title: Variant Near FGF5 Has Stronger Effects on Blood Pressure in Chinese With a Higher Body Mass Index.
abstract: BACKGROUND
  The objective of this study was to investigate the genetic association of 4 candidate variants with blood pressure and test the modifying effects of environmental factors including age, sex, and body mass index (BMI).
  
  
  METHODS
  We used a linear mixed-effects model to test for variant main effects and variant interactions with age, sex, and BMI on systolic (SBP) and diastolic (DBP) blood pressure in 7,319 Chinese adults from the China Health and Nutrition Survey (CHNS). We attempted to replicate our significant interaction findings in 1,996 Chinese men from the Fangchenggang Area Male Health and Examination Survey (FAMHES).
  
  
  RESULTS
  Two variants (rs11105378 near ATP2B1 and rs1458038 near FGF5) were significantly associated (P < 0.00625 = 0.05/8) with both SBP and DBP in CHNS. Variant rs1378942 near CSK was nominally associated with SBP (P = 0.01). The signal at rs1458038 exhibited a genotype-by-BMI interaction affecting blood pressure (P interaction = 0.0018 for SBP; P interaction = 0.049 for DBP), with the strongest variant effects in those with the highest BMI. In FAMHES, rs1458038 also showed stronger effects on SBP and DBP among men with the highest BMI.
  
  
  CONCLUSIONS
  Our findings suggest high BMI increases the effect of the blood pressure-increasing allele at rs1458038 near FGF5, further highlighting the importance of obesity prevention in reducing hypertension risk.
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Curriculum in Bioinformatics & Computational Biology, University of North Carolina, Chapel Hill, North Carolina, USA;
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China;
authors.forename: Jinxiu
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China;
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA;
authors.forename: Jielin
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA;
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Curriculum in Bioinformatics & Computational Biology, University of North Carolina, Chapel Hill, North Carolina, USA;
authors.forename: Qing
authors.initials: Q
authors.lastname: Duan
authors.affiliation: Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA;
authors.forename: Jingchun
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Curriculum in Bioinformatics & Computational Biology, University of North Carolina, Chapel Hill, North Carolina, USA;
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Lange
authors.affiliation: Carolina Population Center, University of North Carolina, Chapel Hill, North Carolina, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA;
authors.forename: Penny
authors.initials: P
authors.lastname: Gordon-Larsen
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA; Present address: Program for Personalized Cancer Care and Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA (J.X., S.L.Z.); Center for Genomic Translational Medicine and Prevention, Fudan School of Public Health, Fudan University, Shanghai, P.R. China (J.X.); Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, P.R. China (S.L.Z.).
authors.forename: S Lilly
authors.initials: SL
authors.lastname: Zheng
authors.affiliation: Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China;
authors.forename: Wentao
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China;
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Carolina Population Center, University of North Carolina, Chapel Hill, North Carolina, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA;
authors.forename: Barry M
authors.initials: BM
authors.lastname: Popkin
authors.affiliation: Institute of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China;
authors.forename: Zengnan
authors.initials: Z
authors.lastname: Mo
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA; Present address: Program for Personalized Cancer Care and Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA (J.X., S.L.Z.); Center for Genomic Translational Medicine and Prevention, Fudan School of Public Health, Fudan University, Shanghai, P.R. China (J.X.); Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, P.R. China (S.L.Z.).
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: Carolina Population Center, University of North Carolina, Chapel Hill, North Carolina, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA;
authors.forename: Shufa
authors.initials: S
authors.lastname: Du
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Curriculum in Bioinformatics & Computational Biology, University of North Carolina, Chapel Hill, North Carolina, USA;
authors.forename: Karen L
authors.initials: KL
authors.lastname: Mohlke
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Curriculum in Bioinformatics & Computational Biology, University of North Carolina, Chapel Hill, North Carolina, USA; Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA; elange@med.unc.edu.
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Lange
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D015992:Body Mass Index; D000081247:CSK Tyrosine-Protein Kinase; D002681:China; D005260:Female; D051521:Fibroblast Growth Factor 5 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics*; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009749:Nutrition Surveys; D009765:Obesity / Q000150:complications / Q000235:genetics*; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics*; D055815:Young Adult; D019061:src-Family Kinases / Q000235:genetics*
chemical_list: C506952:ATP2B1 protein, human; C496449:FGF5 protein, human; D051521:Fibroblast Growth Factor 5; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D053499:Plasma Membrane Calcium-Transporting ATPases
keywords: BMI; FGF5; blood pressure; hypertension; interaction.