Genetic causes of early-onset osteoporosis




Principal Investigator:

Outimaija Mäkitie


Karolinska Institutet

Start Date:


End Date:


Primary Classification:

30107: Medical Genetics


  • Castor /proj at UPPMAX: 29000 GiB
  • Cygnus /proj at UPPMAX: 29000 GiB
  • Castor /proj/nobackup at UPPMAX: 10000 GiB
  • Cygnus /proj/nobackup at UPPMAX: 10000 GiB
  • Bianca at UPPMAX: 2 x 1000 core-h/month


Osteoporosis is characterized by compromised bone strength and increased risk of fractures. Genetic factors play an important role in pathogenesis but the predisposing genes remain largely unknown. This study aims to identify new disease-associated genes and disease-causing gene mutations in patients and families with early-onset osteoporosis. Children, adolescents, adults and families with early-onset primary osteoporosis of unknown cause are recruited from pediatric, endocrine and genetic clinics at Karolinska University Hospital, Stockholm, and through national and international collaborators. All patients undergo careful phenotypic assessment. If family history suggests other affected individuals, the extended family is included. Three separate approaches are used: 1) Candidate-gene approach: Sanger sequencing and MLPA to identify mutations and deletions in recently described osteoporosis-related genes, especially WNT1 and PLS3. 2) Genetic studies in families with multiple affected members: High-resolution oligo-CGH array followed by exome sequencing to search for gene dose imbalances and mutations in the previously identified and novel osteoporosis genes. Discovery of new genes underlying osteoporosis enables development of new diagnostic, preventive and therapeutic methods. Identification of genetic markers that enable presymptomatic diagnosis and prevention of fractures in predisposed individuals will have significant positive human and economic implications. This project was started in 2014 and is still active. Today we currently have about 8 TB of data in our project and we are continuously receiving new data from SciLife and are actively working on this project.