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PMID: 23386037 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Family-based association tests for sequence data, and comparisons with population-based association tests.

European journal of human genetics : EJHG ·Vol. 21 ·No. 10 ·2013-10-00 ·Pages 1158-62

Ionita-Laza I, Lee S, Makarov V, Buxbaum JD, Lin X

Abstract

Recent advances in high-throughput sequencing technologies make it increasingly more efficient to sequence large cohorts for many complex traits. We discuss here a class of sequence-based association tests for family-based designs that corresponds naturally to previously proposed population-based tests, including the classical Burden and variance-component tests. This framework allows for a direct comparison between the powers of sequence-based association tests with family- vs population-based designs. We show that for dichotomous traits using family-based controls results in similar power levels as the population-based design (although at an increased sequencing cost for the family-based design), while for continuous traits (in random samples, no ascertainment) the population-based design can be substantially more powerful. A possible disadvantage of population-based designs is that they can lead to increased false-positive rates in the presence of population stratification, while the family-based designs are robust to population stratification. We show also an application to a small exome-sequencing family-based study on autism spectrum disorders. The tests are implemented in publicly available software.

MeSH Terms
Child Development Disorders, Pervasive/genetics Exome Genetic Association Studies/methods Humans Pedigree Population/genetics Sensitivity and Specificity Sequence Analysis, DNA/methods Software
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Ionita-Laza Iuliana
Department of Biostatistics, Columbia University, New York, NY, USA.
Lee Seunggeun
Makarov Vladimir
Buxbaum Joseph D
Lin Xihong
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Article Info
Journal
European journal of human genetics : EJHG
Abbr.
Eur J Hum Genet
ISSN
1476-5438
DOI
10.1038/ejhg.2012.308
Published
2013-10-00
Epub
2013-00-06
Pages
1158-62
Language
English
Region
England
NLM ID
9302235
PMCID
PMC3778346
Subset
IM
Grants
NHGRI NIH HHS · R03 HG005908 · United States
NCI NIH HHS · R35 CA197449 · United States
NCI NIH HHS · R37 CA076404 · United States
NIMH NIH HHS · MH089025 · United States
NIMH NIH HHS · R01MH095797 · United States
NHGRI NIH HHS · 1R03HG005908 · United States
NIMH NIH HHS · R01 MH089025 · United States
NCI NIH HHS · P01CA134294 · United States
NIMH NIH HHS · R01 MH095797 · United States
NHLBI NIH HHS · K99 HL113164 · United States
NCI NIH HHS · P01 CA134294 · United States
External Links
PubMed source DOI: 10.1038/ejhg.2012.308 PMC Full Text View journal details
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