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Effect of genome and environment on metabolic and inflammatory profiles.

Sirota M, Willemsen G, Sundar P, Pitts SJ, Potluri S, Prifti E, Kennedy S, Ehrlich SD, Neuteboom J, Kluft C, Malone KE, Cox DR, de Geus EJ, Boomsma DI - PLoS ONE (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Rinat-Pfizer, South San Francisco, California, United States of America.

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.

No MeSH data available.


Study overview and participant characterization.A) Study Design. Pairs of twins were recruited for this study. A proportion of the cohort consists of twins who are co-habiting. Spouses were also recruited to index resemblance through shared household factors; B) Age distribution in twin study participants stratified by co-habitation status; C) Age distribution in study participants stratified by sex.
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pone.0120898.g001: Study overview and participant characterization.A) Study Design. Pairs of twins were recruited for this study. A proportion of the cohort consists of twins who are co-habiting. Spouses were also recruited to index resemblance through shared household factors; B) Age distribution in twin study participants stratified by co-habitation status; C) Age distribution in study participants stratified by sex.

Mentions: In addition to studying relationships between the traits, we examine the similarity of specific phenotypic traits as well as phenotypic profiles across individuals. The inclusion of spouses, who share a household, in addition to MZ twin pairs, who share their genome, allow for an exploration of genetic and environmental influences on the phenotypic profile by determining the similarity in profile for MZ pairs, twin-spouse pairs and unrelated individuals (who share neither genes nor environment). Family members may resemble one-another due to shared genes and shared environments. In the classical twin design the similarity in MZ and DZ twins is compared to disentangle the effect of these genetic and the shared environmental influences. Here, we use an alternative method by contrasting MZ twin similarity to the similarity in spouse pairs, who share a household but can be considered not to share a genetic background [18]. A higher profile similarity in MZ twins compared to unrelated individuals indicates familial, genetic and/or shared—childhood- environment influences (Fig. 1A). A staircase pattern with similarity being highest in MZ twins, lower in spouses, and much lower among unrelated individuals, would indicate influence of shared environment, where spouse resemblance provides an upper limit for household effects if phenotypic assortative mating is also present. In contrast, a pattern in which the similarity for spouses is comparable to unrelated individuals, with MZ twin similarity being higher, would indicate that household effects do not play a role. The importance of sharing a household is further explored by determining profile similarity in MZ twins who cohabit and in MZ twins who live separate from each other. If non-cohabiting twins are less alike in their profile than cohabiting twins, this points to an influence of shared household factors, although we recognize that cohabiting twins tend to be younger.


Effect of genome and environment on metabolic and inflammatory profiles.

Sirota M, Willemsen G, Sundar P, Pitts SJ, Potluri S, Prifti E, Kennedy S, Ehrlich SD, Neuteboom J, Kluft C, Malone KE, Cox DR, de Geus EJ, Boomsma DI - PLoS ONE (2015)

Study overview and participant characterization.A) Study Design. Pairs of twins were recruited for this study. A proportion of the cohort consists of twins who are co-habiting. Spouses were also recruited to index resemblance through shared household factors; B) Age distribution in twin study participants stratified by co-habitation status; C) Age distribution in study participants stratified by sex.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390246&req=5

pone.0120898.g001: Study overview and participant characterization.A) Study Design. Pairs of twins were recruited for this study. A proportion of the cohort consists of twins who are co-habiting. Spouses were also recruited to index resemblance through shared household factors; B) Age distribution in twin study participants stratified by co-habitation status; C) Age distribution in study participants stratified by sex.
Mentions: In addition to studying relationships between the traits, we examine the similarity of specific phenotypic traits as well as phenotypic profiles across individuals. The inclusion of spouses, who share a household, in addition to MZ twin pairs, who share their genome, allow for an exploration of genetic and environmental influences on the phenotypic profile by determining the similarity in profile for MZ pairs, twin-spouse pairs and unrelated individuals (who share neither genes nor environment). Family members may resemble one-another due to shared genes and shared environments. In the classical twin design the similarity in MZ and DZ twins is compared to disentangle the effect of these genetic and the shared environmental influences. Here, we use an alternative method by contrasting MZ twin similarity to the similarity in spouse pairs, who share a household but can be considered not to share a genetic background [18]. A higher profile similarity in MZ twins compared to unrelated individuals indicates familial, genetic and/or shared—childhood- environment influences (Fig. 1A). A staircase pattern with similarity being highest in MZ twins, lower in spouses, and much lower among unrelated individuals, would indicate influence of shared environment, where spouse resemblance provides an upper limit for household effects if phenotypic assortative mating is also present. In contrast, a pattern in which the similarity for spouses is comparable to unrelated individuals, with MZ twin similarity being higher, would indicate that household effects do not play a role. The importance of sharing a household is further explored by determining profile similarity in MZ twins who cohabit and in MZ twins who live separate from each other. If non-cohabiting twins are less alike in their profile than cohabiting twins, this points to an influence of shared household factors, although we recognize that cohabiting twins tend to be younger.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Rinat-Pfizer, South San Francisco, California, United States of America.

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.

No MeSH data available.