Sex-Specific Parental Effects on Offspring Lipid Levels

Irene M. Predazzi, Rafal S. Sobota, Serena Sanna, William S. Bush, Jacquelaine Bartlett, Jessica S. Lilley, MacRae F. Linton, David Schlessinger, Francesco Cucca, Sergio Fazio, Scott M. Williams

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

BACKGROUND: Plasma lipid levels are highly heritable traits, but known genetic loci can only explain a small portion of their heritability.

METHODS AND RESULTS: In this study, we analyzed the role of parental levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs) in explaining the values of the corresponding traits in adult offspring. We also evaluated the contribution of nongenetic factors that influence lipid traits (age, body mass index, smoking, medications, and menopause) alone and in combination with variability at the genetic loci known to associate with TC, LDL-C, HDL-C, and TG levels. We performed comparisons among different sex-specific regression models in 416 families from the Framingham Heart Study and 304 from the SardiNIA cohort. Models including parental lipid levels explain significantly more of the trait variation than models without these measures, explaining up to ≈39% of the total trait variation. Of this variation, the parent-of-origin effect explains as much as ≈15% and it does so in a sex-specific way. This observation is not owing to shared environment, given that spouse-pair correlations were negligible (<1.5% explained variation in all cases) and is distinct from previous genetic and acquired factors that are known to influence serum lipid levels.

CONCLUSIONS: These findings support the concept that unknown genetic and epigenetic contributors are responsible for most of the heritable component of the plasma lipid phenotype, and that, at present, the clinical utility of knowing age-matched parental lipid levels in assessing risk of dyslipidemia supersedes individual locus effects. Our results support the clinical utility of knowing parental lipid levels in assessing future risk of dyslipidemia.

Original languageEnglish (US)
JournalJournal of the American Heart Association
Volume4
Issue number7
DOIs
StatePublished - Jun 30 2015
Externally publishedYes

Fingerprint

Lipids
Genetic Loci
Dyslipidemias
LDL Cholesterol
HDL Cholesterol
Cholesterol
Genetic Phenomena
Adult Children
Menopause
Spouses
Epigenomics
Italy
Body Mass Index
Parents
Smoking
Phenotype
Serum
lipoprotein triglyceride

Keywords

  • cholesterol
  • genetics
  • lipids
  • risk factors
  • sex

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Predazzi, I. M., Sobota, R. S., Sanna, S., Bush, W. S., Bartlett, J., Lilley, J. S., ... Williams, S. M. (2015). Sex-Specific Parental Effects on Offspring Lipid Levels. Journal of the American Heart Association, 4(7). https://doi.org/10.1161/JAHA.115.001951

Sex-Specific Parental Effects on Offspring Lipid Levels. / Predazzi, Irene M.; Sobota, Rafal S.; Sanna, Serena; Bush, William S.; Bartlett, Jacquelaine; Lilley, Jessica S.; Linton, MacRae F.; Schlessinger, David; Cucca, Francesco; Fazio, Sergio; Williams, Scott M.

In: Journal of the American Heart Association, Vol. 4, No. 7, 30.06.2015.

Research output: Contribution to journalArticle

Predazzi, IM, Sobota, RS, Sanna, S, Bush, WS, Bartlett, J, Lilley, JS, Linton, MF, Schlessinger, D, Cucca, F, Fazio, S & Williams, SM 2015, 'Sex-Specific Parental Effects on Offspring Lipid Levels', Journal of the American Heart Association, vol. 4, no. 7. https://doi.org/10.1161/JAHA.115.001951
Predazzi IM, Sobota RS, Sanna S, Bush WS, Bartlett J, Lilley JS et al. Sex-Specific Parental Effects on Offspring Lipid Levels. Journal of the American Heart Association. 2015 Jun 30;4(7). https://doi.org/10.1161/JAHA.115.001951
Predazzi, Irene M. ; Sobota, Rafal S. ; Sanna, Serena ; Bush, William S. ; Bartlett, Jacquelaine ; Lilley, Jessica S. ; Linton, MacRae F. ; Schlessinger, David ; Cucca, Francesco ; Fazio, Sergio ; Williams, Scott M. / Sex-Specific Parental Effects on Offspring Lipid Levels. In: Journal of the American Heart Association. 2015 ; Vol. 4, No. 7.
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abstract = "BACKGROUND: Plasma lipid levels are highly heritable traits, but known genetic loci can only explain a small portion of their heritability.METHODS AND RESULTS: In this study, we analyzed the role of parental levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs) in explaining the values of the corresponding traits in adult offspring. We also evaluated the contribution of nongenetic factors that influence lipid traits (age, body mass index, smoking, medications, and menopause) alone and in combination with variability at the genetic loci known to associate with TC, LDL-C, HDL-C, and TG levels. We performed comparisons among different sex-specific regression models in 416 families from the Framingham Heart Study and 304 from the SardiNIA cohort. Models including parental lipid levels explain significantly more of the trait variation than models without these measures, explaining up to ≈39{\%} of the total trait variation. Of this variation, the parent-of-origin effect explains as much as ≈15{\%} and it does so in a sex-specific way. This observation is not owing to shared environment, given that spouse-pair correlations were negligible (<1.5{\%} explained variation in all cases) and is distinct from previous genetic and acquired factors that are known to influence serum lipid levels.CONCLUSIONS: These findings support the concept that unknown genetic and epigenetic contributors are responsible for most of the heritable component of the plasma lipid phenotype, and that, at present, the clinical utility of knowing age-matched parental lipid levels in assessing risk of dyslipidemia supersedes individual locus effects. Our results support the clinical utility of knowing parental lipid levels in assessing future risk of dyslipidemia.",
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N2 - BACKGROUND: Plasma lipid levels are highly heritable traits, but known genetic loci can only explain a small portion of their heritability.METHODS AND RESULTS: In this study, we analyzed the role of parental levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs) in explaining the values of the corresponding traits in adult offspring. We also evaluated the contribution of nongenetic factors that influence lipid traits (age, body mass index, smoking, medications, and menopause) alone and in combination with variability at the genetic loci known to associate with TC, LDL-C, HDL-C, and TG levels. We performed comparisons among different sex-specific regression models in 416 families from the Framingham Heart Study and 304 from the SardiNIA cohort. Models including parental lipid levels explain significantly more of the trait variation than models without these measures, explaining up to ≈39% of the total trait variation. Of this variation, the parent-of-origin effect explains as much as ≈15% and it does so in a sex-specific way. This observation is not owing to shared environment, given that spouse-pair correlations were negligible (<1.5% explained variation in all cases) and is distinct from previous genetic and acquired factors that are known to influence serum lipid levels.CONCLUSIONS: These findings support the concept that unknown genetic and epigenetic contributors are responsible for most of the heritable component of the plasma lipid phenotype, and that, at present, the clinical utility of knowing age-matched parental lipid levels in assessing risk of dyslipidemia supersedes individual locus effects. Our results support the clinical utility of knowing parental lipid levels in assessing future risk of dyslipidemia.

AB - BACKGROUND: Plasma lipid levels are highly heritable traits, but known genetic loci can only explain a small portion of their heritability.METHODS AND RESULTS: In this study, we analyzed the role of parental levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs) in explaining the values of the corresponding traits in adult offspring. We also evaluated the contribution of nongenetic factors that influence lipid traits (age, body mass index, smoking, medications, and menopause) alone and in combination with variability at the genetic loci known to associate with TC, LDL-C, HDL-C, and TG levels. We performed comparisons among different sex-specific regression models in 416 families from the Framingham Heart Study and 304 from the SardiNIA cohort. Models including parental lipid levels explain significantly more of the trait variation than models without these measures, explaining up to ≈39% of the total trait variation. Of this variation, the parent-of-origin effect explains as much as ≈15% and it does so in a sex-specific way. This observation is not owing to shared environment, given that spouse-pair correlations were negligible (<1.5% explained variation in all cases) and is distinct from previous genetic and acquired factors that are known to influence serum lipid levels.CONCLUSIONS: These findings support the concept that unknown genetic and epigenetic contributors are responsible for most of the heritable component of the plasma lipid phenotype, and that, at present, the clinical utility of knowing age-matched parental lipid levels in assessing risk of dyslipidemia supersedes individual locus effects. Our results support the clinical utility of knowing parental lipid levels in assessing future risk of dyslipidemia.

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