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
","abstract_html":"<p>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</p>","abstract_has_math":false,"creators":["Basson, Jacob John"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Biology and Biomedical Sciences: Human and Statistical Genetics","degree_department":null,"school":null,"contributors":["Dabeeru C Rao"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-09-03T07:00:00Z","date_published":"2013-09-03T07:00:00Z","updated_at":"2026-07-24T06:12:48Z","subjects":["Blood pressure","Interactions","SNP"],"languages":["English (en)"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.7936/K7MW2F55"],"render_values":[{"text":"https://doi.org/10.7936/K7MW2F55","href":"https://doi.org/10.7936/K7MW2F55","code":true}]}]},"links":{"outbound_url":"https://openscholarship.wustl.edu/etd/1119","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Dabeeru C Rao"]},{"key":"dc:creator","label":"Author","values":["Basson, Jacob John"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2014-03-10T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biology and Biomedical Sciences: Human and Statistical Genetics"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Blood pressure","Interactions","SNP"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English (en)"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://openscholarship.wustl.edu/etd/1119"]},{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.7936/K7MW2F55"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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
"]},{"key":"dc:title","label":"Title","values":["SNP Interactions in the Genetic Architecture of Blood Pressure"]}]}],"canonical_facts":{"dc:contributor":["Dabeeru C Rao"],"dc:creator":["Basson, Jacob John"],"dc:date.available":["2014-03-10T07:00:00Z"],"dc:description.abstract":["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
"],"dc:identifier":["https://openscholarship.wustl.edu/etd/1119"],"dc:identifier.doi":["https://doi.org/10.7936/K7MW2F55"],"dc:language":["English (en)"],"dc:subject":["Blood pressure","Interactions","SNP"],"dc:title":["SNP Interactions in the Genetic Architecture of Blood Pressure"],"thesis:degree_discipline":["Biology and Biomedical Sciences: Human and Statistical Genetics"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T06:12:48Z"}