Dataset Information

Cosmopolitan and ethnic-specific replication of genetic risk factors for asthma in 2 Latino populations.

ABSTRACT:

Background

Although Mexicans and Puerto Ricans are jointly classified as "Hispanic/Latino," there are significant differences in asthma prevalence, severity, and mortality between the 2 groups. We sought to examine the possibility that population-specific genetic risks contribute to this disparity.

Objectives

More than 100 candidate genes have been associated with asthma and replicated in an independent population, and 7 genome-wide association studies in asthma have been performed. We compared the pattern of replication of these associations in Puerto Ricans and Mexicans.

Methods

We genotyped Mexican and Puerto Rican trios using an Affymetrix 6.0 GeneChip and used a family-based analysis to test for genetic associations in 124 genes previously associated with asthma.

Results

We identified 32 single nucleotide polymorphisms (SNPs) in 17 genes associated with asthma in at least 1 of the 2 populations. Twenty-two of these SNPs in 11 genes were significantly associated with asthma in the combined population and showed no significant heterogeneity of association, whereas 5 SNPs were associated in only 1 population and showed statistically significant heterogeneity. In a gene-based approach 2 additional genes were associated with asthma in the combined population, and 3 additional genes displayed ethnic-specific associations with heterogeneity.

Conclusions

Our results show that only a minority of genetic association studies replicate in our population of Mexican and Puerto Rican asthmatic subjects. Among SNPs that were successfully replicated, most showed no significant heterogeneity across populations. However, we identified several population-specific genetic associations.

SUBMITTER: Galanter JM

PROVIDER: S-EPMC3129381 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Publications

Cosmopolitan and ethnic-specific replication of genetic risk factors for asthma in 2 Latino populations.

Galanter Joshua M JM Torgerson Dara D Gignoux Christopher R CR Sen Saunak S Roth Lindsey A LA Via Marc M Aldrich Melinda C MC Eng Celeste C Huntsman Scott S Rodriguez-Santana Jose J Rodriguez-Cintrón William W Chapela Rocio R Ford Jean G JG Burchard Esteban G EG

The Journal of allergy and clinical immunology 20110528 1

<h4>Background</h4>Although Mexicans and Puerto Ricans are jointly classified as "Hispanic/Latino," there are significant differences in asthma prevalence, severity, and mortality between the 2 groups. We sought to examine the possibility that population-specific genetic risks contribute to this disparity.<h4>Objectives</h4>More than 100 candidate genes have been associated with asthma and replicated in an independent population, and 7 genome-wide association studies in asthma have been performe ...[more]

PMID: 21621256

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Project description:BackgroundHispanic/Latino (HL) populations bear a disproportionately high burden of type 2 diabetes (T2D). The ability to predict T2D genetic risk using polygenic risk scores (PRS) offers great promise for improved screening and prevention. However, there are a number of complications related to the accurate inference of genetic risk across HL populations with distinct ancestry profiles. We investigated how ancestry affects the inference of T2D genetic risk using PRS in diverse HL populations from Colombia and the United States (US). In Colombia, we compared T2D genetic risk for the Mestizo population of Antioquia to the Afro-Colombian population of Chocó, and in the US, we compared European-American versus Mexican-American populations.MethodsWhole genome sequences and genotypes from the 1000 Genomes Project and the ChocoGen Research Project were used for genetic ancestry inference and for T2D polygenic risk score (PRS) calculation. Continental ancestry fractions for HL genomes were inferred via comparison with African, European, and Native American reference genomes, and PRS were calculated using T2D risk variants taken from multiple genome-wide association studies (GWAS) conducted on cohorts with diverse ancestries. A correction for ancestry bias in T2D risk inference based on the frequencies of ancestral versus derived alleles was developed and applied to PRS calculations in the HL populations studied here.ResultsT2D genetic risk in Colombian and US HL populations is positively correlated with African and Native American ancestry and negatively correlated with European ancestry. The Afro-Colombian population of Chocó has higher predicted T2D risk than Antioquia, and the Mexican-American population has higher predicted risk than the European-American population. The inferred relative risk of T2D is robust to differences in the ancestry of the GWAS cohorts used for variant discovery. For trans-ethnic GWAS, population-specific variants and variants with same direction effects across populations yield consistent results. Nevertheless, the control for bias in T2D risk prediction confirms that explicit consideration of genetic ancestry can yield more reliable cross-population genetic risk inferences.ConclusionsT2D associations that replicate across populations provide for more reliable risk inference, and modeling population-specific frequencies of ancestral and derived risk alleles can help control for biases in PRS estimation.

Project description:Studies have suggested that handgrip strength might be a marker for cardiometabolic risk (CMR), but it has not been studied in Hispanic/Latino farmworker population. This study aimed to characterize absolute and relative handgrip strength in Hispanic/Latino farmworkers, and investigate the sex-specific association between handgrip strength and CMR factors. CMR factors and seated isometric absolute (the sum of both hands) and relative (absolute handgrip strength divided by body mass index) handgrip strengths were collected in 173 Hispanic/Latino farmworkers (mean age 35.1 ± 0.7 years; 49% female). The absolute and the relative handgrip strengths were 89.2 ± 1.8 kg, 3.3 ± 0.1 kg among males, and 56.5 ± 1.9 kg, 1.9 ± 0.1 kg among females, respectively. Age was correlated with absolute (r = - 0.17, p = 0.03) and relative handgrip strengths (r = - 0.28, p < 0.01). In males, absolute handgrip was related to triglycerides (r = - 0.25, p < 0.05), whereas relative handgrip was related to waist circumference (r = - 0.32, p < 0.01), waist/hip circumference ratio (r = - 0.36, p < 0.01), high-density lipoprotein (r = 0.24, p < 0.05), and triglycerides (r = - 0.35, p < 0.01). In females, absolute handgrip was related to fasting plasma glucose (r = - 0.28, p = 0.03), whereas relative handgrip was related to waist circumference (r = - 0.38, p < 0.01) and fasting plasma glucose (r = - 0.22, p < 0.05). Males had lower absolute handgrip strength when their triglycerides levels were at risk (p = 0.021), and lower relative handgrip strength when their plasma glucose (p = 0.034) and triglycerides (p = 0.002) levels were at risk. Females had lower relative handgrip strength when their plasma glucose (p = 0.001) and blood pressure (p = 0.004) were at risk. This study suggests that handgrip strength may be associated with sex-specific CMR factors in a Hispanic/Latino farmworker population.

Dataset Information

Cosmopolitan and ethnic-specific replication of genetic risk factors for asthma in 2 Latino populations.

Background

Objectives

Methods

Results

Conclusions

Publications

Cosmopolitan and ethnic-specific replication of genetic risk factors for asthma in 2 Latino populations.

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