Sex-specific genetic architecture of blood pressure

被引：15

作者：

Yang, Min-Lee ^{[1
,2
,3
]}

Xu, Chang ^{[4
,5
]}

Gupte, Trisha ^{[1
]}

Hoffmann, Thomas J. ^{[6
,7
]}

Iribarren, Carlos ^{[8
]}

Zhou, Xiang ^{[4
,5
]}

Ganesh, Santhi K. ^{[1
,2
,3
]}

机构：

[1] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48105 USA

[2] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48105 USA

[3] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48105 USA

[4] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI USA

[5] Univ Michigan, Ctr Stat Genet, Sch Publ Hlth, Ann Arbor, MI USA

[6] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA USA

[7] Univ Calif San Francisco, Inst Human Genet, Sch Med, San Francisco, CA USA

[8] Kaiser Permanente, Div Res, Oakland, CA USA

来源：

NATURE MEDICINE | 2024年 / 30卷 / 03期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; HORMONE-THERAPY; VARIANTS; LOCI; RISK; HYPERTENSION; MORTALITY; ADULTS; ALPHA; HEART;

D O I：

10.1038/s41591-024-02858-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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 (P-female <= 5 x 10(-8); P-male > 5 x 10(-8)) and 142 were male-specific (P-male <= 5 x 10(-8); P-female > 5 x 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

页码：818 / 828

页数：11

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