A comparison of popular TDT-generalizations for family-based association analysis.
Hardy-Weinberg equilibrium
TDT
Type 1 error
family-based association test
population admixture
Journal
Genetic epidemiology
ISSN: 1098-2272
Titre abrégé: Genet Epidemiol
Pays: United States
ID NLM: 8411723
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
12
06
2018
revised:
26
09
2018
accepted:
26
11
2018
pubmed:
5
1
2019
medline:
11
5
2019
entrez:
5
1
2019
Statut:
ppublish
Résumé
The transmission disequilibrium test (TDT) is the gold standard for testing the association between a genetic variant and disease in samples consisting of affected individuals and their parents. In practice, more complex pedigree structures, that is siblings with no parents, or three-generational pedigrees with possibly missing genotypes, are common. There are several generalizations of the TDT that are suitable for use with arbitrary pedigree structures. We consider three such frequently used generalizations, family-based association test, pedigree disequilibrium test, and generalized disequilibrium test, that have accompanying software and compare them regarding validity and power in the single variant setting. We use simulations to study the effects of population admixture, populations whose genotypes are not in Hardy-Weinberg equilibrium (HWE), different pedigree structures, and the presence of linkage. Whereas our results show that some TDT generalizations can have a substantially increased Type 1 error, these tests are often used in substantive research without caveats about the validity of their Type 1 error. For the association analysis of rare variants in sequencing studies, region-based extensions of the TDT generalizations, that rely on the postulated robustness of the single variant tests, have been proposed. We discuss the implications of our results for these region-based extensions.
Identifiants
pubmed: 30609057
doi: 10.1002/gepi.22181
pmc: PMC6599182
mid: NIHMS1003938
doi:
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
300-317Subventions
Organisme : NHLBI NIH HHS
ID : U01HL089897
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01HL132825
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01HG008976
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01HL089856
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL089897
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL089856
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL120839
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01HL120839
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG008976
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL132825
Pays : United States
Informations de copyright
© 2019 Wiley Periodicals, Inc.
Références
Am J Hum Genet. 1999 Mar;64(3):861-70
pubmed: 10053021
Am J Epidemiol. 1999 Jul 1;150(1):97-104
pubmed: 10400559
Hum Hered. 2000 Jul-Aug;50(4):211-23
pubmed: 10782012
Am J Hum Genet. 2000 Jul;67(1):146-54
pubmed: 10825280
Am J Hum Genet. 2000 Dec;67(6):1515-25
pubmed: 11058432
Am J Hum Genet. 2001 Apr;68(4):1065-7
pubmed: 11254459
Biometrics. 1999 Dec;55(4):997-1004
pubmed: 11315092
Biostatistics. 2003 Apr;4(2):195-206
pubmed: 12925516
Genet Epidemiol. 2004 Jan;26(1):61-9
pubmed: 14691957
Stat Med. 2004 Jan 30;23(2):179-89
pubmed: 14716720
Nat Rev Genet. 2006 May;7(5):385-94
pubmed: 16619052
Am J Hum Genet. 2009 Sep;85(3):364-76
pubmed: 19732865
Nat Methods. 2011 Sep 04;8(10):833-5
pubmed: 21892150
Nat Genet. 2012 Jun 17;44(7):821-4
pubmed: 22706312
PLoS One. 2013;8(1):e48495
pubmed: 23341868
Am J Hum Genet. 2014 Jan 2;94(1):33-46
pubmed: 24360806
Bioinformatics. 2015 May 1;31(9):1452-9
pubmed: 25568282
Nat Genet. 2015 Mar;47(3):284-90
pubmed: 25642633
Am J Hum Genet. 2015 May 7;96(5):720-30
pubmed: 25892111
Am J Hum Genet. 2016 Apr 7;98(4):653-66
pubmed: 27018471
Am J Hum Genet. 2017 Jan 5;100(1):31-39
pubmed: 28017371
Am J Hum Genet. 2017 Feb 2;100(2):193-204
pubmed: 28065470
Genet Epidemiol. 2018 Feb;42(1):123-126
pubmed: 29159827
Nat Genet. 2018 Sep;50(9):1335-1341
pubmed: 30104761
Mol Psychiatry. 2018 Aug 16;:null
pubmed: 30116028
Genetica. 1995;96(1-2):3-12
pubmed: 7607457
Am J Hum Genet. 1995 Aug;57(2):455-64
pubmed: 7668272
Am J Hum Genet. 1993 Mar;52(3):506-16
pubmed: 8447318
Am J Hum Genet. 1998 Feb;62(2):450-8
pubmed: 9463321