TY - JOUR
T1 - Gene-education interactions identify novel blood pressure loci in the framingham heart study
AU - Basson, Jacob
AU - Sung, Yun Ju
AU - Schwander, Karen
AU - Kume, Rezart
AU - Simino, Jeannette
AU - De Las Fuentes, Lisa
AU - Rao, Dabeeru
N1 - Funding Information:
We thank all participants of the Framingham Heart Study for their dedication to cardiovascular health research. Our investigation was supported by grant R01 HL107552 from the National Heart, Lung, and Blood Institute (NHLBI). The Framingham Heart Study is conducted and supported by the NHLBI in collaboration with Boston University (Contract No. N01-HC-25195). Funding for SHARe Affymetrix geno-typing was provided by NHLBI Contract N02-HL-64278. 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 the NHLBI.
PY - 2014/3
Y1 - 2014/3
N2 - BACKGROUNDBlood pressure (BP) variability has a genetic component, most of which has yet to be attributed to specific variants. One promising strategy for gene discovery is analysis of interactions between single-nucleotide polymorphisms (SNPs) and BP-related factors, including age, sex, and body mass index (BMI). Educational attainment, a marker for socioeconomic status, has effects on both BP and BMI.METHODSWe investigated SNP-education interaction effects on BP in genome-wide data on 3,836 subjects in families from the Framingham Heart Study. The ABEL suite was used to adjust for age, sex, BMI, medication use, and kinship and to perform 1 degree-of-freedrom (df) and 2 df SNP-education interaction tests.RESULTSAn SNP in PTN was associated with increased systolic BP (5.4mm Hg per minor allele) in those without a bachelor's degree but decreased systolic BP (1.6mm Hg per allele) in those with a bachelor's degree (2 df; P = 2.08×10-8). An SNP in TOX2 was associated with increased diastolic BP (DBP; 4.1mm Hg per minor allele) in those with no more educational attainment than high school but decreased DBP in those with education past high school (-0.7; 1 df; P = 3.74×10-8). Three suggestive associations were also found: in MYO16 (pulse pressure: 2 df; P = 2.89×10-7), in HAS2 (DBP: 1 df; P = 1.41×10 -7), and in DLEU2 (DBP: 2 df; P = 1.93×10-7). All 5 genes are related to BP, including roles in vasodilation and angiogenesis for PTN and TOX2.CONCLUSIONSPTN and TOX2 are associated with BP. Analyzing SNP-education interactions may detect novel associations. Education may be a surrogate for unmeasured exposures and behaviors modifying SNP effects on BP.
AB - BACKGROUNDBlood pressure (BP) variability has a genetic component, most of which has yet to be attributed to specific variants. One promising strategy for gene discovery is analysis of interactions between single-nucleotide polymorphisms (SNPs) and BP-related factors, including age, sex, and body mass index (BMI). Educational attainment, a marker for socioeconomic status, has effects on both BP and BMI.METHODSWe investigated SNP-education interaction effects on BP in genome-wide data on 3,836 subjects in families from the Framingham Heart Study. The ABEL suite was used to adjust for age, sex, BMI, medication use, and kinship and to perform 1 degree-of-freedrom (df) and 2 df SNP-education interaction tests.RESULTSAn SNP in PTN was associated with increased systolic BP (5.4mm Hg per minor allele) in those without a bachelor's degree but decreased systolic BP (1.6mm Hg per allele) in those with a bachelor's degree (2 df; P = 2.08×10-8). An SNP in TOX2 was associated with increased diastolic BP (DBP; 4.1mm Hg per minor allele) in those with no more educational attainment than high school but decreased DBP in those with education past high school (-0.7; 1 df; P = 3.74×10-8). Three suggestive associations were also found: in MYO16 (pulse pressure: 2 df; P = 2.89×10-7), in HAS2 (DBP: 1 df; P = 1.41×10 -7), and in DLEU2 (DBP: 2 df; P = 1.93×10-7). All 5 genes are related to BP, including roles in vasodilation and angiogenesis for PTN and TOX2.CONCLUSIONSPTN and TOX2 are associated with BP. Analyzing SNP-education interactions may detect novel associations. Education may be a surrogate for unmeasured exposures and behaviors modifying SNP effects on BP.
KW - GWAS
KW - blood pressure
KW - educational attainment
KW - gene-education interaction
KW - hypertension
KW - interaction
UR - http://www.scopus.com/inward/record.url?scp=84894226290&partnerID=8YFLogxK
U2 - 10.1093/ajh/hpt283
DO - 10.1093/ajh/hpt283
M3 - Article
C2 - 24473254
AN - SCOPUS:84894226290
SN - 0895-7061
VL - 27
SP - 431
EP - 444
JO - American Journal of Hypertension
JF - American Journal of Hypertension
IS - 3
ER -