Genetic and environmental correlational structure among metabolic syndrome endophenotypes

Stacey S. Cherny, Frances M.K. Williams, Gregory Livshits*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Abstract: Metabolic syndrome (MetS) is diagnosed by the presence of high scores on three or more metabolic traits, including systolic and diastolic blood pressure (SBP, DBP), glucose and insulin levels, cholesterol and triglyceride (TG) levels, and central obesity. A diagnosis of MetS is associated with increased risk of cardiovascular disease and type 2 diabetes. The components of MetS have long been demonstrated to have substantial genetic components, but their genetic overlap is less well understood. The present paper takes a multi-prong approach to examining the extent of this genetic overlap. This includes the quantitative genetic and additive Bayesian network modeling of the large TwinsUK project and examination of the results of genome-wide association study (GWAS) of UK Biobank data through use of LD score regression and examination of the number of genes and pathways identified in the GWASes which overlap across MetS traits. Results demonstrate a modest genetic overlap, and the genetic correlations obtained from TwinsUK and UK Biobank are nearly identical. However, these correlations imply more genetic dissimilarity than similarity. Furthermore, examination of the extent of overlap in significant GWAS hits, both at the gene and pathway level, again demonstrates only modest but significant genetic overlap. This lends support to the idea that in clinical treatment of MetS, treating each of the components individually may be an important way to address MetS.

Original languageEnglish
Pages (from-to)225-236
Number of pages12
JournalAnnals of Human Genetics
Issue number5
StatePublished - Sep 2022


FundersFunder number
Wellcome Trust
Manchester Biomedical Research Centre
National Institute for Health Research
King's College London
Israel Science Foundation2054/19
Guy's and St Thomas' NHS Foundation Trust
Seventh Framework ProgrammeFP7/2007‐2013


    • HDL
    • cholesterol
    • glucose
    • human genetics
    • metabolic syndrome
    • triglycerides


    Dive into the research topics of 'Genetic and environmental correlational structure among metabolic syndrome endophenotypes'. Together they form a unique fingerprint.

    Cite this