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@ARTICLE{Park:138071,
author = {Park, Suyeon and Lee, Sungyoung and Lee, Young and Herold,
Christine and Hooli, Basavaraj and Mullin, Kristina and
Park, Taesung and Park, Changsoon and Bertram, Lars and
Lange, Christoph and Tanzi, Rudolph and Won, Sungho},
title = {{A}djusting heterogeneous ascertainment bias for genetic
association analysis with extended families.},
journal = {BMC medical genetics},
volume = {16},
number = {1},
issn = {1471-2350},
address = {Heidelberg},
publisher = {Springer},
reportid = {DZNE-2020-04393},
pages = {62},
year = {2015},
abstract = {In family-based association analysis, each family is
typically ascertained from a single proband, which renders
the effects of ascertainment bias heterogeneous among family
members. This is contrary to case-control studies, and may
introduce sample or ascertainment bias. Statistical
efficiency is affected by ascertainment bias, and careful
adjustment can lead to substantial improvements in
statistical power. However, genetic association analysis has
often been conducted using family-based designs, without
addressing the fact that each proband in a family has had a
great influence on the probability for each family member to
be affected.We propose a powerful and efficient statistic
for genetic association analysis that considered the
heterogeneity of ascertainment bias among family members,
under the assumption that both prevalence and heritability
of disease are available. With extensive simulation studies,
we showed that the proposed method performed better than the
existing methods, particularly for diseases with large
heritability.We applied the proposed method to the
genome-wide association analysis of Alzheimer's disease.
Four significant associations with the proposed method were
found.Our significant findings illustrated the practical
importance of this new analysis method.},
keywords = {Alzheimer Disease: genetics / Computer Simulation / Data
Interpretation, Statistical / Family / Gene Frequency /
Genetic Association Studies: methods / Genetic Heterogeneity
/ Humans / Selection Bias},
cin = {GenomMathematik / U T4 Researchers - Bonn},
ddc = {610},
cid = {I:(DE-2719)1013007 / I:(DE-2719)7000008},
pnm = {345 - Population Studies and Genetics (POF3-345)},
pid = {G:(DE-HGF)POF3-345},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26286599},
pmc = {pmc:PMC4593209},
doi = {10.1186/s12881-015-0198-6},
url = {https://pub.dzne.de/record/138071},
}