Your browser doesn't support javascript.
loading
Association of PHACTR1 with Coronary Artery Calcium Differs by Sex and Cigarette Smoking.
Voorhies, Kirsten; Young, Kendra; Hsu, Fang-Chi; Palmer, Nicholette D; McDonald, Merry-Lynn N; Lee, Sanghun; Hahn, Georg; Hecker, Julian; Prokopenko, Dmitry; Wu, Ann Chen; Regan, Elizabeth A; DeMeo, Dawn; Kinney, Greg L; Crapo, James D; Cho, Michael H; Silverman, Edwin K; Lange, Christoph; Budoff, Matthew J; Hokanson, John E; Lutz, Sharon M.
Afiliación
  • Voorhies K; Department of Population Medicine, Harvard Pilgrim Health Care Institute, Boston, MA 02115, USA.
  • Young K; Department of Epidemiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Hsu FC; Department of Biostatistics and Data Science, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA.
  • Palmer ND; Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA.
  • McDonald MN; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35212, USA.
  • Lee S; Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
  • Hahn G; Division of Medicine, Department of Medical Consilience, Graduate School, Dankook University, Yongin 16890, Republic of Korea.
  • Hecker J; Brigham and Women's Hospital, Division of Pharmacoepidemiology and Pharmacoeconomics, and Department of Medicine, Harvard Medical School, Boston, MA 02120, USA.
  • Prokopenko D; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Wu AC; Genetics and Aging Research Unit and the McCance Center for Brain Health, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Regan EA; Department of Population Medicine, Harvard Pilgrim Health Care Institute, Boston, MA 02115, USA.
  • DeMeo D; Department of Medicine, National Jewish Health, Denver, CO 80206, USA.
  • Kinney GL; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Crapo JD; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Cho MH; Department of Epidemiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Silverman EK; Department of Medicine, National Jewish Health, Denver, CO 80206, USA.
  • Lange C; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Budoff MJ; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Hokanson JE; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Lutz SM; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
J Cardiovasc Dev Dis ; 11(7)2024 Jun 27.
Article en En | MEDLINE | ID: mdl-39057616
ABSTRACT

Background:

Coronary artery calcium (CAC) is a marker of subclinical atherosclerosis and is a complex heritable trait with both genetic and environmental risk factors, including sex and smoking.

Methods:

We performed genome-wide association (GWA) analyses for CAC among all participants and stratified by sex in the COPDGene study (n = 6144 participants of European ancestry and n = 2589 participants of African ancestry) with replication in the Diabetes Heart Study (DHS). We adjusted for age, sex, current smoking status, BMI, diabetes, self-reported high blood pressure, self-reported high cholesterol, and genetic ancestry (as summarized by principal components computed within each racial group). For the significant signals from the GWA analyses, we examined the single nucleotide polymorphism (SNP) by sex interactions, stratified by smoking status (current vs. former), and tested for a SNP by smoking status interaction on CAC.

Results:

We identified genome-wide significant associations for CAC in the chromosome 9p21 region [CDKN2B-AS1] among all COPDGene participants (p = 7.1 × 10-14) and among males (p = 1.0 × 10-9), but the signal was not genome-wide significant among females (p = 6.4 × 10-6). For the sex stratified GWA analyses among females, the chromosome 6p24 region [PHACTR1] had a genome-wide significant association (p = 4.4 × 10-8) with CAC, but this signal was not genome-wide significant among all COPDGene participants (p = 1.7 × 10-7) or males (p = 0.03). There was a significant interaction for the SNP rs9349379 in PHACTR1 with sex (p = 0.02), but the interaction was not significant for the SNP rs10757272 in CDKN2B-AS1 with sex (p = 0.21). In addition, PHACTR1 had a stronger association with CAC among current smokers (p = 6.2 × 10-7) than former smokers (p = 7.5 × 10-3) and the SNP by smoking status interaction was marginally significant (p = 0.03). CDKN2B-AS1 had a strong association with CAC among both former (p = 7.7 × 10-8) and current smokers (p = 1.7 × 10-7) and the SNP by smoking status interaction was not significant (p = 0.40).

Conclusions:

Among current and former smokers of European ancestry in the COPDGene study, we identified a genome-wide significant association in the chromosome 6p24 region [PHACTR1] with CAC among females, but not among males. This region had a significant SNP by sex and SNP by smoking interaction on CAC.
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Cardiovasc Dev Dis Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Cardiovasc Dev Dis Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza