TY - JOUR
T1 - Identifying blood pressure loci whose effects are modulated by multiple lifestyle exposures
AU - Osazuwa-Peters, Oyomoare L.
AU - Waken, R. J.
AU - Schwander, Karen L.
AU - Sung, Yun Ju
AU - de Vries, Paul S.
AU - Hartz, Sarah M.
AU - Chasman, Daniel I.
AU - Morrison, Alanna C.
AU - Bierut, Laura J.
AU - Xiong, Chengjie
AU - de las Fuentes, Lisa
AU - Rao, D. C.
N1 - Funding Information:
We thank all participants of the Framingham Heart Study for their dedication to cardiovascular health research. The Framingham Heart Study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University (Contract Nos. N01-HC-25195 and HHSN268201500001I). This manuscript was not prepared in collaboration with investigators of the Framingham Heart Study and does not necessarily reflect the opinions or views of the Framingham Heart Study, Boston University, or NHLBI. This study work was supported by Grants R01HL118305 and T32HL091823 from the National Heart, Lung, and Blood Institute, and NIH Grants R21 AA024888-01 (S. M. H.), and UL1 TR002345 (L. J. B. and S. M. H.). Funding for SHARe Affymetrix genotyping was provided by NHLBI Contract N02-HL-64278. SHARe Illumina genotyping was provided under an agreement between Illumina and Boston University. P. S. D. was additionally supported by American Heart Association grant number 18CDA34110116.
Publisher Copyright:
© 2020 Wiley Periodicals, Inc.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Although multiple lifestyle exposures simultaneously impact blood pressure (BP) and cardiovascular health, most analysis so far has considered each single lifestyle exposure (e.g., smoking) at a time. Here, we exploit gene–multiple lifestyle exposure interactions to find novel BP loci. For each of 6,254 Framingham Heart Study participants, we computed lifestyle risk score (LRS) value by aggregating the risk of four lifestyle exposures (smoking, alcohol, education, and physical activity) on BP. Using the LRS, we performed genome-wide gene–environment interaction analysis in systolic and diastolic BP using the joint 2 degree of freedom (DF) and 1 DF interaction tests. We identified one genome-wide significant (p < 5 × 10−8) and 11 suggestive (p < 1 × 10−6) loci. Gene–environment analysis using single lifestyle exposures identified only one of the 12 loci. Nine of the 12 BP loci detected were novel. Loci detected by the LRS were located within or nearby genes with biologically plausible roles in the pathophysiology of hypertension, including KALRN, VIPR2, SNX1, and DAPK2. Our results suggest that simultaneous consideration of multiple lifestyle exposures in gene–environment interaction analysis can identify additional loci missed by single lifestyle approaches.
AB - Although multiple lifestyle exposures simultaneously impact blood pressure (BP) and cardiovascular health, most analysis so far has considered each single lifestyle exposure (e.g., smoking) at a time. Here, we exploit gene–multiple lifestyle exposure interactions to find novel BP loci. For each of 6,254 Framingham Heart Study participants, we computed lifestyle risk score (LRS) value by aggregating the risk of four lifestyle exposures (smoking, alcohol, education, and physical activity) on BP. Using the LRS, we performed genome-wide gene–environment interaction analysis in systolic and diastolic BP using the joint 2 degree of freedom (DF) and 1 DF interaction tests. We identified one genome-wide significant (p < 5 × 10−8) and 11 suggestive (p < 1 × 10−6) loci. Gene–environment analysis using single lifestyle exposures identified only one of the 12 loci. Nine of the 12 BP loci detected were novel. Loci detected by the LRS were located within or nearby genes with biologically plausible roles in the pathophysiology of hypertension, including KALRN, VIPR2, SNX1, and DAPK2. Our results suggest that simultaneous consideration of multiple lifestyle exposures in gene–environment interaction analysis can identify additional loci missed by single lifestyle approaches.
KW - blood pressure
KW - gene–environment interaction
KW - lifestyle risk score
KW - loci discovery
KW - multiple lifestyle exposures
UR - http://www.scopus.com/inward/record.url?scp=85082458704&partnerID=8YFLogxK
U2 - 10.1002/gepi.22292
DO - 10.1002/gepi.22292
M3 - Article
C2 - 32227373
AN - SCOPUS:85082458704
SN - 0741-0395
VL - 44
SP - 629
EP - 641
JO - Genetic Epidemiology
JF - Genetic Epidemiology
IS - 6
ER -