TY - JOUR
T1 - Body mass index modulates blood pressure heritability
T2 - The family blood pressure program
AU - Simino, Jeannette
AU - Shi, Gang
AU - Weder, Alan
AU - Boerwinkle, Eric
AU - Hunt, Steven C.
AU - Rao, Dabeeru C.
N1 - Funding Information:
We thank all the participants in GenNet, GENOA, HyperGEN, and SAPPHIRe. This research was partly supported by grants T32 HL091823, U01 HL54473, R21 HL095054, and R01 GM28719 from the National Heart, Lung, and Blood Institute. The authors fondly acknowledge the late J. David Curb for his assistance with the manuscript. The following investigators are associated with the Family Blood Pressure Program: GenNet Network: Alan B. Weder (Network Director), Lillian Gleiberman (Network Coordinator), Anne E. Kwitek, Aravinda Chakravarti, Richard S. Cooper, Carolina Delgado, Howard J. Jacob, and Nicholas J. Schork. GENOA Network: Eric Boerwinkle (Network Director), Tom Mosley, Alanna Morrison, Kathy Klos, Craig Hanis, Sharon Kardia, and Stephen Turner. HyperGEN Network: Steven C. Hunt (Network Director), Janet Hood, Donna Arnett, John H. Eckfeldt, R. Curtis Ellison, Chi Gu, Gerardo Heiss, Paul Hopkins, Aldi Kraja, Jean-Marc Lalouel, Mark Leppert, Albert Oberman, Michael A. Province, D. C. Rao, Treva Rice, and Robert Weiss. SAPPHIRe Network: David Curb (former Network Director), David Cox, Timothy Donlon, Victor Dzau, John Grove, Kamal Masaki, Richard Myers, Richard Olshen, Richard Pratt, Tom Quertermous, Neil Risch, and Beatriz Rodriguez. National Heart, Lung, and Blood Institute: Dina Paltoo and Cashell E. Jaquish.
PY - 2014/4
Y1 - 2014/4
N2 - BACKGROUND: Candidate gene and twin studies suggest that interactions between body mass index (BMI) and genes contribute to the variability of blood pressure (BP). To determine whether there is evidence for gene-BMI interactions, we investigated the modulation of BP heritability by BMI using 4,153 blacks, 1,538 Asians, 4,013 whites, and 2,199 Hispanic Americans from the Family Blood Pressure Program. METHODS: To capture the BP heritability dependence on BMI, we employed a generalized variance components model incorporating linear and Gaussian interactions between BMI and the genetic component. Within each race and network subgroup, we used the Akaike information criterion and likelihood ratio test to select the appropriate interaction function for each BP trait (systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP)) and determine interaction significance, respectively. RESULTS: BP heritabilities were significantly modified by BMI in the GenNet and SAPPHIRe Networks, which contained the youngest and least-obese participants, respectively. GenNet Whites had unimodal SBP, MAP, and PP heritabilities that peaked between BMI values of 33 and 37kg/m2. The SBP and MAP heritabilities in GenNet Hispanic Americans, as well as the PP heritability in GenNet blacks, were increasing functions of BMI. The DBP and SBP heritabilities in the SAPPHIRe Chinese and Japanese, respectively, were decreasing functions of BMI. CONCLUSIONS: BP heritability differed by BMI in the youngest and least-obese networks, although the shape of this dependence differed by race. Use of nonlinear gene-BMI interactions may enhance BP gene discovery efforts in individuals of European ancestry.
AB - BACKGROUND: Candidate gene and twin studies suggest that interactions between body mass index (BMI) and genes contribute to the variability of blood pressure (BP). To determine whether there is evidence for gene-BMI interactions, we investigated the modulation of BP heritability by BMI using 4,153 blacks, 1,538 Asians, 4,013 whites, and 2,199 Hispanic Americans from the Family Blood Pressure Program. METHODS: To capture the BP heritability dependence on BMI, we employed a generalized variance components model incorporating linear and Gaussian interactions between BMI and the genetic component. Within each race and network subgroup, we used the Akaike information criterion and likelihood ratio test to select the appropriate interaction function for each BP trait (systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP)) and determine interaction significance, respectively. RESULTS: BP heritabilities were significantly modified by BMI in the GenNet and SAPPHIRe Networks, which contained the youngest and least-obese participants, respectively. GenNet Whites had unimodal SBP, MAP, and PP heritabilities that peaked between BMI values of 33 and 37kg/m2. The SBP and MAP heritabilities in GenNet Hispanic Americans, as well as the PP heritability in GenNet blacks, were increasing functions of BMI. The DBP and SBP heritabilities in the SAPPHIRe Chinese and Japanese, respectively, were decreasing functions of BMI. CONCLUSIONS: BP heritability differed by BMI in the youngest and least-obese networks, although the shape of this dependence differed by race. Use of nonlinear gene-BMI interactions may enhance BP gene discovery efforts in individuals of European ancestry.
KW - BMI
KW - Blood pressure
KW - FBPP
KW - Heritability
KW - Hypertension
KW - Interactions
UR - http://www.scopus.com/inward/record.url?scp=84897837676&partnerID=8YFLogxK
U2 - 10.1093/ajh/hpt144
DO - 10.1093/ajh/hpt144
M3 - Article
C2 - 24029162
AN - SCOPUS:84897837676
SN - 0895-7061
VL - 27
SP - 610
EP - 619
JO - American Journal of Hypertension
JF - American Journal of Hypertension
IS - 4
ER -