Author's School

Graduate School of Arts & Sciences

Author's Department/Program

Biology and Biomedical Sciences: Human and Statistical Genetics


English (en)

Date of Award

Summer 9-3-2013

Degree Type


Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Dabeeru C Rao


Evidence suggests that there is a substantial genetic component to the regulation of blood pressure: BP) but most BP variance remains unattributed to specific genetic variants. Candidate gene studies show linkage to rare Mendelian disorders but inconsistent association with BP. Massive consortia of genome-wide association studies have identified several dozen loci explaining less than 3% of BP variance. Many explanations have been offered for these observations, of which the current study addresses two: the focus on SNP main effects to the exclusion of interactions, and the low statistical power resulting from the strong multiple-testing burden necessarily imposed when analyzing millions of variants. This study examined the role of interactions among a limited set of variants: 818 SNPs in 70 genes) drawn from two broad signaling pathways: renal ion balance and inflammation. Exhaustive SNP-SNP interaction testing was performed, as was analysis of SNP-sex, SNP-BMI, and SNP-hypertension interactions. In hypertensive subjects only, rs12821401 in ADIPOR2 was significantly associated with SBP: p=6.1e-5). A set of three SNP-SNP interactions among 6 inflammation genes: including ADIPOR2) showed significant evidence of containing one or more true association signals: FDR=4.2%), though no single interaction reached experiment-wise significance. These results provide evidence of a role for SNP-SNP and other SNP interactions and implicate an inflammation gene, ADIPOR2, not previously associated with hypertension


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