Dataset Information

The heritability of metabolic profiles in newborn twins.

ABSTRACT: Identifying genetic and metabolic biomarkers in neonates has the potential to improve diagnosis and treatment of common complex neonatal diseases, and potentially lead to risk assessment and preventative measures for common adulthood illnesses such as diabetes and cardiovascular disease. There is a wealth of information on using fatty acid, amino acid and organic acid metabolite profiles to identify rare inherited congenital diseases through newborn screening, but little is known about these metabolic profiles in the context of the 'healthy' newborn. Recent studies have implicated many of the amino acid and fatty acid metabolites utilized in newborn screening in common complex adult diseases such as cardiovascular disease, insulin resistance and obesity. To determine the heritability of metabolic profiles in newborns, we examined 381 twin pairs obtained from the Iowa Neonatal Metabolic Screening Program. Heritability was estimated using multilevel mixed-effects linear regression adjusting for gestational age, gender, weight and age at time of sample collection. The highest heritability was for short-chain acylcarnitines, specifically C4 (h²=0.66, P=2 × 10?¹?), C4-DC (h²=0.83, P<10?¹?) and C5 (h²=0.61, P=1 × 10??). Thyroid stimulating hormone (h²=0.58, P=2 × 10??) and immunoreactive trypsinogen (h²=0.52, P=3 × 10??) also have a strong genetic component. This is direct evidence for a strong genetic contribution to the metabolic profile at birth and that newborn screening data can be utilized for studying the genetic regulation of many clinically relevant metabolites.

SUBMITTER: Alul FY

PROVIDER: S-EPMC3668651 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The heritability of metabolic profiles in newborn twins.

Alul F Y FY Cook D E DE Shchelochkov O A OA Fleener L G LG Berberich S L SL Murray J C JC Ryckman K K KK

Heredity 20121114 3

Identifying genetic and metabolic biomarkers in neonates has the potential to improve diagnosis and treatment of common complex neonatal diseases, and potentially lead to risk assessment and preventative measures for common adulthood illnesses such as diabetes and cardiovascular disease. There is a wealth of information on using fatty acid, amino acid and organic acid metabolite profiles to identify rare inherited congenital diseases through newborn screening, but little is known about these met ...[more]

PMID: 23149456

Similar Datasets

Project description:IMPORTANCE:Estimates of familial cancer risk from population-based studies are essential components of cancer risk prediction. OBJECTIVE:To estimate familial risk and heritability of cancer types in a large twin cohort. DESIGN, SETTING, AND PARTICIPANTS:Prospective study of 80,309 monozygotic and 123,382 same-sex dizygotic twin individuals (N?=?203,691) within the population-based registers of Denmark, Finland, Norway, and Sweden. Twins were followed up a median of 32 years between 1943 and 2010. There were 50,990 individuals who died of any cause, and 3804 who emigrated and were lost to follow-up. EXPOSURES:Shared environmental and heritable risk factors among pairs of twins. MAIN OUTCOMES AND MEASURES:The main outcome was incident cancer. Time-to-event analyses were used to estimate familial risk (risk of cancer in an individual given a twin's development of cancer) and heritability (proportion of variance in cancer risk due to interindividual genetic differences) with follow-up via cancer registries. Statistical models adjusted for age and follow-up time, and accounted for censoring and competing risk of death. RESULTS:A total of 27,156 incident cancers were diagnosed in 23,980 individuals, translating to a cumulative incidence of 32%. Cancer was diagnosed in both twins among 1383 monozygotic (2766 individuals) and 1933 dizygotic (2866 individuals) pairs. Of these, 38% of monozygotic and 26% of dizygotic pairs were diagnosed with the same cancer type. There was an excess cancer risk in twins whose co-twin was diagnosed with cancer, with estimated cumulative risks that were an absolute 5% (95% CI, 4%-6%) higher in dizygotic (37%; 95% CI, 36%-38%) and an absolute 14% (95% CI, 12%-16%) higher in monozygotic twins (46%; 95% CI, 44%-48%) whose twin also developed cancer compared with the cumulative risk in the overall cohort (32%). For most cancer types, there were significant familial risks and the cumulative risks were higher in monozygotic than dizygotic twins. Heritability of cancer overall was 33% (95% CI, 30%-37%). Significant heritability was observed for the cancer types of skin melanoma (58%; 95% CI, 43%-73%), prostate (57%; 95% CI, 51%-63%), nonmelanoma skin (43%; 95% CI, 26%-59%), ovary (39%; 95% CI, 23%-55%), kidney (38%; 95% CI, 21%-55%), breast (31%; 95% CI, 11%-51%), and corpus uteri (27%; 95% CI, 11%-43%). CONCLUSIONS AND RELEVANCE:In this long-term follow-up study among Nordic twins, there was significant excess familial risk for cancer overall and for specific types of cancer, including prostate, melanoma, breast, ovary, and uterus. This information about hereditary risks of cancers may be helpful in patient education and cancer risk counseling.

Project description:Background: The prevalence of obesity and cardiometabolic diseases continues to rise globally and obesity is a significant risk factor for cardiometabolic diseases. However, to our knowledge, evidence of the relative roles of genes and the environment underlying obesity and cardiometabolic disease traits and the correlations between them are still lacking, as is how they change with age. Method: Data were obtained from the Chinese National Twin Registry (CNTR). A total of 1421 twin pairs were included. Univariate structural equation models (SEMs) were performed to evaluate the heritability of BMI and cardiometabolic traits, which included blood hemoglobin A1c (HbA1c), fasting blood glucose (FBG), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Bivariate SEMs were used to assess the genetic/environmental correlations between them. The study population was divided into three groups for analysis: ≤50, 51–60, and >60 years old to assess the changes in heritability and genetic/environmental correlations with ageing. Results: Univariate SEMs showed a high heritability of BMI (72%) and cardiometabolic traits, which ranged from 30% (HbA1c) to 69% (HDL-C). With age increasing, the heritability of all phenotypes has different degrees of declining trends. Among these, BMI, SBP, and DBP presented significant monotonous declining trends. The bivariate SEMs indicated that BMI correlated with all cardiometabolic traits. The genetic correlations were estimated to range from 0.14 (BMI and LDL-C) to 0.39 (BMI and DBP), while the environmental correlations ranged from 0.13 (BMI and TC/LDL-C) to 0.31 (BMI and TG). The genetic contributions underlying the correlations between BMI and SBP and DBP, TC, TG, and HDL-C showed a progressive decrease as age groups increased. In contrast, environmental correlations displayed a significant increasing trend for HbA1c, SBP, and DBP. Conclusions: The findings suggest that genetic and environmental factors have essential effects on BMI and all cardiometabolic traits. However, as age groups increased, genetic influences presented varying degrees of decrement for BMI and most cardiometabolic traits, suggesting the increasing importance of environments. Genetic factors played a consistently larger role than environmental factors in the phenotypic correlations between BMI and cardiometabolic traits. Nevertheless, the relative magnitudes of genetic and environmental factors may change over time.

Dataset Information

The heritability of metabolic profiles in newborn twins.

Publications

The heritability of metabolic profiles in newborn twins.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets