Bivariate genetic analysis of fasting insulin and glucose levels

Snieder, Harold; Boomsma, Dorret I.; Doornen, Lorenz J.P. van; Neale, Michael C.

doi:10.1002/(sici)1098-2272(1999)16:4<426::aid-gepi8>3.0.co;2-b

Cited by 51 publications

(21 citation statements)

References 72 publications

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“…On the basis of our data, the Hph1 polymorphism and neighbouring VNTR are the first loci to be involved in the genetic regulation of fasting insulin levels, a trait whose heritability is estimated between 0.20 and 0.52 (ref. 12). Signals to β-cells originating from adipocytes may involve insulin resistance and a resulting tendency for hyperglycaemia, as well as other endocrine or metabolic messages associated with fat accumulation, such as free fatty acids or leptin.…”

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confidence: 99%

The insulin gene VNTR is associated with fasting insulin levels and development of juvenile obesity

et al. 2000

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In millions of people, obesity leads to type 2 diabetes (T2D; also known as non-insulin-dependent diabetes mellitus). During the early stages of juvenile obesity, the increase of insulin secretion in proportion to accumulated fat balances insulin resistance and protects patients from hyperglycaemia. After several decades, however,beta-cell function deteriorates and T2D develops in approximately 20% of obese patients. In modern societies, obesity has thus become the leading risk factor for T2D (ref. 5). The factors that predispose obese patients to alteration of insulin secretion upon gaining weight remain unknown. To determine which genetic factors predispose obese patients to beta-cell dysfunction, and possibly T2D, we studied single-nucleotide polymorphisms (SNPs) in the region of the insulin gene (INS) among 615 obese children. We found that, in the early phase of obesity, alleles of the INS variable number of tandem repeat (VNTR) locus are associated with different effects of body fatness on insulin secretion. Young obese patients homozygous for class I VNTR alleles secrete more insulin than those with other genotypes.

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The insulin gene VNTR is associated with fasting insulin levels and development of juvenile obesity

et al. 2000

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“…Other factors, e.g. race, should also be interesting to consider in the study of complex traits to increase the power of the analysis beyond pleiotropic influences [22]. …”

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confidence: 99%

Evaluating gene by sex and age interactions on cardiovascular risk factors in Brazilian families

et al. 2010

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BackgroundIn family studies, it is important to evaluate the impact of genes and environmental factors on traits of interest. In particular, the relative influences of both genes and the environment may vary in different strata of the population of interest, such as young and old individuals, or males and females.MethodsIn this paper, extensions of the variance components model are used to evaluate heterogeneity in the genetic and environmental variance components due to the effects of sex and age (the cutoff between young and old was 43 yrs). The data analyzed were from 81 Brazilian families (1,675 individuals) of the Baependi Family Heart Study.ResultsThe models allowing for heterogeneity of variance components by sex suggest that genetic and environmental variances are not different in males and females for diastolic blood pressure, LDL-cholesterol, and HDL-cholesterol, independent of the covariates included in the models. However, for systolic blood pressure, fasting glucose and triglycerides, the evidence for heterogeneity was dependent on the covariates in the model. For instance, in the presence of sex and age covariates, heterogeneity in the genetic variance component was suggested for fasting glucose. But, for systolic blood pressure, there was no evidence of heterogeneity in any of the two variance components. Except for the LDL-cholesterol, models allowing for heterogeneity by age provide evidence of heterogeneity in genetic variance for triglycerides and systolic and diastolic blood pressure. There was evidence of heterogeneity in environmental variance in fasting glucose and HDL-cholesterol.ConclusionsOur results suggest that heterogeneity in trait variances should not be ignored in the design and analyses of gene-finding studies involving these traits, as it may generate additional information about gene effects, and allow the investigation of more sophisticated models such as the model including sex-specific oligogenic variance components.

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“…Additionally, 204 subjects who did not participate in the WAIS‐3 intelligence test took the GIT vocabulary subtest as a part of a cardiovascular project described elsewhere (van den Berg et al . 2004; Snieder et al . 1999).…”

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confidence: 99%

Genetic contributions to the association between height and intelligence: evidence from Dutch twin data from childhood to middle age

Silventoinen

Posthuma

Beijsterveldt

et al. 2006

Genes Brain and Behavior

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A positive association between intelligence (IQ) and height has been reported previously. It is generally assumed that this association reflects the effect of childhood environment on IQ, but there is still little research supporting directly this hypothesis. We studied the association between height and IQ in 209 Dutch twin pairs at the ages of 5, 7, 10 and 12 years, 208 twin pairs at 16 and 18 years of age and 567 twin pairs and their siblings in adulthood. The heritability of height was high in all cohorts and across all ages (a 2 = 0.93 -0.96). In adulthood, heritability was also high for full-scale IQ (FSIQ: a 2 = 0.83-0.84) and somewhat lower for verbal IQ (VIQ: a 2 = 0.66-0.84). In early childhood, the heritability was lower, and common environmental factors had a substantial effect on FSIQ and VIQ. A positive association of height and IQ was found in early childhood and adolescence. In adulthood, a correlation was found between height and FSIQ in young adulthood and between height and VIQ in middle age. All correlations could be ascribed to genetic factors influencing both height and IQ. Thus, these results show that the association between height and IQ should not be directly regarded as evidence for childhood living conditions affecting IQ, but the effect of genetic factors affecting independently or interacting with environmental factors should be considered as well.

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Bivariate genetic analysis of fasting insulin and glucose levels

Cited by 51 publications

References 72 publications

The insulin gene VNTR is associated with fasting insulin levels and development of juvenile obesity

The insulin gene VNTR is associated with fasting insulin levels and development of juvenile obesity

Evaluating gene by sex and age interactions on cardiovascular risk factors in Brazilian families

Genetic contributions to the association between height and intelligence: evidence from Dutch twin data from childhood to middle age

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