Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1997 Jun;60(6):1502–1512. doi: 10.1086/515462

Heritability of longitudinal changes in coronary-heart-disease risk factors in women twins.

Y Friedlander 1, M A Austin 1, B Newman 1, K Edwards 1, E I Mayer-Davis 1, M C King 1
PMCID: PMC1716110  PMID: 9199573

Abstract

Numerous studies have demonstrated genetic influences on levels of coronary heart disease (CHD) risk factors, but there also may be genetic effects on the intraindividual variation in these risk factors over time. Changes in risk factors are likely to reflect genetic-environmental interactions and may have important implications for understanding CHD risk. The present study examines the heritability of changes in CHD risk factors, using data from the two examinations by the Kaiser Permanente Women Twins Study, performed a decade apart. The sample consisted of 348 pairs of women twins who participated in both examinations, including 203 MZ pairs and 145 DZ pairs. Average ages at the two examinations were 41 and 51 years, respectively. By means of three different statistical analytic approaches, moderate heritability estimates were demonstrated for changes in LDL cholesterol (h2 = .25-.36) and in HDL cholesterol (h2 = .23-.58), some of which were statistically significant. Although small to moderate heritability estimates were found for systolic blood pressure (.18-.37; P < .05 for some estimates), no genetic influence on changes in diastolic blood pressure was detected. Based on longitudinal twin data in women, this study demonstrates a genetic influence on changes in both lipoprotein risk factors and systolic blood pressure over a decade. In addition to environmental factors, which clearly are operating, the effect of various "variability genes" may be acting independently of the genetic influences on the absolute levels of these risk factors. Both mapping the gene(s) underlying intraindividual variations in these CHD risk factors and understanding their function(s) could lead to targeted intervention strategies to reduce CHD risk among genetically susceptible individuals.

Full text

PDF
1504

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Annest J. L., Sing C. F., Biron P., Mongeau J. G. Familial aggregation of blood pressure and weight in adoptive families. II. Estimation of the relative contributions of genetic and common environmental factors to blood pressure correlations between family members. Am J Epidemiol. 1979 Oct;110(4):492–503. doi: 10.1093/oxfordjournals.aje.a112830. [DOI] [PubMed] [Google Scholar]
  2. Austin M. A., King M. C., Bawol R. D., Hulley S. B., Friedman G. D. Risk factors for coronary heart disease in adult female twins. Genetic heritability and shared environmental influences. Am J Epidemiol. 1987 Feb;125(2):308–318. doi: 10.1093/oxfordjournals.aje.a114531. [DOI] [PubMed] [Google Scholar]
  3. Austin M. A., Newman B. Genetic influence on smoking. N Engl J Med. 1993 Feb 4;328(5):353–354. doi: 10.1056/NEJM199302043280514. [DOI] [PubMed] [Google Scholar]
  4. Austin M. A., Sandholzer C., Selby J. V., Newman B., Krauss R. M., Utermann G. Lipoprotein(a) in women twins: heritability and relationship to apolipoprotein(a) phenotypes. Am J Hum Genet. 1992 Oct;51(4):829–840. [PMC free article] [PubMed] [Google Scholar]
  5. Berg K., Kondo I., Drayna D., Lawn R. "Variability gene" effect of cholesteryl ester transfer protein (CETP) genes. Clin Genet. 1989 Jun;35(6):437–445. doi: 10.1111/j.1399-0004.1989.tb02969.x. [DOI] [PubMed] [Google Scholar]
  6. Berg K. Variability gene effect on cholesterol at the Kidd blood group locus. Clin Genet. 1988 Feb;33(2):102–107. doi: 10.1111/j.1399-0004.1988.tb03419.x. [DOI] [PubMed] [Google Scholar]
  7. Blangero J., MacCluer J. W., Kammerer C. M., Mott G. E., Dyer T. D., McGill H. C., Jr Genetic analysis of apolipoprotein A-I in two dietary environments. Am J Hum Genet. 1990 Sep;47(3):414–428. [PMC free article] [PubMed] [Google Scholar]
  8. Boerwinkle E., Visvikis S., Welsh D., Steinmetz J., Hanash S. M., Sing C. F. The use of measured genotype information in the analysis of quantitative phenotypes in man. II. The role of the apolipoprotein E polymorphism in determining levels, variability, and covariability of cholesterol, betalipoprotein, and triglycerides in a sample of unrelated individuals. Am J Med Genet. 1987 Jul;27(3):567–582. doi: 10.1002/ajmg.1320270310. [DOI] [PubMed] [Google Scholar]
  9. Borecki I. B., Bonney G. E., Rice T., Bouchard C., Rao D. C. Influence of genotype-dependent effects of covariates on the outcome of segregation analysis of the body mass index. Am J Hum Genet. 1993 Sep;53(3):676–687. [PMC free article] [PubMed] [Google Scholar]
  10. Carmelli D., Selby J. V., Quiroga J., Reed T., Fabsitz R. R., Christian J. C. 16-year incidence of ischemic heart disease in the NHLBI twin study. A classification of subjects into high- and low-risk groups. Ann Epidemiol. 1994 May;4(3):198–204. doi: 10.1016/1047-2797(94)90097-3. [DOI] [PubMed] [Google Scholar]
  11. Cheng L. S., Carmelli D., Hunt S. C., Williams R. R. Evidence for a major gene influencing 7-year increases in diastolic blood pressure with age. Am J Hum Genet. 1995 Nov;57(5):1169–1177. [PMC free article] [PubMed] [Google Scholar]
  12. Christian J. C., Borhani N. O., Castelli W. P., Fabsitz R., Norton J. A., Jr, Reed T., Rosenman R., Wood P. D., Yu P. L. Plasma cholesterol variation in the National Heart, Lung and Blood Institute Twin Study. Genet Epidemiol. 1987;4(6):433–446. doi: 10.1002/gepi.1370040605. [DOI] [PubMed] [Google Scholar]
  13. Christian J. C., Carmelli D., Castelli W. P., Fabsitz R., Grim C. E., Meaney F. J., Norton J. A., Jr, Reed T., Williams C. J., Wood P. D. High density lipoprotein cholesterol. A 16-year longitudinal study in aging male twins. Arteriosclerosis. 1990 Nov-Dec;10(6):1020–1025. doi: 10.1161/01.atv.10.6.1020. [DOI] [PubMed] [Google Scholar]
  14. Christian J. C., Kang K. W., Norton J. J., Jr Choice of an estimate of genetic variance from twin data. Am J Hum Genet. 1974 Mar;26(2):154–161. [PMC free article] [PubMed] [Google Scholar]
  15. Christian J. C., Norton J. A., Jr, Sorbel J., Williams C. J. Comparison of analysis of variance and maximum likelihood based path analysis of twin data: partitioning genetic and environmental sources of covariance. Genet Epidemiol. 1995;12(1):27–35. doi: 10.1002/gepi.1370120104. [DOI] [PubMed] [Google Scholar]
  16. Colletto G. M., Cardon L. R., Fulker D. W. A genetic and environmental time series analysis of blood pressure in male twins. Genet Epidemiol. 1993;10(6):533–538. doi: 10.1002/gepi.1370100634. [DOI] [PubMed] [Google Scholar]
  17. Demant T., Bedford D., Packard C. J., Shepherd J. Influence of apolipoprotein E polymorphism on apolipoprotein B-100 metabolism in normolipemic subjects. J Clin Invest. 1991 Nov;88(5):1490–1501. doi: 10.1172/JCI115459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Demant T., Houlston R. S., Caslake M. J., Series J. J., Shepherd J., Packard C. J., Humphries S. E. Catabolic rate of low density lipoprotein is influenced by variation in the apolipoprotein B gene. J Clin Invest. 1988 Sep;82(3):797–802. doi: 10.1172/JCI113681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Edwards K. L., Austin M. A., Newman B., Mayer E., Krauss R. M., Selby J. V. Multivariate analysis of the insulin resistance syndrome in women. Arterioscler Thromb. 1994 Dec;14(12):1940–1945. doi: 10.1161/01.atv.14.12.1940. [DOI] [PubMed] [Google Scholar]
  20. Feinleib M., Garrison R. J., Fabsitz R., Christian J. C., Hrubec Z., Borhani N. O., Kannel W. B., Rosenman R., Schwartz J. T., Wagner J. O. The NHLBI twin study of cardiovascular disease risk factors: methodology and summary of results. Am J Epidemiol. 1977 Oct;106(4):284–285. doi: 10.1093/oxfordjournals.aje.a112464. [DOI] [PubMed] [Google Scholar]
  21. Friedlander Y., Berry E. M., Eisenberg S., Stein Y., Leitersdorf E. Plasma lipids and lipoproteins response to a dietary challenge: analysis of four candidate genes. Clin Genet. 1995 Jan;47(1):1–12. doi: 10.1111/j.1399-0004.1995.tb03913.x. [DOI] [PubMed] [Google Scholar]
  22. Friedlander Y., Elkana Y., Sinnreich R., Kark J. D. Genetic and environmental sources of fibrinogen variability in Israeli families: the Kibbutzim Family Study. Am J Hum Genet. 1995 May;56(5):1194–1206. [PMC free article] [PubMed] [Google Scholar]
  23. GROOVER M. E., Jr, JERNIGAN J. A., MARTIN C. D. Variations in serum lipid concentration and clinical coronary disease. Am J Med Sci. 1960 Feb;239:133–139. doi: 10.1097/00000441-196002000-00001. [DOI] [PubMed] [Google Scholar]
  24. Gaddi A., Ciarrocchi A., Matteucci A., Rimondi S., Ravaglia G., Descovich G. C., Sirtori C. R. Dietary treatment for familial hypercholesterolemia--differential effects of dietary soy protein according to the apolipoprotein E phenotypes. Am J Clin Nutr. 1991 May;53(5):1191–1196. doi: 10.1093/ajcn/53.5.1191. [DOI] [PubMed] [Google Scholar]
  25. Gylling H., Aalto-Setälä K., Kontula K., Miettinen T. A. Serum low density lipoprotein cholesterol level and cholesterol absorption efficiency are influenced by apolipoprotein B and E polymorphism and by the FH-Helsinki mutation of the low density lipoprotein receptor gene in familial hypercholesterolemia. Arterioscler Thromb. 1991 Sep-Oct;11(5):1368–1375. doi: 10.1161/01.atv.11.5.1368. [DOI] [PubMed] [Google Scholar]
  26. Hamm P., Shekelle R. B., Stamler J. Large fluctuations in body weight during young adulthood and twenty-five-year risk of coronary death in men. Am J Epidemiol. 1989 Feb;129(2):312–318. doi: 10.1093/oxfordjournals.aje.a115135. [DOI] [PubMed] [Google Scholar]
  27. Haviland M. B., Lussier-Cacan S., Davignon J., Sing C. F. Impact of apolipoprotein E genotype variation on means, variances, and correlations of plasma lipid, lipoprotein, and apolipoprotein traits in octogenarians. Am J Med Genet. 1995 Sep 25;58(4):315–331. doi: 10.1002/ajmg.1320580405. [DOI] [PubMed] [Google Scholar]
  28. Heath A. C., Neale M. C., Hewitt J. K., Eaves L. J., Fulker D. W. Testing structural equation models for twin data using LISREL. Behav Genet. 1989 Jan;19(1):9–35. doi: 10.1007/BF01065881. [DOI] [PubMed] [Google Scholar]
  29. Heller D. A., de Faire U., Pedersen N. L., Dahlén G., McClearn G. E. Genetic and environmental influences on serum lipid levels in twins. N Engl J Med. 1993 Apr 22;328(16):1150–1156. doi: 10.1056/NEJM199304223281603. [DOI] [PubMed] [Google Scholar]
  30. Hong Y., de Faire U., Heller D. A., McClearn G. E., Pedersen N. Genetic and environmental influences on blood pressure in elderly twins. Hypertension. 1994 Dec;24(6):663–670. doi: 10.1161/01.hyp.24.6.663. [DOI] [PubMed] [Google Scholar]
  31. Houlston R. S., Turner P. R., Revill J., Lewis B., Humphries S. E. The fractional catabolic rate of low density lipoprotein in normal individuals is influenced by variation in the apolipoprotein B gene: a preliminary study. Atherosclerosis. 1988 May;71(1):81–85. doi: 10.1016/0021-9150(88)90305-x. [DOI] [PubMed] [Google Scholar]
  32. Hunt S. C., Hasstedt S. J., Kuida H., Stults B. M., Hopkins P. N., Williams R. R. Genetic heritability and common environmental components of resting and stressed blood pressures, lipids, and body mass index in Utah pedigrees and twins. Am J Epidemiol. 1989 Mar;129(3):625–638. doi: 10.1093/oxfordjournals.aje.a115175. [DOI] [PubMed] [Google Scholar]
  33. Hwa J. J., Zollman S., Warden C. H., Taylor B. A., Edwards P. A., Fogelman A. M., Lusis A. J. Genetic and dietary interactions in the regulation of HMG-CoA reductase gene expression. J Lipid Res. 1992 May;33(5):711–725. [PubMed] [Google Scholar]
  34. Kirk E. A., Moe G. L., Caldwell M. T., Lernmark J. A., Wilson D. L., LeBoeuf R. C. Hyper- and hypo-responsiveness to dietary fat and cholesterol among inbred mice: searching for level and variability genes. J Lipid Res. 1995 Jul;36(7):1522–1532. [PubMed] [Google Scholar]
  35. Krieger H., Morton N. E., Rao D. C., Azevêdo E. Familial determinants of blood pressure in northeastern Brazil. Hum Genet. 1980;53(3):415–418. doi: 10.1007/BF00287065. [DOI] [PubMed] [Google Scholar]
  36. Lenfant C. NHLBI funding policies. Enhancing stability, predictability, and cost control. Circulation. 1994 Jul;90(1):1–1. doi: 10.1161/01.cir.90.1.1. [DOI] [PubMed] [Google Scholar]
  37. Lissner L., Odell P. M., D'Agostino R. B., Stokes J., 3rd, Kreger B. E., Belanger A. J., Brownell K. D. Variability of body weight and health outcomes in the Framingham population. N Engl J Med. 1991 Jun 27;324(26):1839–1844. doi: 10.1056/NEJM199106273242602. [DOI] [PubMed] [Google Scholar]
  38. Longini I. M., Jr, Higgins M. W., Hinton P. C., Moll P. P., Keller J. B. Environmental and genetic sources of familial aggregation of blood pressure in Tecumseh, Michigan. Am J Epidemiol. 1984 Jul;120(1):131–144. doi: 10.1093/oxfordjournals.aje.a113862. [DOI] [PubMed] [Google Scholar]
  39. Lusis A. J., Taylor B. A., Quon D., Zollman S., LeBoeuf R. C. Genetic factors controlling structure and expression of apolipoproteins B and E in mice. J Biol Chem. 1987 Jun 5;262(16):7594–7604. [PubMed] [Google Scholar]
  40. MacCluer J. W., Kammerer C. M., Blangero J., Dyke B., Mott G. E., VandeBerg J. L., McGill H. C., Jr Pedigree analysis of HDL cholesterol concentration in baboons on two diets. Am J Hum Genet. 1988 Oct;43(4):401–413. [PMC free article] [PubMed] [Google Scholar]
  41. Mahaney M. C., Blangero J., Comuzzie A. G., VandeBerg J. L., Stern M. P., MacCluer J. W. Plasma HDL cholesterol, triglycerides, and adiposity. A quantitative genetic test of the conjoint trait hypothesis in the San Antonio Family Heart Study. Circulation. 1995 Dec 1;92(11):3240–3248. doi: 10.1161/01.cir.92.11.3240. [DOI] [PubMed] [Google Scholar]
  42. Marenberg M. E., Risch N., Berkman L. F., Floderus B., de Faire U. Genetic susceptibility to death from coronary heart disease in a study of twins. N Engl J Med. 1994 Apr 14;330(15):1041–1046. doi: 10.1056/NEJM199404143301503. [DOI] [PubMed] [Google Scholar]
  43. Mata P., Ordovas J. M., Lopez-Miranda J., Lichtenstein A. H., Clevidence B., Judd J. T., Schaefer E. J. ApoA-IV phenotype affects diet-induced plasma LDL cholesterol lowering. Arterioscler Thromb. 1994 Jun;14(6):884–891. doi: 10.1161/01.atv.14.6.884. [DOI] [PubMed] [Google Scholar]
  44. McCombs R. J., Marcadis D. E., Ellis J., Weinberg R. B. Attenuated hypercholesterolemic response to a high-cholesterol diet in subjects heterozygous for the apolipoprotein A-IV-2 allele. N Engl J Med. 1994 Sep 15;331(11):706–710. doi: 10.1056/NEJM199409153311104. [DOI] [PubMed] [Google Scholar]
  45. Moll P. P., Sing C. F., Lussier-Cacan S., Davignon J. An application of a model for a genotype-dependent relationship between a concomitant (age) and a quantitative trait (LDL cholesterol) in pedigree data. Genet Epidemiol. 1984;1(4):301–314. doi: 10.1002/gepi.1370010403. [DOI] [PubMed] [Google Scholar]
  46. Monsalve M. V., Robinson D., Woolcock N. E., Powell J. T., Greenhalgh R. M., Humphries S. E. Within-individual variation in serum cholesterol levels: association with DNA polymorphisms at the apolipoprotein B and AI-CIII-AIV loci in patients with peripheral arterial disease. Clin Genet. 1991 Apr;39(4):260–273. doi: 10.1111/j.1399-0004.1991.tb03024.x. [DOI] [PubMed] [Google Scholar]
  47. Mänttäri M., Koskinen P., Ehnholm C., Huttunen J. K., Manninen V. Apolipoprotein E polymorphism influences the serum cholesterol response to dietary intervention. Metabolism. 1991 Feb;40(2):217–221. doi: 10.1016/0026-0495(91)90179-z. [DOI] [PubMed] [Google Scholar]
  48. Ordovas J. M., Lopez-Miranda J., Mata P., Perez-Jimenez F., Lichtenstein A. H., Schaefer E. J. Gene-diet interaction in determining plasma lipid response to dietary intervention. Atherosclerosis. 1995 Dec;118 (Suppl):S11–S27. [PubMed] [Google Scholar]
  49. Paigen B. Genetics of responsiveness to high-fat and high-cholesterol diets in the mouse. Am J Clin Nutr. 1995 Aug;62(2):458S–462S. doi: 10.1093/ajcn/62.2.458S. [DOI] [PubMed] [Google Scholar]
  50. Province M. A., Tishler P., Rao D. C. Repeated-measures model for the investigation of temporal trends using longitudinal family studies: application to systolic blood pressure. Genet Epidemiol. 1989;6(2):333–347. doi: 10.1002/gepi.1370060204. [DOI] [PubMed] [Google Scholar]
  51. Pérusse L., Moll P. P., Sing C. F. Evidence that a single gene with gender- and age-dependent effects influences systolic blood pressure determination in a population-based sample. Am J Hum Genet. 1991 Jul;49(1):94–105. [PMC free article] [PubMed] [Google Scholar]
  52. Reilly S. L., Ferrell R. E., Kottke B. A., Kamboh M. I., Sing C. F. The gender-specific apolipoprotein E genotype influence on the distribution of lipids and apolipoproteins in the population of Rochester, MN. I. Pleiotropic effects on means and variances. Am J Hum Genet. 1991 Dec;49(6):1155–1166. [PMC free article] [PubMed] [Google Scholar]
  53. Rice T., Borecki I. B., Bouchard C., Rao D. C. Segregation analysis of fat mass and other body composition measures derived from underwater weighing. Am J Hum Genet. 1993 May;52(5):967–973. [PMC free article] [PubMed] [Google Scholar]
  54. Rice T., Bouchard C., Borecki I. B., Rao D. C. Commingling and segregation analysis of blood pressure in a French-Canadian population. Am J Hum Genet. 1990 Jan;46(1):37–44. [PMC free article] [PubMed] [Google Scholar]
  55. Roy M., Sing C. F., Betard C., Davignon J. Impact of a common mutation of the LDL receptor gene, in French-Canadian patients with familial hypercholesterolemia, on means, variances and correlations among traits of lipid metabolism. Clin Genet. 1995 Feb;47(2):59–67. doi: 10.1111/j.1399-0004.1995.tb03925.x. [DOI] [PubMed] [Google Scholar]
  56. Schork N. J., Weder A. B., Trevisan M., Laurenzi M. The contribution of pleiotropy to blood pressure and body-mass index variation: the Gubbio Study. Am J Hum Genet. 1994 Feb;54(2):361–373. [PMC free article] [PubMed] [Google Scholar]
  57. Selby J. V., Austin M. A., Newman B., Zhang D., Quesenberry C. P., Jr, Mayer E. J., Krauss R. M. LDL subclass phenotypes and the insulin resistance syndrome in women. Circulation. 1993 Aug;88(2):381–387. doi: 10.1161/01.cir.88.2.381. [DOI] [PubMed] [Google Scholar]
  58. Series J., Cameron I., Caslake M., Gaffney D., Packard C. J., Shepherd J. The Xba1 polymorphism of the apolipoprotein B gene influences the degradation of low density lipoprotein in vitro. Biochim Biophys Acta. 1989 Jun 8;1003(2):183–188. doi: 10.1016/0005-2760(89)90253-1. [DOI] [PubMed] [Google Scholar]
  59. Sims J., Hewitt J. K., Kelly K. A., Carroll D., Turner J. R. Familial and individual influences on blood pressure. Acta Genet Med Gemellol (Roma) 1986;35(1-2):7–21. doi: 10.1017/s0001566000006231. [DOI] [PubMed] [Google Scholar]
  60. Sing C. F., Davignon J. Role of the apolipoprotein E polymorphism in determining normal plasma lipid and lipoprotein variation. Am J Hum Genet. 1985 Mar;37(2):268–285. [PMC free article] [PubMed] [Google Scholar]
  61. Srivastava R. A., Jiao S., Tang J. J., Pfleger B. A., Kitchens R. T., Schonfeld G. In vivo regulation of low-density lipoprotein receptor and apolipoprotein B gene expressions by dietary fat and cholesterol in inbred strains of mice. Biochim Biophys Acta. 1991 Oct 15;1086(1):29–43. doi: 10.1016/0005-2760(91)90151-7. [DOI] [PubMed] [Google Scholar]
  62. Steinmetz A., Jakobs C., Motzny S., Kaffarnik H. Differential distribution of apolipoprotein E isoforms in human plasma lipoproteins. Arteriosclerosis. 1989 May-Jun;9(3):405–411. doi: 10.1161/01.atv.9.3.405. [DOI] [PubMed] [Google Scholar]
  63. Stunkard A. J., Foch T. T., Hrubec Z. A twin study of human obesity. JAMA. 1986 Jul 4;256(1):51–54. [PubMed] [Google Scholar]
  64. Tambs K., Eaves L. J., Moum T., Holmen J., Neale M. C., Naess S., Lund-Larsen P. G. Age-specific genetic effects for blood pressure. Hypertension. 1993 Nov;22(5):789–795. doi: 10.1161/01.hyp.22.5.789. [DOI] [PubMed] [Google Scholar]
  65. Tikkanen M. J., Huttunen J. K., Ehnholm C., Pietinen P. Apolipoprotein E4 homozygosity predisposes to serum cholesterol elevation during high fat diet. Arteriosclerosis. 1990 Mar-Apr;10(2):285–288. doi: 10.1161/01.atv.10.2.285. [DOI] [PubMed] [Google Scholar]
  66. Tikkanen M. J., Xu C. F., Hämäläinen T., Talmud P., Sarna S., Huttunen J. K., Pietinen P., Humphries S. XbaI polymorphism of the apolipoprotein B gene influences plasma lipid response to diet intervention. Clin Genet. 1990 May;37(5):327–334. doi: 10.1111/j.1399-0004.1990.tb03514.x. [DOI] [PubMed] [Google Scholar]
  67. Tiret L., André J. L., Ducimetière P., Herbeth B., Rakotovao R., Guegen R., Spyckerelle Y., Cambien F. Segregation analysis of height-adjusted weight with generation- and age-dependent effects: the Nancy Family Study. Genet Epidemiol. 1992;9(6):389–403. doi: 10.1002/gepi.1370090603. [DOI] [PubMed] [Google Scholar]
  68. Towne B., Blangero J., Siervogel R. M. Genotype by sex interaction in measures of lipids, lipoproteins, and apolipoproteins. Genet Epidemiol. 1993;10(6):611–616. doi: 10.1002/gepi.1370100647. [DOI] [PubMed] [Google Scholar]
  69. Williams C. J., Christian J. C., Norton J. A., Jr TWINAN90: a FORTRAN program for conducting ANOVA-based and likelihood-based analyses of twin data. Comput Methods Programs Biomed. 1992 Jul;38(2-3):167–176. doi: 10.1016/0169-2607(92)90084-k. [DOI] [PubMed] [Google Scholar]
  70. Xu C. F., Boerwinkle E., Tikkanen M. J., Huttunen J. K., Humphries S. E., Talmud P. J. Genetic variation at the apolipoprotein gene loci contribute to response of plasma lipids to dietary change. Genet Epidemiol. 1990;7(4):261–275. doi: 10.1002/gepi.1370070405. [DOI] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES