The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here:

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Leif Groop

Leif Groop

Principal investigator

Leif Groop

Assessing the phenotypic effects in the general population of rare variants in genes for a dominant Mendelian form of diabetes


  • Jason Flannick
  • Nicola L. Beer
  • Alexander G. Bick
  • Vineeta Agarwala
  • Janne Molnes
  • Namrata Gupta
  • Noel P. Burtt
  • Jose C. Florez
  • James B. Meigs
  • Herman Taylor
  • Valeriya Lyssenko
  • Henrik Irgens
  • Ervin Fox
  • Frank Burslem
  • Stefan Johansson
  • M. Julia Brosnan
  • Jeff K. Trimmer
  • Christopher Newton-Cheh
  • Tiinamaija Tuomi
  • Anders Molven
  • James G. Wilson
  • Christopher J. O'Donnell
  • Sekar Kathiresan
  • Joel N. Hirschhorn
  • Pal R. Njolstad
  • Tim Rolph
  • J. G. Seidman
  • Stacey Gabriel
  • David R. Cox
  • Christine E. Seidman
  • Leif Groop
  • David Altshuler

Summary, in English

Genome sequencing can identify individuals in the general population who harbor rare coding variants in genes for Mendelian disorders1-7 and who may consequently have increased disease risk. Previous studies of rare variants in phenotypically extreme individuals display ascertainment bias and may demonstrate inflated effect-size estimates8-12. We sequenced seven genes for maturity-onset diabetes of the young (MODY) 13 in well-phenotyped population samples14,15 (n = 4,003). We filtered rare variants according to two prediction criteria for disease-causing mutations: reported previously in MODY or satisfying stringent de novo thresholds (rare, conserved and protein damaging). Approximately 1.5% and 0.5% of randomly selected individuals from the Framingham and Jackson Heart Studies, respectively, carry variants from these two classes. However, the vast majority of carriers remain euglycemic through middle age. Accurate estimates of variant effect sizes from population-based sequencing are needed to avoid falsely predicting a substantial fraction of individuals as being at risk for MODY or other Mendelian diseases.


  • Genomics, Diabetes and Endocrinology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year







Nature Genetics





Document type

Journal article


Nature Publishing Group


  • Endocrinology and Diabetes



Research group

  • Genomics, Diabetes and Endocrinology


  • ISSN: 1546-1718