title: Genetic effects on variation in red-blood-cell folate in adults: implications for the familial aggregation of neural tube defects.
abstract: Recent studies have implicated folic acid as an important determinant of normal human growth, development, and function. Insufficient folate levels appear to be a risk factor for neural tube defects (NTD), as well as for several chronic diseases of adulthood. However, relatively little is known about the factors that influence folate status in the general population. To estimate the relative contribution of genetic and nongenetic factors to variation in folate, we have evaluated red blood cell (RBC) folate levels in 440 pairs of MZ twins and in 331 pairs of DZ twins. The data were best described by a model in which 46% of the variance in RBC folate was attributable to additive genetic effects, 16% of the variance was due to measured phenotypic covariates, and 38% of the variance was due to random environmental effects. Moreover, the correlations for RBC folate in MZ co-twins (r = .46) and in repeat measures from the same individual (r = .51) were very similar, indicating that virtually all repeatable variation in RBC folate is attributable to genetic factors. On the basis of these results, it would seem reasonable to initiate a search for the specific genes that influence RBC folate levels in the general population. Such genes ultimately may be used to identify individuals at increased risk for NTD and other folate-related diseases.
authors.affiliation: Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia, PA 19104, USA. lauramit@mail.med.upenn.edu
authors.forename: L E
authors.initials: LE
authors.lastname: Mitchell
authors.forename: D L
authors.initials: DL
authors.lastname: Duffy
authors.forename: P
authors.initials: P
authors.lastname: Duffy
authors.forename: G
authors.initials: G
authors.lastname: Bellingham
authors.forename: N G
authors.initials: NG
authors.lastname: Martin
mesh_terms: D000328:Adult; D000367:Age Factors; D001800:Blood Specimen Collection; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D005492:Folic Acid / Q000097:blood*; D020022:Genetic Predisposition to Disease; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D008957:Models, Genetic; D015233:Models, Statistical; D009436:Neural Tube Defects / Q000235:genetics*; D016017:Odds Ratio; D012307:Risk Factors; D012727:Sex Characteristics; D018709:Statistics, Nonparametric; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic
chemical_list: D005492:Folic Acid