NDLI: Epigenetic loci for blood pressure are associated with hypertensive target organ damage in older African Americans from the genetic epidemiology network of Arteriopathy (GENOA) study

Content Provider	Springer Nature : BioMed Central
Author	Kho, Minjung Zhao, Wei Ratliff, Scott M. Ammous, Farah Mosley, Thomas H. Shang, Lulu Kardia, Sharon L. R. Zhou, Xiang Smith, Jennifer A.
Abstract	Background Hypertension is a major modifiable risk factor for arteriosclerosis that can lead to target organ damage (TOD) of heart, kidneys, and peripheral arteries. A recent epigenome-wide association study for blood pressure (BP) identified 13 CpG sites, but it is not known whether DNA methylation at these sites is also associated with TOD. Methods In 1218 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study, a cohort of hypertensive sibships, we evaluated the associations between methylation at these 13 CpG sites measured in peripheral blood leukocytes and five TOD traits assessed approximately 5 years later. Results Ten significant associations were found after adjustment for age, sex, blood cell counts, time difference between CpG and TOD measurement, and 10 genetic principal components (FDR q < 0.1): two with estimated glomerular filtration rate (eGFR, cg06690548, cg10601624), six with urinary albumin-to-creatinine ratio (UACR, cg16246545, cg14476101, cg19693031, cg06690548, cg00574958, cg22304262), and two with left ventricular mass indexed to height (LVMI, cg19693031, cg00574958). All associations with eGFR and four associations with UACR remained significant after further adjustment for body mass index (BMI), smoking status, and diabetes. We also found significant interactions between cg06690548 and BMI on UACR, and between 3 CpG sites (cg19693031, cg14476101, and cg06690548) and diabetes on UACR (FDR q < 0.1). Mediation analysis showed that 4.7% to 38.1% of the relationship between two CpG sites (cg19693031 and cg00574958) and two TOD measures (UACR and LVMI) was mediated by blood pressure (Bonferroni-corrected P < 0.05). Mendelian randomization analysis suggests that methylation at two sites (cg16246545 and cg14476101) in PHGDH may causally influence UACR. Conclusions In conclusion, we found compelling evidence for associations between arteriosclerotic traits of kidney and heart and previously identified blood pressure-associated DNA methylation sites. This study may lend insight into the role of DNA methylation in pathological mechanisms underlying target organ damage from hypertension.
Related Links	https://bmcmedgenomics.biomedcentral.com/counter/pdf/10.1186/s12920-020-00791-0.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
ISSN	17558794
DOI	10.1186/s12920-020-00791-0
Journal	BMC Medical Genomics
Issue Number	1
Volume Number	13
Language	English
Publisher	BioMed Central
Publisher Date	2020-09-11
Access Restriction	Open
Subject Keyword	Human Genetics Microarrays Gene Expression Target organ damage DNA methylation Hypertension Estimated glomerular filtration rate Urinary albumin-creatinine ratio Left ventricular mass Relative wall thickness
Content Type	Text
Resource Type	Article
Subject	Genetics (clinical) Genetics
Journal Impact Factor	2.1/2023
5-Year Journal Impact Factor	2.5/2023

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