African ancestry and lung function in Puerto Rican children

Abstract

Background Puerto Ricans and African Americans share a significant proportion of African ancestry. Recent findings suggest that African ancestry influences lung function in African American adults. Objective To examine whether a greater proportion of African ancestry is associated with lower FEV1 and FVC in Puerto Rican children, independently of socioeconomic status (SES), healthcare access or key environmental/lifestyle (EL) factors. Methods Cross-sectional case-control study of 943 Puerto Rican children ages 6 to 14 years with (n=520) and without (n=423) asthma (defined as physician-diagnosed asthma and wheeze in the prior year) living in Hartford (CT, n=383) and San Juan (PR, n=560). We estimated the percentage of African racial ancestry in study participants using genome-wide genotypic data. We tested whether African ancestry is associated with FEV1 and FVC using linear regression. Multivariate models were adjusted for indicators of SES and healthcare, and selected EL exposures. Results After adjustment for household income and other covariates, each 20% increment in African ancestry was significantly associated with lower pre-bronchodilator(BD) FEV1 (−105 ml, 95% confidence interval [CI] = −159 ml to −51 ml, P <0.001) and FVC (−133 ml, 95% CI −197 ml to −69 ml, P <0.001), and post-BD FEV1 (−152 ml, 95% CI=−210 ml to −94 ml, P <0.001) and FVC (−145 ml, 95% CI= −211 to −79 ml, P <0.001) in children with asthma. Similar but weaker associations were found for pre- and post-BD FEV1 (change for each 20% increment in African ancestry= −78 ml, 95% CI= −131 to −25 ml, P=0.004), and for post-BD FVC among children without asthma. Conclusions Genetic and/or EL factors correlated with African ancestry may influence childhood lung function in Puerto Ricans.

ADCYAP1R1 and Asthma in Puerto Rican Children

“…After excluding 66 subjects without sufficient DNA for the pyrosequencing assay (n ¼ 44) or who failed quality control for our genome-wide association study (20) (e.g., sex mismatch, duplicate samples [n ¼ 22]), 517 (89%) of the 583 participants remained in this analysis, comprising 272 children with asthma (cases) and 245 children without asthma. One case in San Juan had extremely high methylation at the CpG site of interest (z20%, confirmed in additional replication experiments; all other samples had methylation levels between 0.4% and 6.1% [see Figure E2]) and was excluded from all primary analyses to avoid losing generalizability of the models (despite obtaining similar results when including this subject [see Table E2]).…”

“…Logistic regression was used for the multivariate analysis of methylation at the ADCYAP1R1 CpG site (expressed as a percentage) and asthma (physician-diagnosed and wheeze in the prior year). Because of their potential association with DNA methylation or asthma in Puerto Rican children, the following covariates were included in all multivariate models: age, sex, household income (, vs. >$15,000 [near the median income for households in Puerto Rico in 2008-2009 (21)]), and principal components (22) (calculated from available genome-wide genotypic data (20) [using EIGENSTRAT (22)] to adjust for potential population stratification caused by differences in DNA methylation and asthma prevalence among ancestral populations for Puerto Ricans [20]). …”

“…Although we have genome-wide genotypic data in study participants (20), the single nucleotide polymorphism (SNP) in ADCYAP1R1 that has been implicated in PTSD and childhood anxiety (rs2267735) is neither included in our genotyping platform (HumanOmni2.5 BeadChip; Illumina, Inc, San Diego, CA) nor in moderate-to-high linkage disequilibrium (r 2 > 0.6) with any SNP in that platform. We thus genotyped SNP rs2267735 using the TaqMan 59 exonuclease assay (Life Technologies, Carlsbad, CA) using primers provided by ABI (ABI, Foster City, CA).…”

A Genome-Wide Association Study of Post-bronchodilator Lung Function in Children with Asthma

“…From September 2003 to June 2010, 618 children with asthma (physician-diagnosed asthma and one or more episode of wheeze in the previous year) were recruited in Hartford, Connecticut (n = 267), and San Juan, Puerto Rico (n = 351), as described elsewhere (11). At both study sites, eligibility criteria included age 6-14 years and having four Puerto Rican grandparents.…”

“…The best FEV 1 and FVC from each test were selected for analysis. Of the 618 participants, 560 had blood samples and sufficient DNA for genome-wide genotyping, conducted using the HumanOmni2.5 BeadChip platform (Illumina Inc., San Diego, CA), as previously described (11). After excluding subjects with low marker call rate (n = 31), sex mismatch (n = 6), or missing post-BD phenotypes (n = 76), 447 subjects remained in the analysis.…”