| Literature DB >> 32520614 |
Yisong Huang1, Miina Ollikainen2,3, Maheswary Muniandy2, Shaoyong Su1, James Wilson, Harold Snieder4, Jaakko Kaprio2,3, Xiaoling Wang1, Tao Zhang5, Jenny van Dongen6, Guang Hao1, Peter J van der Most4, Yue Pan1, Natalia Pervjakova7, Yan V Sun8, Qin Hui8, Jari Lahti9,10, Eliza Fraszczyk4, Xueling Lu4,11, Dianjianyi Sun12,13, Melissa A Richard14, Gonneke Willemsen6, Kauko Heikkila2, Irene Mateo Leach15, Nina Mononen16,17, Mika Kähönen18, Mikko A Hurme19, Olli T Raitakari20,21, Amanda J Drake22, Markus Perola23, Marja-Liisa Nuotio23, Yunfeng Huang8, Batbayar Khulan22, Katri Räikkönen10, Bruce H R Wolffenbuttel24, Alexandra Zhernakova25, Jingyuan Fu25,26, Haidong Zhu1, Yanbin Dong1, Jana V van Vliet-Ostaptchouk4,24,27, Lude Franke25, Johan G Eriksson28,29, Myriam Fornage30,31, Lili Milani7, Terho Lehtimäki16,17, Viola Vaccarino8, Dorret I Boomsma6, Pim van der Harst15,32, Eco J C de Geus6, Veikko Salomaa23, Shengxu Li33, Wei Chen12.
Abstract
We conducted an epigenome-wide association study meta-analysis on blood pressure (BP) in 4820 individuals of European and African ancestry aged 14 to 69. Genome-wide DNA methylation data from peripheral leukocytes were obtained using the Infinium Human Methylation 450k BeadChip. The epigenome-wide association study meta-analysis identified 39 BP-related CpG sites with P<1×10-5. In silico replication in the CHARGE consortium of 17 010 individuals validated 16 of these CpG sites. Out of the 16 CpG sites, 13 showed novel association with BP. Conversely, out of the 126 CpG sites identified as being associated (P<1×10-7) with BP in the CHARGE consortium, 21 were replicated in the current study. Methylation levels of all the 34 CpG sites that were cross-validated by the current study and the CHARGE consortium were heritable and 6 showed association with gene expression. Furthermore, 9 CpG sites also showed association with BP with P<0.05 and consistent direction of the effect in the meta-analysis of the Finnish Twin Cohort (199 twin pairs and 4 singletons; 61% monozygous) and the Netherlands Twin Register (266 twin pairs and 62 singletons; 84% monozygous). Bivariate quantitative genetic modeling of the twin data showed that a majority of the phenotypic correlations between methylation levels of these CpG sites and BP could be explained by shared unique environmental rather than genetic factors, with 100% of the correlations of systolic BP with cg19693031 (TXNIP) and cg00716257 (JDP2) determined by environmental effects acting on both systolic BP and methylation levels.Entities:
Keywords: DNA methylation; Twin study; blood pressure; epigenome; hypertension
Mesh：
Year: 2020 PMID： 32520614 PMCID： PMC7295009 DOI： 10.1161/HYPERTENSIONAHA.120.14973
Source DB: PubMed Journal: Hypertension ISSN： 0194-911X Impact factor: 10.190