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Abstract
Twin and family studies have established the contribution of genetic factors to variation in metabolic, hematologic and immunological parameters. The majority of these studies analyzed single or combined traits into pre-defined syndromes. In the present study, we explore an alternative multivariate approach in which a broad range of metabolic, hematologic, and immunological traits are analyzed simultaneously to determine the resemblance of monozygotic (MZ) twin pairs, twin-spouse pairs and unrelated, non-cohabiting individuals. A total of 517 participants from the Netherlands Twin Register, including 210 MZ twin pairs and 64 twin-spouse pairs, took part in the study. Data were collected on body composition, blood pressure, heart rate, and multiple biomarkers assessed in fasting blood samples, including lipid levels, glucose, insulin, liver enzymes, hematological measurements and cytokine levels. For all 51 measured traits, pair-wise Pearson correlations, correcting for family relatedness, were calculated across all the individuals in the cohort. Hierarchical clustering techniques were applied to group the measured traits into sub-clusters based on similarity. Sub-clusters were observed among metabolic traits and among inflammatory markers. We defined a phenotypic profile as the collection of all the traits measured for a given individual. Average within-pair similarity of phenotypic profiles was determined for the groups of MZ twin pairs, spouse pairs and pairs of unrelated individuals. The average similarity across the full phenotypic profile was higher for MZ twin pairs than for spouse pairs, and lowest for pairs of unrelated individuals. Cohabiting MZ twins were more similar in their phenotypic profile compared to MZ twins who no longer lived together. The correspondence in the phenotypic profile is therefore determined to a large degree by familial, mostly genetic, factors, while household factors contribute to a lesser degree to profile similarity.
Highlights
Twin and family studies have been historically used to examine the effects of genetics and environment on a wide range of complex human phenotypic traits [1,2,3,4]
The metabolic syndrome has been characterized as consisting of several well established risk factors for cardiovascular disease, whose co-variation is largely due to genetic factors [13]
Many of the body composition measurements such as weight, waist, hip, waist to hip ratio were strongly correlated with blood pressure, cholesterol levels, insulin and glucose measurements and inversely correlated with HDL levels, defining the metabolic syndrome
Summary
Twin and family studies have been historically used to examine the effects of genetics and environment on a wide range of complex human phenotypic traits [1,2,3,4]. There has been an abundance of studies examining the influence of genetic factors on a large spectrum of cardiovascular, immunological and metabolic traits. Previous studies have shown genetic influences on indices of pro-inflammatory state, with heritability estimates ranging between 20 and 45% [11,12]. These measurements, are not independent from oneanother. The metabolic syndrome has been characterized as consisting of several well established risk factors for cardiovascular disease, whose co-variation is largely due to genetic factors [13]. The metabolic syndrome (obesity, hyperlipidemia, hyperglycemia and hypertension) is associated with many other traits that may explain cardiovascular disease, but are not formally part of the syndrome. Many studies that assess a large range of correlated biomarkers tend to analyze them in a one-by-one fashion, which fails to take into account their often-substantial inter-dependence
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