학술논문
Sex and statin-related genetic associations at the PCSK9 gene locus: results of genome-wide association meta-analysis
Document Type
article
Author
Janne Pott; Azin Kheirkhah; Jesper R. Gadin; Marcus E. Kleber; Graciela E. Delgado; Holger Kirsten; Lukas Forer; Stefanie M. Hauck; Ralph Burkhardt; Hubert Scharnagl; Markus Loeffler; Winfried März; Joachim Thiery; Christian Gieger; Annette Peters; Angela Silveira; Ferdinand van’t Hooft; Florian Kronenberg; Markus Scholz
Source
Biology of Sex Differences, Vol 15, Iss 1, Pp 1-18 (2024)
Subject
Language
English
ISSN
2042-6410
Abstract
Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key player of lipid metabolism with higher plasma levels in women throughout their life. Statin treatment affects PCSK9 levels also showing evidence of sex-differential effects. It remains unclear whether these differences can be explained by genetics. Methods We performed genome-wide association meta-analyses (GWAS) of PCSK9 levels stratified for sex and statin treatment in six independent studies of Europeans (8936 women/11,080 men respectively 14,825 statin-free/5191 statin-treated individuals). Loci associated in one of the strata were tested for statin- and sex-interactions considering all independent signals per locus. Independent variants at the PCSK9 gene locus were then used in a stratified Mendelian Randomization analysis (cis-MR) of PCSK9 effects on low-density lipoprotein cholesterol (LDL-C) levels to detect differences of causal effects between the subgroups. Results We identified 11 loci associated with PCSK9 in at least one stratified subgroup (p