Dataset Information

Selection of the most informative individuals from families with multiple siblings for association studies.

ABSTRACT: Association analyses may follow an initial linkage analysis for mapping and identifying genes underlying complex quantitative traits and may be conducted on unrelated subsets of individuals where only one member of a family is included. We evaluate two methods to select one sibling per sibship when multiple siblings are available: (1) one sibling with the most extreme trait value; and (2) one sibling using a combination score statistic based on extreme trait values and identity-by-descent sharing information. We compare the type I error and power. Furthermore, we compare these selection strategies with a strategy that randomly selects one sibling per sibship and with an approach that includes all siblings, using both simulation study and an application to fasting blood glucose in the Framingham Heart Study. When genetic effect is homogeneous, we find that using the combination score can increase power by 30-40% compared to a random selection strategy, and loses only 8-13% of power compared to the full sibship analysis, across all additive models considered, but offers at least 50% genotyping cost saving. In the presence of genetic heterogeneity, the score offers a 50% increase in power over a random selection strategy, but there is substantial loss compared to the full sibship analysis. In application to fasting blood sample, two SNPs are found in common for the selection strategies and the full sample among the 10 highest ranked single nucleotide polymorphisms. The EV strategy tends to agree with the IBD-EV strategy and the analysis of the full sample.

SUBMITTER: Liu C

PROVIDER: S-EPMC3747668 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Selection of the most informative individuals from families with multiple siblings for association studies.

Liu Chunyu C Yang Qiong Q Adrienne Cupples L L Meigs James B JB Dupuis Josée J

Genetic epidemiology 20090501 4

Association analyses may follow an initial linkage analysis for mapping and identifying genes underlying complex quantitative traits and may be conducted on unrelated subsets of individuals where only one member of a family is included. We evaluate two methods to select one sibling per sibship when multiple siblings are available: (1) one sibling with the most extreme trait value; and (2) one sibling using a combination score statistic based on extreme trait values and identity-by-descent sharin ...[more]

PMID: 19025786

Similar Datasets

Project description:ObjectiveThis study evaluated factors influencing reproductive decision-making in families containing multiple individuals with epilepsy.MethodsOne hundred forty-nine adults with epilepsy and 149 adult biological relatives without epilepsy from families containing multiple affected individuals completed a self-administered questionnaire. Participants answered questions regarding their belief in a genetic cause of epilepsy (genetic attribution) and estimated risk of epilepsy in offspring of an affected person. Participants rated factors for their influence on their reproductive plans, with responses ranging from "much more likely" to "much less likely" to want to have a child. Those with epilepsy were asked, "Do you think you would have wanted more (or any) children if you had not had epilepsy?"ResultsParticipants with epilepsy had fewer offspring than their unaffected relatives (mean = 1.2 vs. 1.9, p = .002), and this difference persisted among persons who had been married. Estimates of risk of epilepsy in offspring of an affected parent were higher among participants with epilepsy than among relatives without epilepsy (mean = 27.2 vs. 19.6, p = .002). Nineteen percent of participants with epilepsy responded that they would have wanted more children if they had not had epilepsy. Twenty-five percent of participants with epilepsy responded that "the chance of having a child with epilepsy" or "having epilepsy in your family" made them less likely to want to have a child. Having these genetic concerns was significantly associated with greater genetic attribution and estimated risk of epilepsy in offspring of an affected parent.SignificancePeople with epilepsy have fewer children than their biological relatives without epilepsy. Beliefs about genetic causes of epilepsy contribute to concerns and decisions to limit childbearing. These beliefs should be addressed in genetic counseling to ensure that true risks to offspring and reproductive options are well understood.

Dataset Information

Selection of the most informative individuals from families with multiple siblings for association studies.

Publications

Selection of the most informative individuals from families with multiple siblings for association studies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets