Shared genetic variance between the features of the metabolic syndrome: heritability studies

Heritability estimates of MetS range from approximately 10%-30%. The genetic variation that is shared among MetS features can be calculated by genetic correlation coefficients. The objective of this paper is to identify MetS feature as well as MetS related features which have much genetic variation in common, by reviewing the literature regarding genetic correlation coefficients. Identification of features, that have much genetic variation in common, may eventually facilitate the search for pleitropic genetic variants that may explain the clustering of MetS features. A PubMed search with the search terms "(metabolic syndrome OR insulin resistance syndrome) and (heritability OR genetic correlation OR pleiotropy)" was performed. Studies published before 7th July 2011, which presented genetic correlation coefficients between the different MetS features and genetic correlation coefficients of MetS and its features with adipose tissue-, pro-inflammatory and pro-thrombotic biomarkers were included. Nine twin and 19 family studies were included in the review. Genetic correlations varied, but were strongest between waist circumference and HOMA-IR (r(2): 0.36 to 0.79, median: 0.50), HDL cholesterol and triglycerides (r(2): -0.05 to -0.59, median -0.45), adiponectin and MetS (r(2): -0.32 to -0.43; median -0.38), adiponectin and insulin (r(2): -0.10 to -0.60; median -0.30) and between adiponectin and HDL-cholesterol (r(2): -0.22 to -0.51, median -0.29). In conclusion, heritability studies suggest that genetic pleiotropy exist especially between certain MetS features, as well as between MetS and adiponectin. Further research on actual genetic variants responsible for the genetic pleiotropy of these combinations will provide more insight into the etiology of MetS.