Heritability of fasting glucose levels in a young genetically isolated population

Santos, R. L. P.; Zillikens, M. Carola; Rivadeneira, Fernando; Pols, Huibert A. P.; Oostra, Ben A.; Duijn, Cornelia M. van; Aulchenko, Yurii S.

doi:10.1007/s00125-006-0142-6

Cited by 32 publications

(27 citation statements)

References 23 publications

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“…The genetic make-up of genetically isolated populations may differ from a general population as a result of genetic drift and founder effects. Even though our population is a genetic isolate we found no evidence that it deviates much from the general population in its genetic composition [23,34]. However, as was pointed out again recently [35], heritability estimates are by definition population-specific and replication of our findings in other populations is necessary.…”

Section: Discussionsupporting

confidence: 44%

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Sex-specific genetic effects influence variation in body composition

et al. 2008

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Aims/hypothesis Despite well-known sex differences in body composition it is not known whether sex-specific genetic or environmental effects contribute to these differences. Methods We assessed body composition in 2,506 individuals, from a young Dutch genetic isolate participating in the Erasmus Rucphen Family study, by dual-energy X-ray absorptiometry and anthropometry. We used variance decomposition procedures to partition variation of body composition into genetic and environmental components common to both sexes and to men and women separately and calculated the correlation between genetic components in men and women. Results After accounting for age, sex and inbreeding, heritability ranged from 0.39 for fat mass index to 0.84 for height. We found sex-specific genetic effects for fat percentage (fat%), lean mass, lean mass index (LMI) and fat distribution, but not for BMI and height. Genetic correlations between sexes were significantly different from 1 for fat%, lean mass, LMI, android fat, android:gynoid fat ratio and WHR, indicating that there are sex-specific genes contributing to variation of these traits. Genetic variance was significantly higher in women for the waist, hip and thigh circumference and WHR, implying that genes account for more variance of fat distribution in women than in men. Environmental variance was significantly higher in men for the android: gynoid fat ratio. Conclusions/interpretation Sex-specific genetic effects underlie sexual dimorphism in several body composition traits. The findings are relevant for studies on the relationship of body composition with common diseases like cardiovascular disease and type 2 diabetes and for genetic association studies.

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Section: Discussionsupporting

confidence: 44%

“…The aim of this programme is to identify genetic risk factors in the development of complex disorders [21][22][23]. Genealogical records demonstrated that almost all of the inhabitants of this isolated population could be traced back to about 150 individuals who founded this community about the year 1750.…”

Section: Methodsmentioning

confidence: 99%

Sex-specific genetic effects influence variation in body composition

et al. 2008

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“…Previous studies demonstrated genetic influence for familial clustering of features of the metabolic syndrome. 34,35 Whether familial aggregation in our study is because of shared environmental and/or genetic factors cannot be concluded. Nonetheless, our data suggest a potential role for the glucose metabolism in the pathogenesis of both pregnancy disorders.…”

Section: Discussionmentioning

confidence: 77%

Shared Constitutional Risks for Maternal Vascular-Related Pregnancy Complications and Future Cardiovascular Disease

Berends

Groot²,

Sijbrands³

et al. 2008

Hypertension

200

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Abstract-Maternal predisposition to vascular and metabolic disease may underlie both vascular-related pregnancy complications, such as preeclampsia and intrauterine growth restriction, as well as future maternal cardiovascular disease. We aimed to substantiate this hypothesis with biochemical and anthropometric evidence by conducting an intergenerational case-control study in a Dutch isolated population including 106 women after preeclampsia or intrauterine growth restriction (median follow-up: 7.1 years) and their fathers (nϭ43) and mothers (nϭ64), as well as 106 control subjects after uncomplicated pregnancies with their fathers (nϭ51) and mothers (nϭ68). Cardiovascular risk profiles were assessed, including fasting glucose, lipids, anthropometrics, blood pressure, intima-media thickness, and metabolic syndrome. We found significantly higher fasting glucose levels, larger waist circumferences, and a 5-fold increased prevalence of hypertension in women with a history of preeclampsia as compared with control subjects (PϽ0.001). Likewise, their parents had higher glucose levels than control parents (PϽ0.05). Their mothers had larger waist circumferences and higher blood pressures (PϽ0.05). Also, women after pregnancies complicated by intrauterine growth restriction had higher glucose levels and increased prevalence of hypertension (PϽ0.01). Their fathers showed higher glucose levels as well (PϽ0.05). Mean carotid intima-media thickness was increased in a subset of women after preeclampsia diagnosed with chronic hypertension as compared with those without hypertension (PϽ0.01). Metabolic syndrome was more prevalent both in women with a history of preeclampsia and their mothers (PϽ0.05). We demonstrated intergenerational similarities in cardiovascular risk profiles between women after preeclampsia or intrauterine growth restriction and their parents. These findings suggest shared constitutional risks for vascular-related pregnancy complications and future cardiovascular disease. (Hypertension. 2008;51:1034-1041.)

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“…There was a high level of intra-pair agreement on contact frequency for the 4317 pairs in which both twins responded (rho = 0.81). The average level of contact frequency within the pair was used for (Fenger et al, 2007) e (Goode et al,2007) f (Henneman et al, 2008) g (Isaacs et al, 2007) h (McQueen et al, 2003) i (Snieder et al, 1999) j (Souren et al, 2007) k (VelasquezMelendez et al, 2007) l (Chien et al, 2007) m (Iliadou et al,2005) n (Hokanson et al, 2003) o (Beekman et al, 2002) p (Iliadou et al, 2001) q (Middelberg et al, 2002) r (Santos et al, 2006) s (Snieder et al, 2001) t (Simonis-Bik et al, 2008) u (Berrahmoune et al, 2007) v (Fox et al, 2008) w (Lange et al, 2006) x (Su et al, 2008) y (Wessel et al, 2007) z (Worns et al, 2006) https://www. these pairs.…”

Section: Twin Contact and Age At Separationmentioning

confidence: 99%

Genetic Dominance Influences Blood Biomarker Levels in a Sample of 12,000 Swedish Elderly Twins

et al. 2009

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In twin studies of cardiovascular disease biomarkers the dizygotic correlations are often estimated to be less than half of monozygotic correlations indicating a potential influence of nonadditive genetic factors. Using a large and homogenous sample, we estimated the additive and dominance genetic influences on levels of high density lipoprotein, low density lipoprotein, apolipoprotein A-I, apolipoprotein B, total cholesterol, triglycerides, glucose, hemoglobin Alc and c-reactive protein, all of which are biomarkers associated with cardiovascular disease. The blood biomarkers were measured on 12,000 Swedish twins born between 1911 and 1958. The large sample allowed us to obtain heritability estimates with considerable precision and provided adequate statistical power for estimation of dominance genetic components. Our study showed complete absence of the shared environment component for the investigated traits. Dominant genetic component was shown to be significant for low density lipoprotein (0.18), glucose (0.31), Hemoglobin Alc (0.55), and c-reactive protein (0.27). To our knowledge, this is the first statistically significant evidence for dominance genetic variance found for low density lipoprotein, glucose, hemoglobin Alc, and c-reactive protein in a population based twin sample. The study highlights the importance of acknowledging nonadditive genes underlying the risk of developing cardiovascular diseases.

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Heritability of fasting glucose levels in a young genetically isolated population

Cited by 32 publications

References 23 publications

Sex-specific genetic effects influence variation in body composition

Sex-specific genetic effects influence variation in body composition

Shared Constitutional Risks for Maternal Vascular-Related Pregnancy Complications and Future Cardiovascular Disease

Genetic Dominance Influences Blood Biomarker Levels in a Sample of 12,000 Swedish Elderly Twins

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