title: Sex-Specific Parental Effects on Offspring Lipid Levels.
abstract: BACKGROUND
  Plasma lipid levels are highly heritable traits, but known genetic loci can only explain a small portion of their heritability.
  
  
  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.
authors.affiliation: Atherosclerosis Research Unit, Departments of Medicine and Pharmacology, Vanderbilt University Medical Center, Nashville, TN (I.M.P., J.S.L., M.R.F.L., S.F.) Knight Cardiovascular Institute, Center for Preventive Cardiology, Oregon Health and Science University, Portland, OR (I.M.P., S.F.).
authors.forename: Irene M
authors.initials: IM
authors.lastname: Predazzi
authors.affiliation: Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN (R.S.S., W.S.B.) Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, NH (R.S.S., J.B., S.M.W.).
authors.forename: Rafal S
authors.initials: RS
authors.lastname: Sobota
authors.affiliation: Istituto di Ricerca Genetica e Biomedica (IRGB), CNR, Monserrato, Italy (S.S., F.C.).
authors.forename: Serena
authors.initials: S
authors.lastname: Sanna
authors.affiliation: Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN (R.S.S., W.S.B.) Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH (W.S.B.).
authors.forename: William S
authors.initials: WS
authors.lastname: Bush
authors.affiliation: Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, NH (R.S.S., J.B., S.M.W.).
authors.forename: Jacquelaine
authors.initials: J
authors.lastname: Bartlett
authors.affiliation: Atherosclerosis Research Unit, Departments of Medicine and Pharmacology, Vanderbilt University Medical Center, Nashville, TN (I.M.P., J.S.L., M.R.F.L., S.F.) Division of Endocrinology, Department of Pediatrics, University of Mississippi School of Medicine, Jackson, MS (J.S.L.).
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Lilley
authors.affiliation: Atherosclerosis Research Unit, Departments of Medicine and Pharmacology, Vanderbilt University Medical Center, Nashville, TN (I.M.P., J.S.L., M.R.F.L., S.F.).
authors.forename: MacRae F
authors.initials: MF
authors.lastname: Linton
authors.affiliation: Laboratory of Genetics, NIA, Baltimore, MD (D.S.).
authors.forename: David
authors.initials: D
authors.lastname: Schlessinger
authors.affiliation: Istituto di Ricerca Genetica e Biomedica (IRGB), CNR, Monserrato, Italy (S.S., F.C.).
authors.forename: Francesco
authors.initials: F
authors.lastname: Cucca
authors.affiliation: Atherosclerosis Research Unit, Departments of Medicine and Pharmacology, Vanderbilt University Medical Center, Nashville, TN (I.M.P., J.S.L., M.R.F.L., S.F.) Knight Cardiovascular Institute, Center for Preventive Cardiology, Oregon Health and Science University, Portland, OR (I.M.P., S.F.).
authors.forename: Sergio
authors.initials: S
authors.lastname: Fazio
authors.affiliation: Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, NH (R.S.S., J.B., S.M.W.).
authors.forename: Scott M
authors.initials: SM
authors.lastname: Williams
mesh_terms: D000328:Adult; D032721:Adult Children; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D050171:Dyslipidemias / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005220:Fathers; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D007558:Italy / Q000453:epidemiology; D050356:Lipid Metabolism / Q000235:genetics*; D008055:Lipids / Q000097:blood*; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D008954:Models, Biological; D009035:Mothers; D010375:Pedigree; D010641:Phenotype; D012307:Risk Factors; D012737:Sex Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids; D014280:Triglycerides; D002784:Cholesterol
keywords: cholesterol; genetics; lipids; risk factors; sex