title: Imputing observed blood pressure for antihypertensive treatment: impact on population and genetic analyses.
abstract: BACKGROUND
  Elevated blood pressure (BP), a heritable risk factor for many age-related disorders, is commonly investigated in population and genetic studies, but antihypertensive use can confound study results. Routine methods to adjust for antihypertensives may not sufficiently account for newer treatment protocols (i.e., combination or multiple drug therapy) found in contemporary cohorts.
  
  
  METHODS
  We refined an existing method to impute unmedicated BP in individuals on antihypertensives by incorporating new treatment trends. We assessed BP and antihypertensive use in male twins (n = 1,237) from the Vietnam Era Twin Study of Aging: 36% reported antihypertensive use; 52% of those treated were on multiple drugs.
  
  
  RESULTS
  Estimated heritability was 0.43 (95% confidence interval (CI) = 0.20-0.50) and 0.44 (95% CI = 0.22-0.61) for measured systolic BP (SBP) and diastolic BP (DBP), respectively. We imputed BP for antihypertensives by 3 approaches: (i) addition of a fixed value of 10/5mm Hg to measured SBP/DBP; (ii) incremented addition of mm Hg to BP based on number of medications; and (iii) a refined approach adding mm Hg based on antihypertensive drug class and ethnicity. The imputations did not significantly affect estimated heritability of BP. However, use of our most refined imputation method and other methods resulted in significantly increased phenotypic correlations between BP and body mass index, a trait known to be correlated with BP.
  
  
  CONCLUSIONS
  This study highlights the potential usefulness of applying a representative adjustment for medication use, such as by considering drug class, ethnicity, and the combination of drugs when assessing the relationship between BP and risk factors.
authors.affiliation: Department of Psychiatry, University of California-San Diego, La Jolla, California, USA.
authors.forename: Brinda K
authors.initials: BK
authors.lastname: Rana
authors.forename: Anish
authors.initials: A
authors.lastname: Dhamija
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Panizzon
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Spoon
authors.forename: Terrie
authors.initials: T
authors.lastname: Vasilopoulos
authors.forename: Carol E
authors.initials: CE
authors.lastname: Franz
authors.forename: Michael D
authors.initials: MD
authors.lastname: Grant
authors.forename: Kristen C
authors.initials: KC
authors.lastname: Jacobson
authors.forename: Kathleen
authors.initials: K
authors.lastname: Kim
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lyons
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: McCaffery
authors.forename: Phyllis K
authors.initials: PK
authors.lastname: Stein
authors.forename: Hong
authors.initials: H
authors.lastname: Xian
authors.forename: Daniel T
authors.initials: DT
authors.lastname: O'Connor
authors.forename: William S
authors.initials: WS
authors.lastname: Kremen
mesh_terms: D000465:Algorithms; D000704:Analysis of Variance; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics; D015992:Body Mass Index; D015986:Confounding Factors, Epidemiologic; D004200:Diseases in Twins / Q000175:diagnosis / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics; D004359:Drug Therapy, Combination; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D017711:Nonlinear Dynamics; D010641:Phenotype; D011159:Population Surveillance; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D014744:Vietnam / Q000453:epidemiology
chemical_list: D000959:Antihypertensive Agents
keywords: VETSA.; antihypertensive; blood pressure; body mass index; heritability; hypertension; twins