scholarly journals Findings from the Hispanic Community Health Study/Study of Latinos on the Importance of Sociocultural Environmental Interactors: Polygenic Risk Score-by-Immigration and Dietary Interactions

2021 ◽  
Vol 12 ◽  
Author(s):  
Cristin E. McArdle ◽  
Hassan Bokhari ◽  
Clinton C. Rodell ◽  
Victoria Buchanan ◽  
Liana K. Preudhomme ◽  
...  
Keyword(s):  
Community Health ◽  
Genome Wide Association Study ◽  
The United States ◽  
European Ancestry ◽  
Risk Scores ◽  
Health Study ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Hispanic Community

Introduction: Hispanic/Latinos experience a disproportionate burden of obesity. Acculturation to US obesogenic diet and practices may lead to an exacerbation of innate genetic susceptibility. We examined the role of gene–environment interactions to better characterize the sociocultural environmental determinants and their genome-scale interactions, which may contribute to missing heritability of obesity. We utilized polygenic risk scores (PRSs) for body mass index (BMI) to perform analyses of PRS-by-acculturation and other environmental interactors among self-identified Hispanic/Latino adults from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).Methods: PRSs were derived using genome-wide association study (GWAS) weights from a publicly available, large meta-analysis of European ancestry samples. Generalized linear models were run using a set of a priori acculturation-related and environmental factors measured at visit 1 (2008–2011) and visit 2 (2014–2016) in an analytic subsample of 8,109 unrelated individuals with genotypic, phenotypic, and complete case data at both visits. We evaluated continuous measures of BMI and waist-to-hip ratio. All models were weighted for complex sampling design, combined, and sex-stratified.Results: Overall, we observed a consistent increase of BMI with greater PRS across both visits. We found the best-fitting model adjusted for top five principal components of ancestry, sex, age, study site, Hispanic/Latino background genetic ancestry group, sociocultural factors and PRS interactions with age at immigration, years since first arrival to the United States (p < 0.0104), and healthy diet (p < 0.0036) and explained 16% of the variation in BMI. For every 1-SD increase in PRS, there was a corresponding 1.10 kg/m2 increase in BMI (p < 0.001). When these results were stratified by sex, we observed that this 1-SD effect of PRS on BMI was greater for women than men (1.45 vs. 0.79 kg/m2, p < 0.001).Discussion: We observe that age at immigration and the adoption of certain dietary patterns may play a significant role in modifying the effect of genetic risk on obesity. Careful consideration of sociocultural and immigration-related factors should be evaluated. The role of nongenetic factors, including the social environment, should not be overlooked when describing the performance of PRS or for promoting population health in understudied populations in genomics.

scholarly journals Recent shifts in the genomic ancestry of Mexican Americans may alter the genetic architecture of biomedical traits

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Melissa L Spear ◽  
Alex Diaz-Papkovich ◽  
Elad Ziv ◽  
Joseph M Yracheta ◽  
Simon Gravel ◽  
...  
Keyword(s):  
Complex Traits ◽  
Mexican Americans ◽  
Genetic Architecture ◽  
Genome Wide Association Study ◽  
The United States ◽  
European Ancestry ◽  
Risk Scores ◽  
Health Study ◽  
Complex Interactions ◽  
Hispanic Community

People in the Americas represent a diverse continuum of populations with varying degrees of admixture among African, European, and Amerindigenous ancestries. In the United States, populations with non-European ancestry remain understudied, and thus little is known about the genetic architecture of phenotypic variation in these populations. Using genotype data from the Hispanic Community Health Study/Study of Latinos, we find that Amerindigenous ancestry increased by an average of ~20% spanning 1940s-1990s in Mexican Americans. These patterns result from complex interactions between several population and cultural factors which shaped patterns of genetic variation and influenced the genetic architecture of complex traits in Mexican Americans. We show for height how polygenic risk scores based on summary statistics from a European-based genome-wide association study perform poorly in Mexican Americans. Our findings reveal temporal changes in population structure within Hispanics/Latinos that may influence biomedical traits, demonstrating a need to improve our understanding of admixed populations.

scholarly journals Polygenic Risk Scores Augment Stroke Subtyping

2021 ◽  
Vol 7 (2) ◽  
pp. e560
Author(s):  
Jiang Li ◽  
Durgesh P. Chaudhary ◽  
Ayesha Khan ◽  
Christoph Griessenauer ◽  
David J. Carey ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Genetic Correlation ◽  
Genome Wide Association Study ◽  
Low Frequency ◽  
European Ancestry ◽  
Risk Scores ◽  
Polygenic Risk Score ◽  
Large Artery ◽  
Polygenic Risk ◽  
Gene Sets

ObjectiveTo determine whether the polygenic risk score (PRS) derived from MEGASTROKE is associated with ischemic stroke (IS) and its subtypes in an independent tertiary health care system and to identify the PRS derived from gene sets of known biological pathways associated with IS.MethodsControls (n = 19,806/7,484, age ≥69/79 years) and cases (n = 1,184/951 for discovery/replication) of acute IS with European ancestry and clinical risk factors were identified by leveraging the Geisinger Electronic Health Record and chart review confirmation. All Geisinger MyCode patients with age ≥69/79 years and without any stroke-related diagnostic codes were included as low risk control. Genetic heritability and genetic correlation between Geisinger and MEGASTROKE (EUR) were calculated using the summary statistics of the genome-wide association study by linkage disequilibrium score regression. All PRS for any stroke (AS), any ischemic stroke (AIS), large artery stroke (LAS), cardioembolic stroke (CES), and small vessel stroke (SVS) were constructed by PRSice-2.ResultsA moderate heritability (10%–20%) for Geisinger sample as well as the genetic correlation between MEGASTROKE and the Geisinger cohort was identified. Variation of all 5 PRS significantly explained some of the phenotypic variations of Geisinger IS, and the R2 increased by raising the cutoff for the age of controls. PRSLAS, PRSCES, and PRSSVS derived from low-frequency common variants provided the best fit for modeling (R2 = 0.015 for PRSLAS). Gene sets analyses highlighted the association of PRS with Gene Ontology terms (vascular endothelial growth factor, amyloid precursor protein, and atherosclerosis). The PRSLAS, PRSCES, and PRSSVS explained the most variance of the corresponding subtypes of Geisinger IS suggesting shared etiologies and corroborated Geisinger TOAST subtyping.ConclusionsWe provide the first evidence that PRSs derived from MEGASTROKE have value in identifying shared etiologies and determining stroke subtypes.

O-116 Genetic association analyses identify links between pelvic prolapse (PP) and connective tissue biology, cardiovascular and reproductive health

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
N Pujol Gualdo ◽  
K Läll ◽  
M Lepamets ◽  
R Arffman ◽  
T Piltonen ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Risk Scores ◽  
Polygenic Risk ◽  
Genome Wide ◽  
Meta Analyses ◽  
Personalized Risk

Abstract Study question Can genome-wide association analysis unravel the biological underpinnings of PP and facilitate personalized risk assessment via genetic risk scores construction? Summary answer We unravel novel links with urogenital development and vascular health in PP and present polygenic risk score as a tool to stratify PP risk. What is known already Prolapse is characterized by a descent of the pelvic organs into the vaginal cavity. PP affects around 40% of women after menopause and is the main indication for major gynecological surgery, having an important health, social and economic burden. Although the etiology and biological mechanisms underlying PP remain poorly understood, prior studies suggest genetic factors might play a role. Recently, a genome-wide association study (GWAS) identified seven genome-wide significant loci, located in or near genes involved in connective tissue metabolism and estrogen exposure in the etiology of PP. Study design, size, duration We conducted a three-stage case-control genome-wide association study. Firstly, in the discovery phase, we meta-analyzed Icelandic, UK Biobank and the FinnGen R3 datasets, comprising a total of 20118 cases and 427426 controls of European ancestry. For replication we used an independent dataset from Estonian Biobank (7968 cases and 118895 controls). Finally, we conducted a joint meta-analysis, containing 28086 cases and 546321 controls, which is the largest GWAS of PP to date. Participants/materials, setting, methods We performed functional annotation on genetic variants unraveled by GWAS and integrated these with expression quantitative trait loci and chromatin interaction data. In addition, we looked at enrichment of association signal on gene-set, tissue and cell type level and analyzed associations with other phenotypes both on genetic and phenotypic level. Colocalisation analyses were conducted to help pinpoint causal genes. We further constructed polygenic risk scores to explore options for personalized risk assessment and prevention. Main results and the role of chance In the discovery phase, we identified 18 genetic loci and 20 genetic variants significantly associated with POP (p < 5 × 10−8) and 75% of the variants show nominal significance association (p < 0.05) in the replication. Notably, the joint meta-analyses detected 20 genetic loci significantly associated with POP, from which 13 loci were novel. Novel genetic variants are located in or near genes involved in gestational duration and preterm birth (rs2687728 p = 2.19x10-9, EEFSEC), cardiovascular health and pregnancy success (rs1247943 p = 5.83x10-18, KLF13), endometriosis (rs12325192 p = 3.72x10-18, CRISPLD2), urogenital tract development (rs7126322, p = 4.35x10-15, WT1 and rs42400, p = 4.8x10-10, ADAMTS16) and regulation of the oxytocin receptor (rs2267372, p = 4.49x10-13, MAFF). Further analyses demonstrated that POP GWAS signals colocalise with several eQTLS (including EEFSEC, MAFF, KLF13, etc.), providing further evidence for mapping associated genes. Tissue and cell enrichment analyses underlined the role of the urogenital system, muscle cells, myocytes and adipocytes (p < 0.00001, FDR<0.05). Furthermore, genetic correlation analyses supported a shared genetic background with gastrointestinal disorders, joint and musculoskeletal disorders and cardiovascular disease. Polygenic risk scores analyses included a total of 125551 people in the target dataset, with 5379 prevalent patients and 2517 incident patients. Analyzing the best GRS as a quintile showed association with incident disease (Harrell c-statistic= 0.603, SD = 0.006). Limitations, reasons for caution This GWAS meta-analyses focused on European ancestry populations, which challenges the generalizability of GWAS findings to non-European populations. Moreover, this study included women with PP from population-based biobanks identified using the ICD-10 code N81, which limits analyses considering different disease stages and severity. Wider implications of the findings Our study provides genetic evidence to improve the current understanding of PP pathogenesis and serves as basis for further functional studies. Moreover, we provide a genetic tool for personalized risk stratification, which could help prevent PP development and improve the quality of a vast quantity of women. Trial registration number not applicable

scholarly journals Cognition and Daily Functioning: Results from the Hispanic Community Health Study/Study of Latinos (SOL) and Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA)

2020 ◽  
Vol 77 (3) ◽  
pp. 1267-1278
Author(s):  
Ariana M. Stickel ◽  
Wassim Tarraf ◽  
Benson Wu ◽  
Maria J. Marquine ◽  
Priscilla M. Vásquez ◽  
...  
Keyword(s):  
Community Health ◽  
Community Dwelling ◽  
Health Study ◽  
Cognitive Measures ◽  
Everyday Functioning ◽  
Older Adulthood ◽  
Hispanic Community ◽  
Ordered Logistic Regression ◽  
Neurocognitive Aging

Background: Among older adults, poorer cognitive functioning has been associated with impairments in instrumental activities of daily living (IADLs). However, IADL impairments among older Hispanics/Latinos is poorly understood. Objective: To characterize the relationships between cognition and risk for IADL impairment among diverse Hispanics/Latinos. Methods: Participants included 6,292 community-dwelling adults from the Study of Latinos - Investigation of Neurocognitive Aging, an ancillary study of 45+ year-olds in the Hispanic Community Health Study/Study of Latinos. Cognitive data (learning, memory, executive functioning, processing speed, and a Global cognitive composite) were collected at Visit 1. IADL functioning was self-reported 7 years later, and treated as a categorical (i.e., risk) and continuous (i.e., degree) measures of impairment. Survey two-part models (mixture of logit and generalized linear model with Gaussian distribution) and ordered logistic regression tested the associations of cognitive performance (individual tests and composite z-score) with IADL impairment. Additionally, we investigated the moderating role of age, sex, and Hispanic/Latino background on the association between cognition and IADL impairment. Results: Across all cognitive measures, poorer performance was associated with higher odds of IADL impairment 7 years later. Associations were generally stronger for the oldest group (70+ years) relative to the youngest group (50–59 years). Sex and Hispanic/Latino background did not modify the associations. Across the full sample, lower scores on learning, memory, and the Global cognitive composite were also associated with higher degree of IADL impairment. Conclusion: Across diverse Hispanics/Latinos, cognitive health is an important predictor of everyday functioning 7 years later, especially in older adulthood.

scholarly journals Empirically Derived Dietary Patterns Using Robust Profile Clustering in the Hispanic Community Health Study/Study of Latinos

2020 ◽  
Vol 150 (10) ◽  
pp. 2825-2834
Author(s):  
Briana J K Stephenson ◽  
Daniela Sotres-Alvarez ◽  
Anna-Maria Siega-Riz ◽  
Yasmin Mossavar-Rahmani ◽  
Martha L Daviglus ◽  
...  
Keyword(s):  
United States ◽  
Community Health ◽  
Dietary Patterns ◽  
Latent Class ◽  
The United States ◽  
Ethnic Background ◽  
Latent Class Models ◽  
Nutrition Intervention ◽  
Health Study ◽  
Hispanic Community

ABSTRACT Background Latent class models (LCMs) have been used in exploring dietary behaviors over a wide set of foods and beverages in a given population, but are prone to overgeneralize these habits in the presence of variation by subpopulations. Objectives This study aimed to highlight unique dietary consumption differences by both study site and ethnic background of Hispanic/Latino populations in the United States, that otherwise might be missed in a traditional LCM of the overall population. This was achieved using a new model-based clustering method, referred to as robust profile clustering (RPC). Methods A total of 11,320 individuals aged 18–74 y from the Hispanic Community Health Study/Study of Latinos (2008–2011) with complete diet data were classified into 9 subpopulations, defined by study site (Bronx, Chicago, Miami, San Diego) and ethnic background. At baseline, dietary intake was ascertained using a food propensity questionnaire. Dietary patterns were derived from 132 food groups using the RPC method to identify patterns of the general Hispanic/Latino population and those specific to an identified subpopulation. Dietary patterns derived from the RPC were compared to those identified from an LCM. Results The LCM identified 48 shared consumption behaviors of foods and beverages across the entire cohort, whereas significant consumption differences in subpopulations were identified in the RPC model for these same foods. Several foods were common within study site (e.g., chicken, orange juice, milk), ethnic background (e.g., papayas, plantain, coffee), or both (e.g., rice, tomatoes, seafood). Post hoc testing revealed an improved model fit in the RPC model [Deviance Information Criterion DICRPC = 2.3 × 104, DICLCM  = 9.5 × 106]. Conclusions Dietary pattern behaviors of Hispanics/Latinos in the United States tend to align by ethnic background for some foods and by location for other foods. Consideration of both factors is imperative to better understand their contributions to population health and developing targeted nutrition intervention studies.

scholarly journals Associations of Lipid Levels and Cognition: Findings from the Hispanic Community Health Study/Study of Latinos

2019 ◽  
Vol 26 (3) ◽  
pp. 251-262 ◽  
Author(s):  
Melissa Lamar ◽  
Ramon A. Durazo-Arvizu ◽  
Carlos J. Rodriguez ◽  
Robert C. Kaplan ◽  
Marisa J. Perera ◽  
...  
Keyword(s):  
Community Health ◽  
Verbal Fluency ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
The United States ◽  
Health Study ◽  
Linear Regression Models ◽  
Lipid Levels ◽  
Cholesterol Levels ◽  
Hispanic Community

AbstractObjective:Hispanics/Latinos in the United States are less aware of their cholesterol levels and have a higher burden of associated adverse cardiovascular and cerebrovascular outcomes than non-Latino whites. Investigations of the associations between cholesterol levels and cognition in this population have often occurred within the context of metabolic syndrome and are limited to select lipids despite the fact that triglycerides (TGs) may be more relevant to the health of Hispanics/Latinos.Methods:Baseline data from the Hispanic Community Health Study/Study of Latinos, collected from 2008 to 2011, was used to investigate the associations of lipid levels (i.e., TG, total cholesterol, TC; low-density and high-density lipoprotein cholesterol, LDL-C and HDL-C) with cognition (i.e., learning, memory, verbal fluency, and digit symbol substitution, DSS), adjusting for relevant confounders.Results:In 7413 participants ages 45 to 74 years from Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American backgrounds, separate, fully adjusted linear regression models revealed that TG levels were inversely associated with DSS performance; however, this relationship was no longer significant once additional cardiovascular disease risk factors were added to the model (p = .06). TC and LDL-C levels (separately) were positively associated with learning and verbal fluency regardless of adjustments (p-values < .05). Separate analyses investigating the effect modification by background and sex revealed a particularly robust association between TC levels and DSS performance for Puerto Ricans and Central Americans (albeit in opposite directions) and an inverse relationship between TG levels and DSS performance for women (p-values < .02).Conclusions:It is important to consider individual lipid levels and demographic characteristics when investigating associations between cholesterol levels and cognition in Hispanics/Latinos.

scholarly journals Inclusion of Variants Discovered from Diverse Populations Improves Polygenic Risk Score Transferability

2020 ◽  
Author(s):  
Taylor B. Cavazos ◽  
John S. Witte
Keyword(s):  
Genetic Risk ◽  
African Ancestry ◽  
European Ancestry ◽  
Risk Scores ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Genetic Risk Prediction ◽  
Causal Variants ◽  
The Uk ◽  
The Relationship

ABSTRACTThe majority of polygenic risk scores (PRS) have been developed and optimized in individuals of European ancestry and may have limited generalizability across other ancestral populations. Understanding aspects of PRS that contribute to this issue and determining solutions is complicated by disease-specific genetic architecture and limited knowledge of sharing of causal variants and effect sizes across populations. Motivated by these challenges, we undertook a simulation study to assess the relationship between ancestry and the potential bias in PRS developed in European ancestry populations. Our simulations show that the magnitude of this bias increases with increasing divergence from European ancestry, and this is attributed to population differences in linkage disequilibrium and allele frequencies of European discovered variants, likely as a result of genetic drift. Importantly, we find that including into the PRS variants discovered in African ancestry individuals has the potential to achieve unbiased estimates of genetic risk across global populations and admixed individuals. We confirm our simulation findings in an analysis of HbA1c, asthma, and prostate cancer in the UK Biobank. Given the demonstrated improvement in PRS prediction accuracy, recruiting larger diverse cohorts will be crucial—and potentially even necessary—for enabling accurate and equitable genetic risk prediction across populations.

scholarly journals Harnessing the power of polygenic risk scores to predict type 2 diabetes and its subtypes in a high-risk population of British Pakistanis and Bangladeshis in a routine healthcare setting

2021 ◽  
Author(s):  
Sam Hodgson ◽  
Qin Qin Huang ◽  
Neneh Sallah ◽  
Chris J Griffiths ◽  
William Newman ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
High Risk ◽  
European Ancestry ◽  
Risk Scores ◽  
P Value ◽  
High Risk Population ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
British Pakistanis

Background: Type 2 diabetes is a heterogeneous condition highly prevalent in British Pakistanis and Bangladeshis (BPB). The Genes & Health (G&H) cohort offers means to explore genetic determinants of disease in BPBs, combining genetic and lifelong health record data. Methods: We assessed whether common genetic loci associated with type 2 diabetes in European-ancestry individuals (EUR) replicate in G&H. We constructed a type 2 diabetes polygenic risk score (PRS) and combined it with a clinical risk instrument (QDiabetes) to build a novel, integrated risk tool (IRT). We compared IRT performance using net reclassification index (NRI) versus QDiabetes alone. We assessed the ability of the PRS to predict type 2 diabetes following gestational diabetes (GDM). We compared PRS distribution between type 2 diabetes subgroups identified by clinical features at diagnosis. Findings: Accounting for power, we replicated fewer loci associated with type 2 diabetes in G&H (n = 76/338, 22%) than would be expected if all EUR-ascertained loci were transferable (n = 95, 28%) (binomial p value = 0.01). In 13,648 patients free from type 2 diabetes followed up for 10 years, NRI was 3.2% for IRT versus QDiabetes (95% confidence interval 2.0 - 4.4%). IRT performance was best in reclassification of young adults deemed low risk by QDiabetes as high risk. PRS was independently associated with progression to type 2 diabetes after GDM (p = 0.028). Mean type 2 diabetes PRS differed between phenotypically-defined type 2 diabetes subgroups (p = 0.002). Interpretation: The type 2 diabetes PRS has broad potential clinical application in BPB, improving identification of type 2 diabetes risk (especially in the young), and characterisation of type 2 diabetes subgroups at diagnosis. Funding: Wellcome Trust, MRC, NIHR, and others. Full funding disclosed within.

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