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Missing heritability of complex diseases: Enlightenment by genetic variants from intermediate phenotypes
Author(s) -
BlancoGómez Adrián,
CastilloLluva Sonia,
del Mar SáezFreire María,
HontecillasPrieto Lourdes,
Mao Jian Hua,
CastellanosMartín Andrés,
PérezLosada Jesus
Publication year - 2016
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.201600084
Subject(s) - heritability , missing heritability problem , phenotype , biology , trait , inheritance (genetic algorithm) , genetics , quantitative trait locus , quantitative genetics , component (thermodynamics) , evolutionary biology , gene , genetic variation , genotype , genetic variants , computer science , physics , programming language , thermodynamics
Diseases of complex origin have a component of quantitative genetics that contributes to their susceptibility and phenotypic variability. However, after several studies, a major part of the genetic component of complex phenotypes has still not been found, a situation known as “missing heritability.” Although there have been many hypotheses put forward to explain the reasons for the missing heritability, its definitive causes remain unknown. Complex diseases are caused by multiple intermediate phenotypes involved in their pathogenesis and, very often, each one of these intermediate phenotypes also has a component of quantitative inheritance. Here we propose that at least part of the missing heritability can be explained by the genetic component of intermediate phenotypes that is not detectable at the level of the main complex trait. At the same time, the identification of the genetic component of intermediate phenotypes provides an opportunity to identify part of the missing heritability of complex diseases.