Lipidome- and genome-wide study to understand sex differences in circulatory lipids

Abstract

Despite well-recognized difference in the atherosclerotic cardiovascular disease (ASCVD) risk between men and women, sex differences in risk factors and sex specific mechanisms in the pathophysiology of ASCVD remain poorly understood. Lipid metabolism plays a central role in the development of ASCVD. Understanding sex differences in lipids and their genetic determinants could provide mechanistic insights into sex differences in ASCVD and aid in precise risk assessment. Thus, we examined sex differences in plasma levels of 179 lipid species from 7,266 participants and performed sex-stratified genome-wide association studies (GWAS) to evaluate contribution of genetic factors in sex differences. We sought for replication using independent data from 2,045 participants. Significant sex differences in levels of 141 lipid species were observed (P<7.0×10−4). Interestingly, 121 lipid species showed significant age-sex interactions with opposite age-related changes in 39 lipid species. In general, most of the cholesteryl esters, ceramides, lysophospholipids and glycerides were higher in 45-50-year-old men compared with women of same age, but the sex-differences narrowed down or reversed with age. We did not observe any major differences in genetic effect in the sex stratified GWAS which suggests that common genetic variants do not have a major role in sex differences in lipidome. In conclusion, our study provides a comprehensive view of sex differences in circulatory lipids pointing to potential sex differences in lipid metabolism, highlighting need for sex- and age-specific prevention strategies.

The lipidomic correlates of epigenetic aging across the adult lifespan: A population‐based study

“…We found that lipid species, which were differently associated with AgeAccelPheno and AgeAccelGrim in men and women, predominately belonged to TAG and some phospholipid species (Figure S4), which is in line with reports from previous studies (Gonzalez-Covarrubias et al, 2013;Hoene et al, 2014;Tabassum et al, 2022).…”

Imputation of missing values in lipidomic datasets

“…The study protocols were approved by The Hospital District of Helsinki and Uusimaa Coordinating Ethics committees (approval No.∼281/13/03/00/14 (GeneRISK)). Mass spectrometry-based lipid analysis was performed for 7302 individuals from the GeneRISK cohort by shotgun lipidomic analysis at Lipotype GmbH (Dresden, Germany) [6,7].…”