-Saharan Africans.
European-ancestry populations are recognized as stratified but not as admixed, implying that residual confounding by locus-specific ancestry can affect studies of association, polygenic adaptation, ...and polygenic risk scores. We integrate individual-level genome-wide data from ~19,000 European-ancestry individuals across 79 European populations and five European American cohorts. We generate a new reference panel that captures ancestral diversity missed by both the 1000 Genomes and Human Genome Diversity Projects. Both Europeans and European Americans are admixed at the subcontinental level, with admixture dates differing among subgroups of European Americans. After adjustment for both genome-wide and locus-specific ancestry, associations between a highly differentiated variant in LCT (rs4988235) and height or LDL-cholesterol were confirmed to be false positives whereas the association between LCT and body mass index was genuine. We provide formal evidence of subcontinental admixture in individuals with European ancestry, which, if not properly accounted for, can produce spurious results in genetic epidemiology studies.
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