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期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-02858-2

摘要内容如下：

血压（BP）性状性别差异的遗传和基因组基础仍未大规模研究。在这里，我们利用英国生物库资源对BP性状进行了性别分层和组合性别全基因组关联研究，确定了1，346个先前报道的和29个新的BP性状相关基因座。在相关位点中，有412个为女性特有（Pfemale≤5×10-8；PMALER>5×10-8）和142为雄性特异性（PMALER≤5×10-8；Pfemale>5×10-8）；这些性别特异性基因座富含激素相关转录因子，特别是雌激素受体1。对基因-性别相互作用和两性异形效应的分析确定了四个基因组区域，显示女性特异性与舒张压或脉压相关，包括染色体13q34-COL4A1/COL4A2基因座。值得注意的是，女性特异性脉压相关基因座在动脉组织中表现出丰富的乙酰化组蛋白H3 Lys27修饰，并且女性特异性与纤维肌肉发育不良（一种偏向女性的血管疾病）相关；共定位信号包括CHR13q34:COL4A1/COL4A2，CHR9p21:CDKN2B-AS1和CHR4q32.1:MAP9区域。血压性状的性别特异性和性别偏向性多基因关联与多种心血管性状相关。这些发现表明，BP对心血管疾病具有潜在的临床意义和性别特异性多效性。

英文原文如下：

Abstracts

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.

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