Human Genetics

, Volume 133, Issue 8, pp 1049–1057 | Cite as

Metabolic heritability at birth: implications for chronic disease research

  • Kelli K. Ryckman
  • Caitlin J. Smith
  • Laura L. Jelliffe-Pawlowski
  • Allison M. Momany
  • Stanton L. Berberich
  • Jeffrey C. Murray
Original Investigation


Recent genome-wide association studies of the adult human metabolome have identified genetic variants associated with relative levels of several acylcarnitines, which are important clinical correlates for chronic conditions such as type 2 diabetes and obesity. We have previously shown that these same metabolite levels are highly heritable at birth; however, no studies to our knowledge have examined genetic associations with these metabolites measured at birth. Here, we examine, in 743 newborns, 58 single nucleotide polymorphisms (SNPs) in 11 candidate genes previously associated with differing relative levels of short-chain acylcarnitines in adults. Six SNPs (rs2066938, rs3916, rs3794215, rs555404, rs558314, rs1799958) in the short-chain acyl-CoA dehydrogenase gene (ACADS) were associated with neonatal C4 levels. Most significant was the G allele of rs2066938, which was associated with significantly higher levels of C4 (P = 1.5 × 10−29). This SNP explains 25 % of the variation in neonatal C4 levels, which is similar to the variation previously reported in adult C4 levels. There were also significant (P < 1 × 10−4) associations between neonatal levels of C5-OH and SNPs in the solute carrier family 22 genes (SLC22A4 and SLC22A5) and the 3-methylcrotonyl-CoA carboxylase 1 gene (MCCC1). We have replicated, in newborns, SNP associations between metabolic traits and the ACADS and SLC22A4 genes observed in adults. This research has important implications not only for the identification of rare inborn errors of metabolism but also for personalized medicine and early detection of later life risks for chronic conditions.


Newborn Screening Propionylcarnitine Rare Inborn Error TaqMan Minor Groove Binder Probe Stearoylcarnitine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We express our thanks to Kim Piper at the Iowa Department of Public Health and the members of the Congenital and Inherited Disorders Advisory Committee for their enthusiastic support and management of this project. We thank Teresa Snell, Franklin Delin and Dariush Shirazi from the State Hygienic Laboratory for their assistance in the acquisition of the newborn screening data and samples. We thank Sara Copeland at the Health Resources Services Administration for her guidance on this project. Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health under Award Number R00HD065786. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Conflict of interest

The authors declare they have no conflict of interest.

Supplementary material

439_2014_1450_MOESM1_ESM.docx (23 kb)
Supplementary material 1 (DOCX 22 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Kelli K. Ryckman
    • 1
  • Caitlin J. Smith
    • 1
  • Laura L. Jelliffe-Pawlowski
    • 2
    • 3
  • Allison M. Momany
    • 4
  • Stanton L. Berberich
    • 5
  • Jeffrey C. Murray
    • 4
  1. 1.Department of EpidemiologyUniversity of IowaIowa CityUSA
  2. 2.Genetic Disease Screening ProgramCalifornia Department of Public HealthSacramentoUSA
  3. 3.Division of Preventive Medicine and Public Health, Department of Epidemiology and BiostatisticsUniversity of California San Francisco School of MedicineSan FranciscoUSA
  4. 4.Department of PediatricsUniversity of IowaIowa CityUSA
  5. 5.State Hygienic LaboratoryUniversity of IowaIowa CityUSA

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