TY - JOUR

T1 - Genetic insights into fetal growth and measures of glycaemic regulation and adiposity in adulthood

T2 - a family-based study

AU - Hollensted, Mette

AU - Ekstrøm, Claus T.

AU - Pedersen, Oluf

AU - Eiberg, Hans

AU - Hansen, Torben

AU - Gjesing, Anette Prior

PY - 2018

Y1 - 2018

N2 - Background: The genetics of fetal insulin release and/or action have been suggested to affect fetal growth, adult insulin resistance and adult body composition. The genetic correlation between body composition at birth versus glycaemic regulation and body composition in adulthood have, however, not been well studied. We therefore aimed to investigate these genetic correlations in a family-based cohort. Methods: A Danish family cohort of 434 individuals underwent an oral glucose tolerance test with subsequent calculation of surrogate measures of serum insulin response and insulin sensitivity. Measures of fetal growth were retrieved from midwife journals. Heritability and genetic correlations were estimated using a variance component model. Results: A high heritability of 0.80 was found for birth weight, whereas ponderal index had a heritability of 0.46. Adult insulin sensitivity measured as Matsuda index was genetically correlated with both birth weight and ponderal index (ρG = 0.36 (95% CI: 0.03; 0.69) and ρG = 0.52 (95% CI, 0.15; 0.89), respectively). Only birth weight showed a significant genetic correlation with adult weight (ρG = 0.38 (95% CI: 0.09; 0.67)) whereas only ponderal index was genetically inversely correlated with fasting insulin (ρG = - 0.47 (95% CI: - 0.86; - 0.08) and area under the curve for insulin release during the oral glucose tolerance test (ρG = - 0.66 (95% CI: - 1.13; - 0.19)). Individual as well as combined adjustment for 45 selected birth weight, obesity and type 2 diabetes susceptibility gene variants did not affect the correlations. Conclusions: The genetics of both birth weight and ponderal index appear to be under the same genetic influence as adult insulin resistance. Furthermore, ponderal index and adult insulin release seem to be partly shared, as well as the genetics of birth weight and adult weight. Word count abstract: 281.

AB - Background: The genetics of fetal insulin release and/or action have been suggested to affect fetal growth, adult insulin resistance and adult body composition. The genetic correlation between body composition at birth versus glycaemic regulation and body composition in adulthood have, however, not been well studied. We therefore aimed to investigate these genetic correlations in a family-based cohort. Methods: A Danish family cohort of 434 individuals underwent an oral glucose tolerance test with subsequent calculation of surrogate measures of serum insulin response and insulin sensitivity. Measures of fetal growth were retrieved from midwife journals. Heritability and genetic correlations were estimated using a variance component model. Results: A high heritability of 0.80 was found for birth weight, whereas ponderal index had a heritability of 0.46. Adult insulin sensitivity measured as Matsuda index was genetically correlated with both birth weight and ponderal index (ρG = 0.36 (95% CI: 0.03; 0.69) and ρG = 0.52 (95% CI, 0.15; 0.89), respectively). Only birth weight showed a significant genetic correlation with adult weight (ρG = 0.38 (95% CI: 0.09; 0.67)) whereas only ponderal index was genetically inversely correlated with fasting insulin (ρG = - 0.47 (95% CI: - 0.86; - 0.08) and area under the curve for insulin release during the oral glucose tolerance test (ρG = - 0.66 (95% CI: - 1.13; - 0.19)). Individual as well as combined adjustment for 45 selected birth weight, obesity and type 2 diabetes susceptibility gene variants did not affect the correlations. Conclusions: The genetics of both birth weight and ponderal index appear to be under the same genetic influence as adult insulin resistance. Furthermore, ponderal index and adult insulin release seem to be partly shared, as well as the genetics of birth weight and adult weight. Word count abstract: 281.

KW - Birth weight

KW - Body composition

KW - Fetal growth

KW - Genetic association

KW - Genetic correlation

KW - Heritability

KW - Insulin secretion

KW - Insulin sensitivity

U2 - 10.1186/s12881-018-0718-2

DO - 10.1186/s12881-018-0718-2

M3 - Journal article

C2 - 30514227

AN - SCOPUS:85057628914

VL - 19

SP - 1

EP - 9

JO - B M C Medical Genetics

JF - B M C Medical Genetics

SN - 1471-2350

M1 - 207

ER -