Abstract：
:The recent progress in sequencing technologies makes possible large-scale medical sequencing efforts to assess the importance of rare variants in complex diseases. The results of such efforts depend heavily on the use of efficient study designs and analytical methods. We introduce here a unified framework for association testing of rare variants in family-based designs or designs based on unselected affected individuals. This framework allows us to quantify the enrichment in rare disease variants in families containing multiple affected individuals and to investigate the optimal design of studies aiming to identify rare disease variants in complex traits. We show that for many complex diseases with small values for the overall sibling recurrence risk ratio, such as Alzheimer's disease and most cancers, sequencing affected individuals with a positive family history of the disease can be extremely advantageous for identifying rare disease variants. In contrast, for complex diseases with large values of the sibling recurrence risk ratio, sequencing unselected affected individuals may be preferable.
journal_name
Geneticsjournal_title
Geneticsauthors
Ionita-Laza I,Ottman Rdoi
10.1534/genetics.111.131813subject
Has Abstractpub_date
2011-11-01 00:00:00pages
1061-8issue
3eissn
0016-6731issn
1943-2631pii
genetics.111.131813journal_volume
189pub_type
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