Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
17372818
TITLE
Ascertainment through family history of disease often decreases the power of family-based association studies.
ABSTRACT
Selection of cases with additional affected relatives has been shown to increase the power of the case-control association design. We investigated whether this strategy can also improve the power of family-based association studies that use the transmission disequilibrium test (TDT), while accounting for the effects of residual polygenic and environmental factors on disease liability. Ascertainment of parent-offspring trios conditional on the proband having affected first-degree relatives almost always reduced the power of the TDT. For many disease models, this reduction was quite considerable. In contrast, for the same sample size, designs that analyzed more than one affected offspring per family often improved power when compared to the standard parent-offspring trio design. Together, our results suggest that (1) residual polygenic and environmental influences should be considered when estimating the power of the TDT for studies that ascertain families with multiple affected relatives; (2) if trios are selected conditional on having additional affected offspring, then it is important to genotype and include in the analysis the additional siblings; (3) the ascertainment strategy should be considered when interpreting results from TDT analyses. Our analytic approach to estimate the asymptotic power of the TDT is implemented online at http://pngu.mgh.harvard.edu/ ~purcell/gpc/.
DATE PUBLISHED
2007 Jul
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2006/09/08
accepted 2007/02/15
aheadofprint 2007/03/20
pubmed 2007/03/21 09:00
medline 2007/10/05 09:00
entrez 2007/03/21 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Ferreira MA Ferreira Manuel A R MA Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge St, Boston, MA 02114, USA. mferreira@chgr.mgh.harvard.edu
Sham P Sham Pak P
Daly MJ Daly Mark J MJ
Purcell S Purcell Shaun S
INVESTIGATORS
JOURNAL
VOLUME: 37
ISSUE: 4
TITLE: Behavior genetics
ISOABBREVIATION: Behav. Genet.
YEAR: 2007
MONTH: Jul
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0001-8244
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Behav Genet
COUNTRY: United States
ISSNLINKING: 0001-8244
NLMUNIQUEID: 0251711
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
EY-12562 NEI NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Child
Disease
Female
Humans
Linkage Disequilibrium
Male
Medical History Taking
Models, Genetic
Nuclear Family
Pedigree
Prevalence
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's