Department of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
J Urol. 2020 May;203(5):978-983. doi: 10.1097/JU.0000000000000655. Epub 2019 Nov 15.
Urinary incontinence and fecal incontinence are common disorders in women that negatively impact quality of life. In addition to known health and lifestyle risk factors, genetics may have a role in continence. Identification of genetic variants associated with urinary incontinence and fecal incontinence could result in a better understanding of etiologic pathways, and new interventions and treatments.
We previously generated genome-wide single nucleotide polymorphism data from Nurses' Health Studies participants. The participants provided longitudinal urinary incontinence and fecal incontinence information via questionnaires. Cases of urinary incontinence (6,120) had at least weekly urinary incontinence reported on a majority of questionnaires (3 or 4 across 12 to 16 years) while controls (4,811) consistently had little to no urinary incontinence reported. We classified cases of urinary incontinence in women into stress (1,809), urgency (1,942) and mixed (2,036) subtypes. Cases of fecal incontinence (4,247) had at least monthly fecal incontinence reported on a majority of questionnaires while controls (11,634) consistently had no fecal incontinence reported. We performed a genome-wide association study for each incontinence outcome.
We identified 8 single nucleotide polymorphisms significantly associated (p <5×10) with urinary incontinence located in 2 loci, chromosomes 8q23.3 and 1p32.2. There were no genome-wide significant findings for the urinary incontinence subtype analyses. However, the significant associations for overall urinary incontinence were stronger for the urgency and mixed subtypes than for stress. While no single nucleotide polymorphism reached genome-wide significance for fecal incontinence, 4 single nucleotide polymorphisms had p <10.
Few studies have collected genetic data and detailed urinary incontinence and fecal incontinence information. This genome-wide association study provides initial evidence of genetic associations for urinary incontinence and merits further research to replicate our findings and identify additional risk variants.
尿失禁和粪便失禁是女性常见的疾病，会对生活质量产生负面影响。除了已知的健康和生活方式风险因素外，遗传因素也可能在控制中起作用。鉴定与尿失禁和粪便失禁相关的遗传变异可能会更好地了解病因途径，并为新的干预和治疗方法提供依据。
我们之前从护士健康研究参与者中生成了全基因组单核苷酸多态性数据。参与者通过问卷提供了纵向尿失禁和粪便失禁信息。尿失禁病例（6120 例）在大多数问卷中报告至少每周有尿失禁（12 至 16 年期间有 3 或 4 次），而对照组（4811 例）则始终报告几乎没有尿失禁。我们将女性尿失禁病例分为压力性（1809 例）、急迫性（1942 例）和混合性（2036 例）亚型。粪便失禁病例（4247 例）在大多数问卷中报告至少每月有粪便失禁，而对照组（11634 例）始终报告没有粪便失禁。我们对每个失禁结果进行了全基因组关联研究。
我们在 2 个位点（染色体 8q23.3 和 1p32.2）发现了 8 个与尿失禁显著相关（p<5×10）的单核苷酸多态性。对于尿失禁亚型分析，没有发现全基因组显著结果。然而，对于急迫性和混合性亚型，与压力性亚型相比，整体尿失禁的显著关联更强。虽然没有单个单核苷酸多态性达到粪便失禁的全基因组显著水平，但有 4 个单核苷酸多态性的 p 值小于 10。
很少有研究收集遗传数据和详细的尿失禁和粪便失禁信息。这项全基因组关联研究为尿失禁的遗传关联提供了初步证据，值得进一步研究以复制我们的发现并确定其他风险变异。
