Finding Rare, Disease-Associated Variants in Isolated Groups: Potential Advantages of Mennonite Populations

Document Type

Article

Authors

Fabiana L. Lopes, Human Genetics Branch, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD
Liping Hou, Human Genetics Branch, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD
Angelica B. W. Boldt, Laboratório de Genética Molecular Humana, Departamento de Genética, Universidade Federal do Paraná, Curitiba, Brazil
Layla Kassem, Human Genetics Branch, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD
Veronica M. Alves, Laboratory of Panic and Respiration, Institute of Psychiatry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Antonio E. Nardi, Laboratory of Panic and Respiration, Institute of Psychiatry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Francis J. McMahon, Human Genetics Branch, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, US Department of Health and Human Services, Bethesda, MDFollow

Open Access Pre-Print

http://digitalcommons.wayne.edu/humbiol_preprints/95/

Abstract

Large-scale genotyping and next-generation sequencing techniques have allowed great advances in the field of molecular genetics. Numerous common variants of low impact have been associated with many complex human traits and diseases, such as bipolar disorder and schizophrenia. Although they may exert a greater impact on risk, few rare disease variants have been found, owing to the greatly increased sample sizes that are typically necessary to demonstrate association with rarer variants. One alternative strategy is to study isolated populations, where historical bottlenecks reduce genetic diversity and some otherwise rare variants may drift to higher frequencies. Here we describe the Mennonite population settlements, considering their history of multiple bottlenecks followed by demographic expansion and a currently widespread geographical distribution. We argue that Mennonite populations are valuable partners for studies seeking genetic variants that exert a high impact on risk for a variety of common disorders, including mental illnesses.

Recommended Citation

Lopes, Fabiana L.; Hou, Liping; Boldt, Angelica B. W.; Kassem, Layla; Alves, Veronica M.; Nardi, Antonio E.; and McMahon, Francis J. (2016) "Finding Rare, Disease-Associated Variants in Isolated Groups: Potential Advantages of Mennonite Populations," Human Biology: Vol. 88: Iss. 2, Article 3.
Available at: https://digitalcommons.wayne.edu/humbiol/vol88/iss2/3