The Cincinnati lipid research clinic family study: Analysis of commingling and family resemblance for fasting blood glucose

Laskarzewski, Peter M.; Rao, D. C.; Glueck, Charles J.; Nance, Walter E.

doi:10.1002/gepi.1370010406

Cited by 16 publications

(17 citation statements)

References 23 publications

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“…shared family environment) and several studies have suggested that the familial resemblance in glucose levels is predominantly cultural [48,52,53]. However, in two studies of Caucasian pedigrees, polygenic effects were more pronounced [50,51]. POINTER does not permit discrimination of polygenic and transmitted environmental influences: evidence for intergenerational differences in the heritability of the multifactorial component (i.e.z ~ 1) may be taken to indicate support for additional sharing of environment between siblings but in practise the interpretation of z presents difficulties.…”

Section: Discussionmentioning

confidence: 98%

“…Serjeantson and Zimmet [46] used POINTER to adduce evidence for an autosomal dominant gene operating on a multifactorial background in Nauruan families. In contrast, segregation studies in populations at lower risk of diabetes (Japanese [47,48] and Caucasians [49,50]) have not found clear evidence for major gene effects,…”

Section: Discussionmentioning

confidence: 98%

“…Familial aggregation of glucose levels has been reported before [49][50][51] although in some studies aggregation has been weak [48,52]. The path analysis methodology used in these studies is better-suited than segregation analysis to separation of genetic and cultural heritability (i.e.…”

Section: Discussionmentioning

confidence: 99%

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Family studies of non-insulin-dependent diabetes mellitus in South Indians

et al. 1994

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Summary Though a genetic basis for non-insulin-dependent diabetes mellitus (NIDDM) is clear, the likely mode of inheritance is not known. The segregation of NIDDM was studied in 64 nuclear South Indian pedigrees (449 individuals) ascertained through an affected proband having both parents and more than 1 sibling alive and available for oral glucose tolerance testing. A high proportion of parents were found to be of abnormal glucose tolerance [89 of 128 (70 %) diabetic and 11 of 128 (9 %) impaired]. Complex segregation analysis was performed using (1) POINTER which implements the mixed model and distinguishes major gene, multifactorial and nontransmitted environmental contributions to affection and (2) COMDS which implements an oligogenic model with major gene, modifier gene and environmental contributions to a) affection and b) diathesis (an ordered polychotomy amongst non-affected family members, based on 2-h plasma glucose level). Using POINTER, there was no formal support for a major gene and the most parsimonious solutions were achieved with multifactorial models. Using COMDS, we found i) significant improvements in models when information on glucose levels in nondiabetic family members (diathesis) was included, if) support for segregation of a dialletic gene as well as background familial resemblance, and iii) under the best-supported model, this diallelic locus featured incomplete dominance (d---0.8) and a disease-predisposing allele frequency of 14 %. In South Indians, segregation of NIDDM is inadequately described by simple major gene models: more complex models provide more satisfactory descriptions. This finding, if applicable in other populations, has important implications for the search for diabetes-susceptibility genes. [Diabetologia (1994[Diabetologia ( ) 37: 1221[Diabetologia ( -1230

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

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Family studies of non-insulin-dependent diabetes mellitus in South Indians

et al. 1994

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“…been in the range between 0 to 39% [1,2,3], whereas the estimates for indices of insulin secretion and insulin sensitivity have been somewhat higher, 28 to 65% [4,5]. Segregation analyses have provided evidence for a major gene effect on both fasting and 1-h insulin [6].…”

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confidence: 99%

Twin study of genetic and environmental influences on glucose tolerance and indices of insulin sensitivity and secretion

et al. 2003

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Aims/hypothesis. Family and twin studies have reported different estimates of the relative contribution of genetic and environmental factors to the quantitative traits glucose tolerance, insulin secretion, and insulin sensitivity. Our aims were to estimate these relative influences in a large sample of twins from the population and to assess the effect of age. Methods. In this population-based, cross-sectional study we gave an oral glucose tolerance test to 317 women and 290 men who were same-sex healthy twin pairs between 18 to 67 years of age. The genetic, common environmental and individual environmental variance components for fasting and 120-min glucose and for fasting and 30-min insulin as well as the linear effects of age on these components were estimated by multivariate analysis (using the software FISHER). Results. In women and men the heritability for fasting glucose was 12 and 38%, for 120-min glucose it was 38 and 43%, for fasting insulin it was 54 and 37%, and for 30-min insulin it was 57 and 47%, respectively. Under the assumption of no non-additive genetic effects (no intra-or inter-gene interaction) there was no strong evidence for common environmental effects, barring significant effects for fasting glucose in women. Heritability decreased with age for 120-min glucose in women and fasting insulin in men, whereas it increased for 120-min glucose in men. Conclusion/interpretation. This study indicates a limited additive genetic influence on the result of an OGTT, possibly with sex-specific age effects, and generally little or no influence of the common environment. Accordingly, there is a considerable individual environmental variation. [Diabetologia (2003[Diabetologia ( ) 46:1276[Diabetologia ( -1283

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“…The only previous reports of path anal ysis of glucose tolerance were with respect to fasting plasma glucose concentration, in Japanese Americans in Hawaii [8] and Caucasians at the Cincinnati Lipid Re search Center (LRC) [9].…”

Section: Discussionmentioning

confidence: 99%

Family Resemblance for Glucose Tolerance in a Melanesian Population, the Tolai

King¹,

Rao

Bhatia

et al. 1989

Hum Hered

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Path analysis of family resemblance for plasma glucose concentration, 2 h after an oral glucose challenge, failed to detect significant genetic heritability. There were no intergenerational differences and marital resemblance was moderate. Over one-third of sibling environmental similarity was due to non-inherited factors. Cultural inheritance was very strong, tending to mimic genetic inheritance, and cultural heritability was considerable. Measures of obesity were included in the environmental index, an estimate of familial environment, in this analysis, for comparability with previous studies. Since obesity appears, in part, to be a heritable trait, in future studies a bivariate approach to family resemblance for both glucose tolerance and obesity could yield important additional insight.

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The Cincinnati lipid research clinic family study: Analysis of commingling and family resemblance for fasting blood glucose

Cited by 16 publications

References 23 publications

Family studies of non-insulin-dependent diabetes mellitus in South Indians

Family studies of non-insulin-dependent diabetes mellitus in South Indians

Twin study of genetic and environmental influences on glucose tolerance and indices of insulin sensitivity and secretion

Family Resemblance for Glucose Tolerance in a Melanesian Population, the Tolai

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