期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 43, 页码 11018-11023出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1809872115
关键词
genome-wide association; erectile dysfunction; SIM1; genetic; melanocortin
资金
- National Institute on Aging, National Institute of Mental Health (NIMH)
- National Institute of Health Common Fund [RC2 AG036607]
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01 DK104764]
- National Eye Institute [R01 EY027004]
- NIDDK [1R01DK090382]
- UCSF School of Pharmacy 2017 Mary Anne Koda-Kimble Seed Award for Innovation
- National Human Genome Research Institute [1UM1HG009408]
- NIMH [1R01MH109907]
- National Institute of Child and Human Development [1P01HD084387]
- National Heart, Lung, and Blood Institute [1R01HL138424]
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [P01HD084387] Funding Source: NIH RePORTER
- NATIONAL EYE INSTITUTE [R01EY027004] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL138424] Funding Source: NIH RePORTER
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [UM1HG009408] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK104764, R01DK090382] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH109907] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [RC2AG036607] Funding Source: NIH RePORTER
Erectile dysfunction affects millions of men worldwide. Twin studies support the role of genetic risk factors underlying erectile dysfunction, but no specific genetic variants have been identified. We conducted a large-scale genome-wide association study of erectile dysfunction in 36,649 men in the multiethnic Kaiser Permanente Northern California Genetic Epidemiology Research in Adult Health and Aging cohort. We also undertook replication analyses in 222,358 men from the UK Biobank. In the discovery cohort, we identified a single locus (rs17185536-T) on chromosome 6 near the single-minded family basic helix-loop-helix transcription factor 1 (SIM1) gene that was significantly associated with the risk of erectile dysfunction (odds ratio = 1.26, P = 3.4 x 10(-25)). The association replicated in the UK Biobank sample (odds ratio = 1.25, P = 6.8 x 10(-14)), and the effect is independent of known erectile dysfunction risk factors, including body mass index (BMI). The risk locus resides on the same topologically associating domain as SIM1 and interacts with the SIM1 promoter, and the rs17185536-T risk allele showed differential enhancer activity. SIM1 is part of the leptin-melanocortin system, which has an established role in body weight homeostasis and sexual function. Because the variants associated with erectile dysfunction are not associated with differences in BMI, our findings suggest a mechanism that is specific to sexual function.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据