Enriched power of disease-concordant twin-case-only design in detecting interactions in genome-wide association studies

Weilong Li, Jan Baumbach, Afsaneh Mohammadnejad, Charlotte Brasch-Andersen, Fabio Vandin, Jan O. Korbel, Qihua Tan*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

6 Downloads (Pure)

Abstract

Genetic interaction is a crucial issue in the understanding of functional pathways underlying complex diseases. However, detecting such interaction effects is challenging in terms of both methodology and statistical power. We address this issue by introducing a disease-concordant twin-case-only design, which applies to both monozygotic and dizygotic twins. To investigate the power, we conducted a computer simulation study by setting a series of parameter schemes with different minor allele frequencies and relative risks. Results from the simulation study reveals that the disease-concordant twin-case-only design largely reduces sample size required for sufficient power compared to the ordinary case-only design for detecting gene-gene interaction using unrelated individuals. Sample sizes for dizygotic and monozygotic twins were roughly 1/2 and 1/4 of sample sizes in the ordinary case-only design. Since dizygotic twins are genetically similar as siblings, the enriched power for dizygotic twins also applies to affected siblings, which could help to largely extend the application of the powerful twin-case-only design. In summary, our simulation reveals high value of disease-concordant twins and siblings in efficiently detecting gene-by-gene interactions.
Original languageEnglish
JournalEuropean Journal of Human Genetics
Volume27
Issue number4
Pages (from-to)631-636
ISSN1018-4813
DOIs
Publication statusPublished - 1. Apr 2019

Fingerprint

Dizygotic Twins
Genome-Wide Association Study
Sample Size
Siblings
Monozygotic Twins
Computer Simulation
Power (Psychology)

Cite this

@article{346b23abf55d41f79736337f7701f0d8,
title = "Enriched power of disease-concordant twin-case-only design in detecting interactions in genome-wide association studies",
abstract = "Genetic interaction is a crucial issue in the understanding of functional pathways underlying complex diseases. However, detecting such interaction effects is challenging in terms of both methodology and statistical power. We address this issue by introducing a disease-concordant twin-case-only design, which applies to both monozygotic and dizygotic twins. To investigate the power, we conducted a computer simulation study by setting a series of parameter schemes with different minor allele frequencies and relative risks. Results from the simulation study reveals that the disease-concordant twin-case-only design largely reduces sample size required for sufficient power compared to the ordinary case-only design for detecting gene-gene interaction using unrelated individuals. Sample sizes for dizygotic and monozygotic twins were roughly 1/2 and 1/4 of sample sizes in the ordinary case-only design. Since dizygotic twins are genetically similar as siblings, the enriched power for dizygotic twins also applies to affected siblings, which could help to largely extend the application of the powerful twin-case-only design. In summary, our simulation reveals high value of disease-concordant twins and siblings in efficiently detecting gene-by-gene interactions.",
author = "Weilong Li and Jan Baumbach and Afsaneh Mohammadnejad and Charlotte Brasch-Andersen and Fabio Vandin and Korbel, {Jan O.} and Qihua Tan",
year = "2019",
month = "4",
day = "1",
doi = "10.1038/s41431-018-0320-2",
language = "English",
volume = "27",
pages = "631--636",
journal = "European Journal of Human Genetics",
issn = "1018-4813",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Enriched power of disease-concordant twin-case-only design in detecting interactions in genome-wide association studies

AU - Li, Weilong

AU - Baumbach, Jan

AU - Mohammadnejad, Afsaneh

AU - Brasch-Andersen, Charlotte

AU - Vandin, Fabio

AU - Korbel, Jan O.

AU - Tan, Qihua

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Genetic interaction is a crucial issue in the understanding of functional pathways underlying complex diseases. However, detecting such interaction effects is challenging in terms of both methodology and statistical power. We address this issue by introducing a disease-concordant twin-case-only design, which applies to both monozygotic and dizygotic twins. To investigate the power, we conducted a computer simulation study by setting a series of parameter schemes with different minor allele frequencies and relative risks. Results from the simulation study reveals that the disease-concordant twin-case-only design largely reduces sample size required for sufficient power compared to the ordinary case-only design for detecting gene-gene interaction using unrelated individuals. Sample sizes for dizygotic and monozygotic twins were roughly 1/2 and 1/4 of sample sizes in the ordinary case-only design. Since dizygotic twins are genetically similar as siblings, the enriched power for dizygotic twins also applies to affected siblings, which could help to largely extend the application of the powerful twin-case-only design. In summary, our simulation reveals high value of disease-concordant twins and siblings in efficiently detecting gene-by-gene interactions.

AB - Genetic interaction is a crucial issue in the understanding of functional pathways underlying complex diseases. However, detecting such interaction effects is challenging in terms of both methodology and statistical power. We address this issue by introducing a disease-concordant twin-case-only design, which applies to both monozygotic and dizygotic twins. To investigate the power, we conducted a computer simulation study by setting a series of parameter schemes with different minor allele frequencies and relative risks. Results from the simulation study reveals that the disease-concordant twin-case-only design largely reduces sample size required for sufficient power compared to the ordinary case-only design for detecting gene-gene interaction using unrelated individuals. Sample sizes for dizygotic and monozygotic twins were roughly 1/2 and 1/4 of sample sizes in the ordinary case-only design. Since dizygotic twins are genetically similar as siblings, the enriched power for dizygotic twins also applies to affected siblings, which could help to largely extend the application of the powerful twin-case-only design. In summary, our simulation reveals high value of disease-concordant twins and siblings in efficiently detecting gene-by-gene interactions.

UR - https://www.ncbi.nlm.nih.gov/pubmed/30659261

U2 - 10.1038/s41431-018-0320-2

DO - 10.1038/s41431-018-0320-2

M3 - Journal article

VL - 27

SP - 631

EP - 636

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1018-4813

IS - 4

ER -