Genetic Diversity and Association Studies in US Hispanic/Latino Populations: Applications in the Hispanic Community Health Study/Study of Latinos

US Hispanic/Latino individuals are diverse in genetic ancestry, culture, and environmental exposures. Here, we characterized and controlled for this diversity in genome-wide association studies (GWASs) for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We simultaneously estimated population-structure principal components (PCs) robust to familial relatedness and pairwise kinship coefficients (KCs) robust to population structure, admixture, and Hardy-Weinberg departures. The PCs revealed substantial genetic differentiation within and among six self-identified background groups (Cuban, Dominican, Puerto Rican, Mexican, and Central and South American). To control for variation among groups, we developed a multi-dimensional clustering method to define a “genetic-analysis group” variable that retains many properties of self-identified background while achieving substantially greater genetic homogeneity within groups and including participants with non-specific self-identification. In GWASs of 22 biomedical traits, we used a linear mixed model (LMM) including pairwise empirical KCs to account for familial relatedness, PCs for ancestry, and genetic-analysis groups for additional group-associated effects. Including the genetic-analysis group as a covariate accounted for significant trait variation in 8 of 22 traits, even after we fit 20 PCs. Additionally, genetic-analysis groups had significant heterogeneity of residual variance for 20 of 22 traits, and modeling this heteroscedasticity within the LMM reduced genomic inflation for 19 traits. Furthermore, fitting an LMM that utilized a genetic-analysis group rather than a self-identified background group achieved higher power to detect previously reported associations. We expect that the methods applied here will be useful in other studies with multiple ethnic groups, admixture, and relatedness.     

Occupational Physical Activity and Body Mass Index: Results from the Hispanic Community Health Study / Study of Latinos

Purpose

To examine the associations between overweight/obesity and occupation among Hispanics/Latinos, the largest minority population in the U.S.

Methods

This study included 7,409 employed individuals in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a prospective study of Hispanic/Latino individuals aged 18–74 in four communities in the U.S. We independently examined the relationships between BMI, Occupational Activity (OA), and Total Hours Worked, quantified via self-reported hours worked per week and occupation-assigned Metabolic Equivalents (METs).

Results

More than three quarters of the participants were either overweight (39.3%) or obese (37.8%). Individuals with a primary occupation and those employed in a secondary occupation worked an average of 36.8 and 14.6 hrs/wk, respectively. The overall adjusted odds for being obese compared to normal weight were 3.2% (AOR = 1.03, 95% CI 1.01, 1.05) and 14.4% (AOR = 1.14 95% Cl 1.07, 1.23) greater for each 10 MET•hrs/wk unit of increased OA, and each 10-hrs/wk unit of Total Hours Worked, respectively.

Conclusion

This study presents the first findings on the association between OA with overweight/obesity among Hispanic/Latino individuals in the U.S. Increasing OA and Total Hours Worked per week were independently associated with increasing odds of overweight/obesity suggesting that the workplace is only one part of the overall energy expenditure dynamic. Our findings point to the need to emphasize engaging employed individuals in greater levels of PA outside of the work environment to impact overweight/obesity.     

Self-Reported Cancer Prevalence among Hispanics in the US: Results from the Hispanic Community Health Study/Study of Latinos

Cancer has surpassed heart disease as the leading cause of death among Hispanics in the U.S., yet data on cancer prevalence and risk factors in Hispanics in regard to ancestry remain scarce. This study sought to describe (a) the prevalence of cancer among Hispanics from four major U.S. metropolitan areas, (b) cancer prevalence across Hispanic ancestry, and (c) identify correlates of self-reported cancer prevalence. Participants were 16,415 individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), who self-identified as Cuban, Dominican, Mexican, Puerto Rican, Central or South American. All data were collected at a single time point during the HCHS/SOL baseline clinic visit. The overall self-reported prevalence rate of cancer for the population was 4%. The rates varied by Hispanic ancestry group, with individuals of Cuban and Puerto Rican ancestry reporting the highest cancer prevalence. For the entire population, older age (OR = 1.47, p < .001, 95% CI, 1.26–1.71) and having health insurance (OR = 1.93, p < .001, 95% CI, 1.42–2.62) were all significantly associated with greater prevalence, whereas male sex was associated with lower prevalence (OR = 0.56, p < .01, 95% CI, .40-.79). Associations between study covariates and cancer prevalence also varied by Hispanic ancestry. Findings underscore the importance of sociodemographic factors and health insurance in relation to cancer prevalence for Hispanics and highlight variations in cancer prevalence across Hispanic ancestry groups. Characterizing differences in cancer prevalence rates and their correlates is critical to the development and implementation of effective prevention strategies across distinct Hispanic ancestry groups.     

Cancer fatalism and adherence to national cancer screening guidelines: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

BackgroundSociocultural factors, such as health insurance status, income, education, and acculturation, predict cancer screening among U.S. Hispanics/Latinos. However, these factors can be difficult to modify. More research is needed to identify individual-level modifiable factors that may improve screening and subsequent cancer outcomes in this population. The aim of this study was to examine cancer fatalism (i.e., the belief that there is little or nothing one can do to lower his/her risk of developing cancer) as a determinant of adherence to national screening guidelines for colorectal, breast, prostate, and cervical cancer among Hispanics/Latinos.MethodsParticipants were from the multi-site Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Sociocultural Ancillary Study (N = 5313). The National Cancer Institute (NCI) Health Interview National Trends Survey was used to assess cancer fatalism and receipt of cancer screening. Adherence was defined as following screening guidelines from United States Preventive Services Task Force and the American Cancer Society during the study period.ResultsAdjusting for well-established determinants of cancer screening and covariates (health insurance status, income, education, acculturation, age, Hispanic/Latino background), lower cancer fatalism was marginally associated with greater adherence to screening for colorectal (OR 1.13, 95% CI [.99–1.30], p = .07), breast (OR 1.16, 95% CI [.99–1.36], p = .08) and prostate cancer (OR 1.18, 95% CI [.97–1.43], p = .10), but not cervical cancer.ConclusionsThe associations of cancer fatalism were small and marginal, underlining that sociocultural factors are more robust determinants of cancer screening adherence among Hispanics/Latinos.     

A genomewide admixture mapping panel for Hispanic/Latino populations

Admixture mapping (AM) is a promising method for the identification of genetic risk factors for complex traits and diseases showing prevalence differences among populations. Efficient application of this method requires the use of a genomewide panel of ancestry-informative markers (AIMs) to infer the population of origin of chromosomal regions in admixed individuals. Genomewide AM panels with markers showing high frequency differences between West African and European populations are already available for disease-gene discovery in African Americans. However, no such a map is yet available for Hispanic/Latino populations, which are the result of two-way admixture between Native American and European populations or of three-way admixture of Native American, European, and West African populations. Here, we report a genomewide AM panel with 2,120 AIMs showing high frequency differences between Native American and European populations. The average intermarker genetic distance is ~1.7 cM. The panel was identified by genotyping, with the Affymetrix GeneChip Human Mapping 500K array, a population sample with European ancestry, a Mesoamerican sample comprising Maya and Nahua from Mexico, and a South American sample comprising Aymara/Quechua from Bolivia and Quechua from Peru. The main criteria for marker selection were both high information content for Native American/European ancestry (measured as the standardized variance of the allele frequencies, also known as "f value") and small frequency differences between the Mesoamerican and South American samples. This genomewide AM panel will make it possible to apply AM approaches in many admixed populations throughout the Americas.     

Identifying Probable Diabetes Mellitus Among Hispanics/Latinos from Four U.S. Cities: Findings from the Hispanic Community Health Study/Study of Latinos

Objective: The aim of this study was to compare the ability of American Diabetes Association (ADA) diagnostic criteria to identify U.S. Hispanics/Latinos from diverse heritage groups with probable diabetes mellitus and assess cardiovascular risk factor correlates of those criteria.Methods: Cross-sectional analysis of data from 15,507 adults from 6 Hispanic/Latino heritage groups, enrolled in the Hispanic Community Health Study/Study of Latinos. The prevalence of probable diabetes mellitus was estimated using individual or combinations of ADA-defined cut points. The sensitivity and specificity of these criteria at identifying diabetes mellitus from ADA-defined prediabetes and normoglycemia were evaluated. Prevalence ratios of hypertension, abnormal lipids, and elevated urinary albumin-creatinine ratio for unrecognized diabetes mellitus—versus prediabetes and normoglycemia—were calculated.Results: Among Hispanics/Latinos (mean age, 43 years) with diabetes mellitus, 39.4% met laboratory test criteria for probable diabetes, and the prevalence varied by heritage group. Using the oral glucose tolerance test as the gold standard, the sensitivity of fasting plasma glucose (FPG) and hemoglobin A1c—alone or in combination—was low (18, 23, and 33%, respectively) at identifying probable diabetes mellitus. Individuals who met any criterion for probable diabetes mellitus had significantly higher (P<.05) prevalence of most cardiovascular risk factors than those with normoglycemia or prediabetes, and this association was not modified by Hispanic/Latino heritage group.Conclusion: FPG and hemoglobin A1c are not sensitive (but are highly specific) at detecting probable diabetes mellitus among Hispanics/Latinos, independent of heritage group. Assessing cardiovascular risk factors at diagnosis might prompt multitarget interventions and reduce health complications in this young population.Abbreviations:2hPG = 2-hour post–glucose load plasma glucoseADA = American Diabetes AssociationBMI = body mass indexCV = cardiovascularFPG = fasting plasma glucoseHbA1c = hemoglobin A1cHCHS/SOL = Hispanic Community Health Study/Study of LatinosHDL-C = high-density-lipoprotein cholesterolNGT = normal glucose toleranceNHANES = National Health and Nutrition Examination SurveyOGTT = oral glucose tolerance testTG = triglycerideUACR = urine albumin-creatinine ratio     

Sex-Specific Associations of Iron-Anemia Status With Hemoglobin A1C Levels Among Hispanics/Latinos Without Self-Reported Diabetes Mellitus: The Hispanic Community Health Study/Study of Latinos

ObjectiveThe objective of this study was to examine the sex-specific associations of mutually exclusive iron-anemia status categories with hemoglobin A1C (HbA1C) levels among U.S. Hispanics/Latinos without self-reported diabetes mellitus.MethodsBaseline cross-sectional data (7247 women and 4904 men without self-reported diabetes mellitus) from the Hispanic Community Health Study/Study of Latinos were analyzed. Per the American Diabetes Association’s defined criteria, based on HbA1C levels, the participants were categorized as having normoglycemia, prediabetes, or probable diabetes mellitus. The iron-anemia status categories were as follows: no anemia and no iron deficiency (reference), iron deficiency, iron deficiency anemia (IDA), and non-iron deficiency anemia (non-IDA). Survey multinomial logistic regression models were used to examine the sex-specific associations of iron-anemia status with HbA1C levels after adjusting for sociodemographic, lifestyle, and clinical factors.ResultsThe age-standardized prevalence of iron-anemia status categories differed by sex. Compared with those with no anemia and no iron deficiency and normoglycemia, women with IDA had higher odds of having prediabetes (odds ratio [OR], 2.18; 95% CI, 1.64-2.89) and probable diabetes mellitus (OR, 3.59; 95% CI, 1.62-7.99) based on HbA1C levels; men with non-IDA had higher odds of having probable diabetes mellitus (OR, 2.97; 95% CI, 1.13-7.78) based on HbA1C levels. All other associations did not reach statistical significance.ConclusionAmong U.S. Hispanics/Latinos without self-reported diabetes mellitus, the age-standardized prevalence of iron deficiency, IDA, and non-IDA is high and varies by sex. Women with IDA had higher odds of having prediabetes and probable diabetes mellitus, defined based on HbA1C levels. Men with non-IDA had higher odds of having probable diabetes mellitus, defined based on HbA1C levels. Iron-anemia status should be considered while interpreting elevated HbA1C levels among U.S. Hispanics/Latinos without self-reported diabetes mellitus.     

Genetic analysis of adiponectin and obesity in Hispanic families: the IRAS Family Study

Adiponectin, coded for by the APM1 gene, is a novel adipocyte-derived hormone implicated in energy homeostasis and obesity. Several genetic studies have observed evidence of association between APM1 gene polymorphisms and features of the metabolic syndrome, such as insulin resistance and obesity. As part of a comprehensive genetic analysis of the APM1 gene, we have screened 96 unrelated individuals for polymorphisms in the promoter, coding regions, and 3untranslated region (UTR). Three promoter single-nucleotide polymorphisms (SNPs), two rare coding SNPs (G113A and T1233C), and 13 SNPs in the 3UTR were identified. Eighteen SNPs were genotyped in 811 Hispanic individuals from 45 families in the IRAS Family Study (IRASFS). SNPs were tested for association with six obesity quantitative traits (body mass index, waist, waist:hip ratio, subcutaneous adipose tissue, visceral adipose tissue, and visceral:subcutaneous ratio). Significant evidence of association to at least one of the obesity traits was identified in seven of the 18 SNPs (<0.001–0.05). The promoter SNP INS CA-11156 was the most consistently associated SNP and was associated significantly with all measures of obesity, except the visceral:subcutaneous ratio (P-values 0.009–0.03). Haplotype analysis supported this evidence of association, with haplotypes containing an insertion of one CA repeat at position –11156 consistently being associated with lower obesity values (P-value <0.001–0.05). The adiponectin polymorphisms, in particular those in the promoter region, thus show significant association with obesity measures in the Hispanic population. Additional studies are needed to confirm our findings and determine which polymorphism causes the functional effect.     

Hispanic and Asian pubertal girls have higher android/gynoid fat ratio than whites

Objective: To examine differences in body size, composition, and distribution of body fat among Hispanic, white, and Asian adolescents. Research Methods and Procedures: This included cross‐sectional data from the baseline sample of the Adequate Calcium Today trial. Participants included 180 Asian, 234 Hispanic, and 325 white girls 11.8 ± 0.05 years of age from Arizona, California, Hawaii, Indiana, Ohio, and Nevada. Anthropometric and DXA measurements (Lunar Prodigy) were standardized across sites. Tanner pubertal stage was self‐selected from line drawings. Physical activity was assessed by a validated questionnaire. Comparisons between ethnic groups were examined using contrasts in the context of a general linear model. Results: Controlling for pubertal stage and study site only, Asians weighed less than Hispanics and were shorter than Hispanics and whites. Controlling for pubertal stage, height, weight, and study site, Asians had shorter leg lengths, smaller waist circumference, longer trunk lengths, more lean mass, less total fat mass, and less gynoid fat mass than Hispanics and whites; Asians had larger bitrochanteric width than whites; Asians had smaller DXA‐derived android fat mass than Hispanics; and whites had smaller mean android/gynoid fat ratio than Hispanics. However, whites had a smaller android/gynoid fat ratio than both Asians and Hispanics in a model that adjusted for ethnicity, pubertal stage, bitrochanteric width, waist circumference, trunk length, log of physical activity, and study site, which explained 77% of the variation. Discussion: Ethnic differences in fat distribution are partially explained by differences in skeletal dimensions.     

HLA-A/B haplotye frequencies among U.S. Hispanic and African-American populations

HLA-A/B haplotype frequency tables were developed for U.S. Hispanic and African-American populations from data collected from paternity cases. Two Hispanic tables were developed; one was based on data from Hispanics in the northeast U.S. and Florida and designated the Caribbean table whilte all other Hispanics were included in a table designated the Mexican table. The total number of individuals whose haplotypes were included in the Caribbean, Mexican, African-American tables was 1635, 2230, and 3134, respectively. Statistical comparisons were made of haplotype frequencies among these tables and tables previously reported.     

Results of a Free Spay/Neuter Program in a Hispanic Colonia on the Texas-Mexico Border

The purpose of this study, conducted in a small, impoverished Hispanic community on the Texas-Mexico border, was to evaluate the level of participation in a bilingual spay/neuter program offered free of charge to residents with companion animals. Prior to the sterilization project, approximately 11% of dogs and about 27% of cats with guardians underwent surgical sterilization. Over an 8-month period, the spay/neuter program sterilized about 47% of dogs and 38% of cats who had guardians in the community. In spite of residents' early reluctance to neuter their dogs, the project sterilized nearly equal numbers of male and female dogs (200 male; 201 female).     

Results of a free spay/neuter program in a Hispanic colonia on the Texas-Mexico border

The purpose of this study, conducted in a small, impoverished Hispanic community on the Texas-Mexico border, was to evaluate the level of participation in a bilingual spay/neuter program offered free of charge to residents with companion animals. Prior to the sterilization project, approximately 11% of dogs and about 27% of cats with guardians underwent surgical sterilization. Over an 8-month period, the spay/neuter program sterilized about 47% of dogs and 38% of cats who had guardians in the community. In spite of residents' early reluctance to neuter their dogs, the project sterilized nearly equal numbers of male and female dogs (200 male; 201 female).     

Genetic Analysis of Hispanic Individuals with Cystic Fibrosis

We have performed molecular genetic analyses of Hispanic individuals with cystic fibrosis (CF) in the southwestern United States. Of 129 CF chromosomes analyzed, only 46% (59/129) carry ΔF508. The G542X mutation was found on 5% (7/129) of CF chromosomes. The 3849+10kbC→T mutation, detected primarily in Ashkenazi Jews, was present on 2% (3/129). R1162X and R334W, mutations identified in Spain and Italy, each occurred on 1.6% (2/129) of CF chromosomes. W1282X and R553X were each detected once. G551D and N1303K were not found. Overall, screening for 22 or more mutations resulted in detection of only 58% of CF transmembrane conductance regulator gene mutations among Hispanic individuals. Analysis of KM19/XV2c haplotypes revealed an unusual distribution. Although the majority of ΔF508 mutations are on chromosomes of B haplotypes, the other CF mutations are on A and C haplotypes at higher-than-expected frequencies. These genetic analyses demonstrate significant differences between Hispanic individuals with CF and those of the general North American population. Assessment of carrier/affected risk in Hispanic CF individuals cannot, therefore, be based on the mutation frequencies found through studies of the general population but must be adjusted to better reflect the genetic makeup of this ethnic group. Further studies are necessary to identify the causative mutation(s) in this population and to better delineate genotype/phenotype correlations. These will enable counselors to provide more accurate genetic counseling.     

Symptoms of schizophrenia in Hispanic and Anglo veterans

This study explores cultural influences on symptoms and course of schizophrenic disorder. Hispanic veterans with schizophrenia are compared to a similar group of White non-Hispanic (Anglo) veterans. Symptoms were elicited with a structured diagnostic interview and a battery of rating instruments. Primary symptoms of schizophrenia (e.g., hallucinations, delusions, functional deterioration) were very similar for both groups. However, Hispanic patients reported a later age of onset, exhibited more somatization, and spent less time in the hospital than Anglo patients.This study was supported by a grant from the Veterans Administration Health Services Research and Development Service (Project 11R 81-633).     

Acculturation and Plasma Fatty Acid Concentrations in Hispanic and Chinese-American Adults: The Multi-Ethnic Study of Atherosclerosis

Background

Acculturation to the U.S. is associated with increased risk of cardiovascular disease, but the etiologic pathways are not fully understood. Plasma fatty acid levels exhibit ethnic differences and are emerging as biomarkers and predictors of cardiovascular disease risk. Thus, plasma fatty acids may represent one pathway underlying the association between acculturation and cardiovascular disease. We investigated the cross-sectional relationship between acculturation and plasma phospholipid fatty acids in a diverse sample of Hispanic- and Chinese-American adults.

Methods and Findings

Participants included 377 Mexican, 320 non-Mexican Hispanic, and 712 Chinese adults from the Multi-Ethnic Study of Atherosclerosis, who had full plasma phospholipid assays and acculturation information. Acculturation was determined from three proxy measures: nativity, language spoken at home, and years in the U.S., with possible scores ranging from 0 (least acculturated) to 5 (most acculturated) points. α-Linolenic acid, linoleic acid, eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid were measured in fasting plasma. Linear regression models were conducted in race/ethnicity-stratified analyses, with acculturation as the predictor and plasma phospholipid fatty acids as the outcome variables. We ran secondary analyses to examine associations between acculturation and dietary fatty acids for comparison. Covariates included age, gender, education, and income. Contrary to our hypothesis, no statistically significant associations were detected between acculturation and plasma phospholipid fatty acids for Chinese, non-Mexican Hispanic, or Mexican participants. However, acculturation was related to dietary total n-6 fatty acids and dietary n-3/n-6 ratios in expected directions for Mexican, non-Mexican Hispanic, and combined Hispanic participants. In Chinese individuals, acculturation was unexpectedly associated with lower arachidonic acid intake.

Conclusion

Absence of associations between acculturation and plasma phospholipid fatty acids suggests that changes in the plasma phospholipid fatty acids studied do not account for the observed associations of acculturation to the U.S. and cardiovascular disease risk. Similar findings were observed for eicosapentaenoic acid and docosahexaenoic acid, when using dietary intake. However, the observed associations between dietary n-6 fatty acids and acculturation in Hispanic individuals suggest that dietary intake may be more informative than phospholipids when investigating acculturation effects. In Chinese individuals, acculturation may have a possible protective effect through decreased arachidonic acid intake. Further research on dietary fatty acids and other cardiovascular disease biomarkers is needed to identify possible etiologic mechanisms between acculturation and cardiovascular disease.     

Genome‐wide Association Study and Follow‐up Analysis of Adiposity Traits in Hispanic Americans: The IRAS Family Study

We investigated candidate genomic regions associated with computed tomography (CT)–derived measures of adiposity in Hispanics from the Insulin Resistance Atherosclerosis Study Family Study (IRASFS). In 1,190 Hispanic individuals from 92 families 3 from the San Luis Valley, Colorado and San Antonio, Texas, we measured CT‐derived visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and visceral:subcutaneous ratio (VSR). A genome‐wide association study (GWAS) was completed using the Illumina HumanHap 300 BeadChip (～317K single‐nucleotide polymorphisms (SNPs)) in 229 individuals from the San Antonio site (stage 1). In total, 297 SNPs with evidence for association with VAT, SAT, or VSR, adjusting for age and sex (P < 0.001), were genotyped in the remaining 961 Hispanic samples. The entire Hispanic cohort (n = 1,190) was then tested for association, adjusting for age, sex, site of recruitment, and admixture estimates (stage 2). In stage 3, additional SNPs were genotyped in four genic regions showing evidence of association in stage 2. Several SNPs were associated in the GWAS (P < 1 × 10^?5) and were confirmed to be significantly associated in the entire Hispanic cohort (P < 0.01), including: rs7543757 for VAT, rs4754373 and rs11212913 for SAT, and rs4541696 and rs4134351 for VSR. Numerous SNPs were associated with multiple adiposity phenotypes. Targeted analysis of four genes whose SNPs were significant in stage 2 suggests candidate genes for influencing the distribution (RGS6) and amount of adiposity (NGEF). Several candidate loci, including RGS6 and NGEF, are associated with CT‐derived adipose fat measures in Hispanic Americans in a three‐stage genetic association study.