Sex-specific genetic architecture of blood pressure

被引:0
|
作者
Min-Lee Yang
Chang Xu
Trisha Gupte
Thomas J. Hoffmann
Carlos Iribarren
Xiang Zhou
Santhi K. Ganesh
机构
[1] University of Michigan,Department of Internal Medicine, Division of Cardiovascular Medicine
[2] University of Michigan,Department of Human Genetics
[3] University of Michigan,Department of Computational Medicine and Bioinformatics
[4] University of Michigan School of Public Health,Department of Biostatistics
[5] University of Michigan School of Public Health,Center for Statistical Genetics
[6] University of California,Department of Epidemiology & Biostatistics, and Institute for Human Genetics, School of Medicine
[7] San Francisco,Division of Research
[8] Kaiser Permanente,undefined
来源
Nature Medicine | 2024年 / 30卷
关键词
D O I
暂无
中图分类号
学科分类号
摘要
The genetic and genomic basis of sex differences in blood pressure (BP) traits remain unstudied at scale. Here, we conducted sex-stratified and combined-sex genome-wide association studies of BP traits using the UK Biobank resource, identifying 1,346 previously reported and 29 new BP trait-associated loci. Among associated loci, 412 were female-specific (Pfemale ≤ 5 × 10−8; Pmale > 5 × 10−8) and 142 were male-specific (Pmale ≤ 5 × 10−8; Pfemale > 5 × 10−8); these sex-specific loci were enriched for hormone-related transcription factors, in particular, estrogen receptor 1. Analyses of gene-by-sex interactions and sexually dimorphic effects identified four genomic regions, showing female-specific associations with diastolic BP or pulse pressure, including the chromosome 13q34-COL4A1/COL4A2 locus. Notably, female-specific pulse pressure-associated loci exhibited enriched acetylated histone H3 Lys27 modifications in arterial tissues and a female-specific association with fibromuscular dysplasia, a female-biased vascular disease; colocalization signals included Chr13q34: COL4A1/COL4A2, Chr9p21: CDKN2B-AS1 and Chr4q32.1: MAP9 regions. Sex-specific and sex-biased polygenic associations of BP traits were associated with multiple cardiovascular traits. These findings suggest potentially clinically significant and BP sex-specific pleiotropic effects on cardiovascular diseases.
引用
收藏
页码:818 / 828
页数:10
相关论文
共 50 条
  • [21] Sex-specific trajectories of systolic and diastolic blood pressure in youth
    Sylvestre, Marie-Pierre
    Ka, Khady
    Dugas, Erika N.
    Zappitelli, Michael
    O'Loughlin, Jennifer
    JOURNAL OF HYPERTENSION, 2017, 35 (07) : 1416 - 1423
  • [22] The Sex-Specific Impact of Aging on the Blood Pressure Response to Exercise
    Trinity, Joel Douglas
    Layec, Gwenael
    Hart, Corey R.
    Richardson, Russell S.
    FASEB JOURNAL, 2017, 31
  • [23] SEX-SPECIFIC AND SEX-LINKED INFLUENCES ON BLOOD-PRESSURE IN THE SHR
    TROLLIET, MR
    KRIEGER, JE
    KOIKE, G
    SIMON, J
    KRIEGER, EM
    STEC, D
    ROMAN, R
    LANDER, ES
    DZAU, VJ
    JACOB, HJ
    HYPERTENSION, 1995, 25 (06) : 1375 - 1375
  • [24] Exploring sex-specific genetic architecture of coronary artery disease in Tehran: a cardiometabolic genetic study
    Najd-Hassan-Bonab, Leila
    Daneshpour, Maryam S.
    Jafarinia, Mojtaba
    Akbarzadeh, Mahdi
    Moazzam-Jazi, Maryam
    Asgarian, Sara
    Khalili, Davood
    EXPERT REVIEW OF MOLECULAR DIAGNOSTICS, 2024, 24 (12) : 1171 - 1180
  • [25] Sex-specific relationships of inflammatory biomarkers with blood pressure in older adults
    Sulicka-Grodzicka, Joanna
    Wizner, Barbara
    Zdrojewski, Tomasz
    Mossakowska, Malgorzata
    Puzianowska-Kuznicka, Monika
    Chudek, Jerzy
    Wiecek, Andrzej
    Korkosz, Mariusz
    Caiazzo, Elisabetta
    Maffia, Pasquale
    Siedlinski, Mateusz
    Messerli, Franz H.
    Guzik, Tomasz J.
    GEROSCIENCE, 2024, 46 (5) : 4603 - 4614
  • [26] GENETIC DETERMINATION OF SEX-SPECIFIC ANTIGENS
    FOX, AS
    JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1959, 23 (06): : 1297 - +
  • [27] Homozygosity by descent mapping of blood pressure in the Old Order Amish: evidence for sex specific genetic architecture
    Patrick F McArdle
    Harvey Dytch
    Jeffery R O'Connell
    Alan R Shuldiner
    Braxton D Mitchell
    Mark Abney
    BMC Genetics, 8
  • [28] Homozygosity by descent mapping of blood pressure in the Old Order Amish: evidence for sex specific genetic architecture
    McArdle, Patrick F.
    Dytch, Harvey
    O'Connell, Jeffery R.
    Shuldiner, Alan R.
    Mitchell, Braxton D.
    Abney, Mark
    BMC GENETICS, 2007, 8 (1)
  • [29] Rapid sex-specific evolution of age at maturity is shaped by genetic architecture in Atlantic salmon
    Czorlich, Yann
    Aykanat, Tutku
    Erkinaro, Jaakko
    Orell, Panu
    Primmer, Craig Robert
    NATURE ECOLOGY & EVOLUTION, 2018, 2 (11): : 1800 - 1807
  • [30] Rapid Evolution of Lifespan in a Novel Environment: Sex-Specific Responses and Underlying Genetic Architecture
    Charles W. Fox
    James D. Wagner
    Sara Cline
    Frances Ann Thomas
    Frank J. Messina
    Evolutionary Biology, 2011, 38 : 182 - 196