Detecting the dominance component of heritability in isolated and outbred human populations

Anthony F. Herzig, Teresa Nutile, Daniela Ruggiero, Marina Ciullo, Hervé Perdry, Anne Louise Leutenegger

Research output: Contribution to journalArticle

Abstract

Inconsistencies between published estimates of dominance heritability between studies of human genetic isolates and human outbred populations incite investigation into whether such differences result from particular trait architectures or specific population structures. We analyse simulated datasets, characteristic of genetic isolates and of unrelated individuals, before analysing the isolate of Cilento for various commonly studied traits. We show the strengths of using genetic relationship matrices for variance decomposition over identity-by-descent based methods in a population isolate and that heritability estimates in isolates will avoid the downward biases that may occur in studies of samples of unrelated individuals; irrespective of the simulated distribution of causal variants. Yet, we also show that precise estimates of dominance in isolates are demonstrably problematic in the presence of shared environmental effects and such effects should be accounted for. Nevertheless, we demonstrate how studying isolates can help determine the existence or non-existence of dominance for complex traits, and we find strong indications of non-zero dominance for low-density lipoprotein level in Cilento. Finally, we recommend future study designs to analyse trait variance decomposition from ensemble data across multiple population isolates.

Original languageEnglish
Article number18048
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

Fingerprint

Population
Medical Genetics
LDL Lipoproteins
Analysis of Variance
Datasets

ASJC Scopus subject areas

  • General

Cite this

Detecting the dominance component of heritability in isolated and outbred human populations. / Herzig, Anthony F.; Nutile, Teresa; Ruggiero, Daniela; Ciullo, Marina; Perdry, Hervé; Leutenegger, Anne Louise.

In: Scientific Reports, Vol. 8, No. 1, 18048, 01.12.2018.

Research output: Contribution to journalArticle

Herzig, Anthony F. ; Nutile, Teresa ; Ruggiero, Daniela ; Ciullo, Marina ; Perdry, Hervé ; Leutenegger, Anne Louise. / Detecting the dominance component of heritability in isolated and outbred human populations. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
@article{dff8dff232cc457e9cfff3625415fcb0,
title = "Detecting the dominance component of heritability in isolated and outbred human populations",
abstract = "Inconsistencies between published estimates of dominance heritability between studies of human genetic isolates and human outbred populations incite investigation into whether such differences result from particular trait architectures or specific population structures. We analyse simulated datasets, characteristic of genetic isolates and of unrelated individuals, before analysing the isolate of Cilento for various commonly studied traits. We show the strengths of using genetic relationship matrices for variance decomposition over identity-by-descent based methods in a population isolate and that heritability estimates in isolates will avoid the downward biases that may occur in studies of samples of unrelated individuals; irrespective of the simulated distribution of causal variants. Yet, we also show that precise estimates of dominance in isolates are demonstrably problematic in the presence of shared environmental effects and such effects should be accounted for. Nevertheless, we demonstrate how studying isolates can help determine the existence or non-existence of dominance for complex traits, and we find strong indications of non-zero dominance for low-density lipoprotein level in Cilento. Finally, we recommend future study designs to analyse trait variance decomposition from ensemble data across multiple population isolates.",
author = "Herzig, {Anthony F.} and Teresa Nutile and Daniela Ruggiero and Marina Ciullo and Herv{\'e} Perdry and Leutenegger, {Anne Louise}",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41598-018-36050-7",
language = "English",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Detecting the dominance component of heritability in isolated and outbred human populations

AU - Herzig, Anthony F.

AU - Nutile, Teresa

AU - Ruggiero, Daniela

AU - Ciullo, Marina

AU - Perdry, Hervé

AU - Leutenegger, Anne Louise

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Inconsistencies between published estimates of dominance heritability between studies of human genetic isolates and human outbred populations incite investigation into whether such differences result from particular trait architectures or specific population structures. We analyse simulated datasets, characteristic of genetic isolates and of unrelated individuals, before analysing the isolate of Cilento for various commonly studied traits. We show the strengths of using genetic relationship matrices for variance decomposition over identity-by-descent based methods in a population isolate and that heritability estimates in isolates will avoid the downward biases that may occur in studies of samples of unrelated individuals; irrespective of the simulated distribution of causal variants. Yet, we also show that precise estimates of dominance in isolates are demonstrably problematic in the presence of shared environmental effects and such effects should be accounted for. Nevertheless, we demonstrate how studying isolates can help determine the existence or non-existence of dominance for complex traits, and we find strong indications of non-zero dominance for low-density lipoprotein level in Cilento. Finally, we recommend future study designs to analyse trait variance decomposition from ensemble data across multiple population isolates.

AB - Inconsistencies between published estimates of dominance heritability between studies of human genetic isolates and human outbred populations incite investigation into whether such differences result from particular trait architectures or specific population structures. We analyse simulated datasets, characteristic of genetic isolates and of unrelated individuals, before analysing the isolate of Cilento for various commonly studied traits. We show the strengths of using genetic relationship matrices for variance decomposition over identity-by-descent based methods in a population isolate and that heritability estimates in isolates will avoid the downward biases that may occur in studies of samples of unrelated individuals; irrespective of the simulated distribution of causal variants. Yet, we also show that precise estimates of dominance in isolates are demonstrably problematic in the presence of shared environmental effects and such effects should be accounted for. Nevertheless, we demonstrate how studying isolates can help determine the existence or non-existence of dominance for complex traits, and we find strong indications of non-zero dominance for low-density lipoprotein level in Cilento. Finally, we recommend future study designs to analyse trait variance decomposition from ensemble data across multiple population isolates.

UR - http://www.scopus.com/inward/record.url?scp=85058920319&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058920319&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-36050-7

DO - 10.1038/s41598-018-36050-7

M3 - Article

C2 - 30575761

AN - SCOPUS:85058920319

VL - 8

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 18048

ER -