General Principles of Endocrine Genetics

Abstract

Like every human phenotype, endocrine disorders depend on interactions of the individual's genetic constitution with environmental factors. The relative contribution of genetics varies, ranging from dysfunction of the endocrine system caused by mutation in a single gene and inherited in a recognizable pattern (monogenic or Mendelian diseases) to multifactorial endocrine phenotypes to whose etiology multiple genetic loci contribute without any one being either necessary or sufficient, in interaction with environmental factors (complex traits). The genetic variants involved may be rare or common and may represent loss or gain of function. Discovery of the genes involved and, especially, of the mechanism by which their variants influence the function of the endocrine system holds high promise to advance understanding of the disease involved and lead to therapeutic advances. Recent progress in genetic methodology is leading to the discovery of the genes involved in increasingly rare monogenic endocrinopathies as well as in increasingly complex genetic architectures of common and rare variants influencing complex endocrine phenotypes.