Abstract
Metabolic syndrome is a complex human disorder characterized by a cluster of conditions (increased blood pressure, hyperglycemia, excessive body fat around the waist, and abnormal cholesterol or triglyceride levels). Any of these conditions increases the risk of serious disorders such as diabetes or cardiovascular disease. Currently, the degree of genetic regulation of this syndrome is under debate and partially unknown. The principal aim of this study was to estimate the genetic component and the common environmental effects in different populations using full pedigree and genomic information. We used three large populations (Gubbio, ARIC, and Ogliastra cohorts) to estimate the heritability of metabolic syndrome. Due to both pedigree and genotyped data, different approaches were applied to summarize relatedness conditions. Linear mixed models (LLM) using average information restricted maximum likelihood (AIREML) algorithm were applied to partition the variances and estimate heritability (h2) and common sib–household effect (c2). Globally, results obtained from pedigree information showed a significant heritability (h2: 0.286 and 0.271 in Gubbio and Ogliastra, respectively), whereas a lower, but still significant heritability was found using SNPs data (\(h_{\text{SNP}}^{2}\): 0.167 and 0.254 in ARIC and Ogliastra). The remaining heritability between h2 and \(h_{\text{SNP}}^{2}\) ranged between 0.031 and 0.237. Finally, the common environmental c2 in Gubbio and Ogliastra were also significant accounting for about 11% of the phenotypic variance. Availability of different kinds of populations and data helped us to better understand what happened when heritability of metabolic syndrome is estimated and account for different possible confounding. Furthermore, the opportunity of comparing different results provided more precise and less biased estimation of heritability.
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Acknowledgements
The authors thank the staff and participants of the ARIC, Gubbio, and Ogliastra studies for their important contributions. The ARIC study was carried out as a collaborative study supported by the National Heart, Lung, and Blood Institute contracts (HHSN26820 1100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN26820 1100010C, HHSN268201100011C, and HHSN268201100012C). The Gubbio study was originally funded by Merck Sharp and Dohme, Italy, and the Department of Outcome Research of Merck & Co Inc., USA. Funds were also obtained from Grant # R01HL40397 – 02 of the National Heart Lung and Blood Institute, Bethesda, Maryland, USA, and Ministero Italiano di Università e Ricerca (Grant # 068034, PRIN 2004). The present analyses were done in the context of the Istituto Auxologico Italiano participation to EU MASCARA project/EC-7th Framework Program contract no. 278249. The Ogliastra study was supported by a grant from the Italian Ministry of Education, University and Research: MERIT RBNE08NKH7_007.
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Graziano, F., Biino, G., Bonati, M.T. et al. Estimation of metabolic syndrome heritability in three large populations including full pedigree and genomic information. Hum Genet 138, 739–748 (2019). https://doi.org/10.1007/s00439-019-02024-6
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DOI: https://doi.org/10.1007/s00439-019-02024-6