New Search

Export article

Loss-of-function mutations in the melanocortin 4 receptor in a UK birth cohort

Kaitlin H. Wade, , Audrey Melvin, Warren Pan, , , Kara Rainbow, Jian-Hua Chen, Katie Duckett, XiaoMing Liu,
Show More
Published: 27 May 2021
Nature Medicine , Volume 27, pp 1088-1096; doi:10.1038/s41591-021-01349-y

Abstract: Mutations in the melanocortin 4 receptor gene (MC4R) are associated with obesity but little is known about the prevalence and impact of such mutations throughout human growth and development. We examined the MC4R coding sequence in 5,724 participants from the Avon Longitudinal Study of Parents and Children, functionally characterized all nonsynonymous MC4R variants and examined their association with anthropometric phenotypes from childhood to early adulthood. The frequency of heterozygous loss-of-function (LoF) mutations in MC4R was ~1 in 337 (0.30%), considerably higher than previous estimates. At age 18 years, mean differences in body weight, body mass index and fat mass between carriers and noncarriers of LoF mutations were 17.76 kg (95% CI 9.41, 26.10), 4.84 kg m−2 (95% CI 2.19, 7.49) and 14.78 kg (95% CI 8.56, 20.99), respectively. MC4R LoF mutations may be more common than previously reported and carriers of such variants may enter adult life with a substantial burden of excess adiposity. Analysis of mutations in MC4R and associated anthropometric phenotypes in the ALSPAC birth cohort reveals a prevalence of heterozygous loss of function of 0.30% and provides evidence that these mutations are associated with substantial excess adiposity in early life.
Keywords: Epidemiology / Genetics research / Obesity / Biomedicine / general / Cancer Research / Metabolic Diseases / Infectious Diseases / Molecular Medicine / Neurosciences

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

Share this article

Click here to see the statistics on "Nature Medicine" .
References (41)
    Cited by 2 articles
      Back to Top Top