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Genome‐Wide Association Analysis Identified Candidate Variants Associated With Responsiveness to a Blood Pressure Reduction Intervention in Rural North Carolina
Author(s) -
Lenhart Kaitlin Christine,
Robasky Kimberly,
Jones Wendell,
Halladay Jacqueline,
Ammerman Alice,
Patterson Cam,
Schisler Jonathan Cummings
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1177.15
Subject(s) - blood pressure , medicine , cohort , single nucleotide polymorphism , genome wide association study , obesity , population , gerontology , demography , genetics , environmental health , biology , genotype , sociology , gene
Lenoir County, North Carolina, is among the poorest in the state with significantly elevated incidences of heart disease, stroke, and obesity relative to state and national levels. We developed the Heart Healthy Lenoir project (an NHLBI‐funded Center for Population Health and Health Disparities) to create long‐term, sustainable approaches to reducing cardiovascular disease risk disparities in Lenoir County, with a focus on controlling hypertension and promoting healthy lifestyle changes. Complementing our clinical interventions, we genotyped 347 study participants utilizing genome‐wide technologies to identify genetic‐based factors that contribute to increased cardiovascular disease (CVD) risk, with a particular focus on hypertension and obesity. Among the 124 Caucasian (CAU) and 193 African American (AA) study participants, we observed a marked reduction in systolic blood pressure (SBP) one year following initiation of the intervention (−6.28 mmHg ± 1.25 and −4.52 mmHg ± 1.16 in CAU and AA groups, respectively). We also observed a modest reduction in body weight (−1.09 kg ± 0.36 and −0.91 kg ± 0.29 in CAU and AA groups, respectively). A workflow was established to identify problematic single nucleotide polymorphisms (SNPs), potential problematic samples, and subsequent optimization of genotyping calls based on the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium that resulted in 585,865 SNPs used in our analyses. We developed a linear model accounting for age, gender and smoking status in the African American cohort: ΔSBP 12‐month ~ Age + Gender + Smoking + Gender*Age + Smoked*Age + SNP + SNP*Age. The resulting Q‐Q plot identified a skewed region that we filtered for p‐values < 0.0001 resulting in the identification of 46 loci with low p‐values for both the homozygous SNP term and the interaction term associated with SBP reduction at one year post‐intervention. Interestingly, we found 7 SNPs mapped to 3 separate loci linked to 6 candidate genes (CELF2, SFTA1P, CHST9, AQP4, CPVL, and CHN2) that may be involved in CVD risk and inflammation. It is important to note that our study is limited by cohort size power and further investigation is required to delineate these associations and responsiveness to hypertension interventions, however, our data identified novel genetic loci associated with positive intervention implementation in a rural North Carolinian cohort.