PMID- 36186443
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230612
IS  - 1664-8021 (Print)
IS  - 1664-8021 (Electronic)
IS  - 1664-8021 (Linking)
VI  - 13
DP  - 2022
TI  - Evaluation and characterization of expression quantitative trait analysis methods 
      in the Hybrid Rat Diversity Panel.
PG  - 947423
LID - 10.3389/fgene.2022.947423 [doi]
LID - 947423
AB  - The Hybrid Rat Diversity Panel (HRDP) is a stable and well-characterized set of 
      more than 90 inbred rat strains that can be leveraged for systems genetics 
      approaches to understanding the genetic and genomic variation associated with 
      complex disease. The HRDP exhibits substantial between-strain diversity while 
      retaining substantial within-strain isogenicity, allowing for the precise mapping 
      of genetic variation associated with complex phenotypes and providing statistical 
      power to identify associated variants. In order to robustly identify associated 
      genetic variants, it is important to account for the population structure induced 
      by inbreeding. To this end, we investigate the performance of four plausible 
      approaches towards modeling quantitative traits in the HRDP and quantify their 
      operating characteristics. In particular, we investigate three approaches based 
      on genome-wide mixed model analysis, and one approach based on ordinary least 
      squares linear regression. Towards facilitating study planning and design, we 
      conduct extensive simulations to investigate the power of genetic association 
      analyses in the HRDP, and characterize the impressive attained power. In 
      simulation of eQTL data in the HRDP, we find that a mixed model approach that 
      leverages leave-one-chromosome-out kinship estimation attains the highest power 
      while controlling type I error.
CI  - Copyright (c) 2022 Pattee, Vanderlinden, Mahaffey, Hoffman, Tabakoff and Saba.
FAU - Pattee, Jack
AU  - Pattee J
AD  - Department of Biostatistics and Informatics, Colorado School of Public Health, 
      University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
FAU - Vanderlinden, Lauren A
AU  - Vanderlinden LA
AD  - Department of Epidemiology, Colorado School of Public Health, University of 
      Colorado Anschutz Medical Campus, Aurora, CO, United States.
FAU - Mahaffey, Spencer
AU  - Mahaffey S
AD  - Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and 
      Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, 
      CO, United States.
FAU - Hoffman, Paula
AU  - Hoffman P
AD  - Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and 
      Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, 
      CO, United States.
AD  - Department of Pharmacology, School of Medicine, University of Colorado Anschutz 
      Medical Campus, Aurora, CO, United States.
FAU - Tabakoff, Boris
AU  - Tabakoff B
AD  - Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and 
      Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, 
      CO, United States.
FAU - Saba, Laura M
AU  - Saba LM
AD  - Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and 
      Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, 
      CO, United States.
LA  - eng
GR  - P30 DA044223/DA/NIDA NIH HHS/United States
GR  - R24 AA013162/AA/NIAAA NIH HHS/United States
PT  - Journal Article
DEP - 20220914
PL  - Switzerland
TA  - Front Genet
JT  - Frontiers in genetics
JID - 101560621
PMC - PMC9515987
OTO - NOTNLM
OT  - Hybrid Rat Diversity Panel
OT  - expression quantitative trait loci
OT  - study design
OT  - systems genetics
OT  - transcriptome
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/10/04 06:00
MHDA- 2022/10/04 06:01
PMCR- 2022/09/14
CRDT- 2022/10/03 04:34
PHST- 2022/05/18 00:00 [received]
PHST- 2022/08/26 00:00 [accepted]
PHST- 2022/10/03 04:34 [entrez]
PHST- 2022/10/04 06:00 [pubmed]
PHST- 2022/10/04 06:01 [medline]
PHST- 2022/09/14 00:00 [pmc-release]
AID - 947423 [pii]
AID - 10.3389/fgene.2022.947423 [doi]
PST - epublish
SO  - Front Genet. 2022 Sep 14;13:947423. doi: 10.3389/fgene.2022.947423. eCollection 
      2022.