Document Detail


Polygenic heritability estimates in pharmacogenetics: focus on asthma and related phenotypes.
MedLine Citation:
PMID:  23532052     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although accurate measures of heritability are required to understand the pharmacogenetic basis of drug treatment response, these are generally not available, as it is unfeasible to give medications to individuals for which treatment is not indicated. Using a polygenic linear mixed modeling approach, we estimated lower bounds on the heritability of asthma and the heritability of two related drug-response phenotypes, bronchodilator response and airway hyperreactivity, using genome-wide single nucleotide polymorphism (SNP) data from existing asthma cohorts. Our estimate of the heritability for bronchodilator response is 28.5% (SE 16%, P=0.043) and airway hyperresponsiveness is 51.1% (SE 34%, P=0.064), whereas we estimate asthma genetic liability at 61.5% (SE 16%, P<0.001). Our results agree with the previously published estimates of the heritability of these traits, suggesting that the linear mixed modeling method is useful for computing the heritability of other pharmacogenetic traits. Furthermore, our results indicate that multiple SNP main effects, including SNPs as yet unidentified by genome-wide association study methods, together explain a sizable portion of the heritability of these traits.
Authors:
Michael J McGeachie; Eli A Stahl; Blanca E Himes; Sarah A Pendergrass; John J Lima; Charles G Irvin; Stephen P Peters; Marylyn D Ritchie; Robert M Plenge; Kelan G Tantisira
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pharmacogenetics and genomics     Volume:  23     ISSN:  1744-6880     ISO Abbreviation:  Pharmacogenet. Genomics     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-04-25     Completed Date:  2014-01-10     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  101231005     Medline TA:  Pharmacogenet Genomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  324-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Asthma / drug therapy,  genetics*,  physiopathology
Bronchial Hyperreactivity / drug therapy,  genetics,  physiopathology
Bronchodilator Agents / therapeutic use
Clinical Trials as Topic
Genetic Predisposition to Disease*
Humans
Multifactorial Inheritance / genetics*
Pharmacogenetics*
Phenotype
Polymorphism, Single Nucleotide / genetics
Grant Support
ID/Acronym/Agency:
K12 HL089990/HL/NHLBI NIH HHS; K99 HL105663/HL/NHLBI NIH HHS; K99 HL105663/HL/NHLBI NIH HHS; P01 HL083069/HL/NHLBI NIH HHS; R00 HL105663/HL/NHLBI NIH HHS; R01 HL086601/HL/NHLBI NIH HHS; R01 HL090197/HL/NHLBI NIH HHS; R01 NR013391/NR/NINR NIH HHS; R01 NR013391/NR/NINR NIH HHS; T32 HL07427/HL/NHLBI NIH HHS; U01 HL065899/HL/NHLBI NIH HHS; U01 HL065899/HL/NHLBI NIH HHS; U01 HL075419/HL/NHLBI NIH HHS; U01 HL075419/HL/NHLBI NIH HHS; U19 HL065926/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Bronchodilator Agents
Comments/Corrections

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