Complex segregation analysis provides evidence for a major gene acting on serum triglyceride levels in 55 British families with familial combined hyperlipidemia.
- 1 August 1994
- journal article
- abstracts
- Published by Wolters Kluwer Health in Arteriosclerosis and Thrombosis: A Journal of Vascular Biology
- Vol. 14 (8), 1233-1249
- https://doi.org/10.1161/01.atv.14.8.1233
Abstract
Familial combined hyperlipidemia (FCHL) was first described as an autosomal dominant inherited trait with primary action on triglyceride levels and secondary effects on cholesterol metabolism. This conclusion has since been questioned by several groups despite subsequent supportive biochemical and metabolic studies. To reexplore the genetics of FCHL, we assembled 55 families from the United Kingdom comprising 559 persons ascertained through probands with both hypercholesterolemia and hypertriglyceridemia. The results of univariate complex segregation analysis were consistent with a major gene acting on triglyceride and explaining two thirds of the genetic variability and 20% of the phenotypic variance in triglyceride levels. Univariate analysis did not identify a major genetic component acting on cholesterol levels. Bivariate segregation analysis rejected a major gene model. We also reexamined the original FCHL pedigrees collected by Goldstein et al and obtained results similar to those in the UK families. The prospects for mapping putative major genes determining triglyceride levels in FCHL patients by linkage analysis are discussed.Keywords
This publication has 35 references indexed in Scilit:
- Genetic markers in the apo AI-CIII-AIV gene cluster for combined hyperlipidemia, hypertriglyceridemia, and predisposition to atherosclerosisAtherosclerosis, 1993
- Genetics of low-density lipoprotein subclassesCurrent Opinion in Lipidology, 1993
- Genetic basis of lipoprotein disorders.JCI Insight, 1989
- A mixed-model likelihood approximation on large pedigreesComputers and Biomedical Research, 1982
- Kinetic bases of the primar hperlipidaemias: studies of apolipoprotein B turnover in geneticall defined subjectsEuropean Journal of Clinical Investigation, 1980
- Probability functions on complex pedigreesAdvances in Applied Probability, 1978
- Segregation and linkage analyses of a large pedigree with hypertriglyceridemiaAmerican Journal of Medical Genetics, 1977
- A new look at the statistical model identificationIEEE Transactions on Automatic Control, 1974
- FAMILY STUDY OF SERUM LIPIDS AND LIPOPROTEINS IN CORONARY HEART-DISEASEThe Lancet, 1973
- Estimation of Parameters for a Mixture of Normal DistributionsTechnometrics, 1966