Improving the robustness of the weighted pairwise correlation test for linkage analysis

Genetic Epidemiology
D Commenges, Laurent Abel

Abstract

The weighted pairwise correlation (WPC) approach provides simple and flexible tests for genetic linkage which may be adapted to qualitative, quantitative, or age-dependent traits. These tests also seem to have good power. However, when working with large pedigrees, a disease susceptibility gene not linked to the marker studied induces correlations of the trait values, leading to inflated type-I errors for these tests. Thus, in its first version, the WPC approach is reliable when using sibships but not when using larger pedigrees. We propose a way for correcting the variances of the WPC statistics to take these correlations into account. A simulation study shows that the type I errors of the corrected statistics are good. The approach is based on a transformation which yields uncorrelated residuals. We study three statistics, based on the permutation distributions of residuals: one based on ordinary residuals adapted to quantitative traits, another based on martingale residuals adapted to survival data, and one based on rank residuals which can be used in both situations. We apply the corrected WPC tests to pedigrees of Alzheimer's disease previously analyzed with the first version of the method (WRPC).

References

Jan 1, 1991·Journal of Clinical Epidemiology·A Donner, M Eliasziw
Jan 1, 1995·Genetic Epidemiology·M C SpeerJ Ott
Jan 1, 1995·Lifetime Data Analysis·D Commenges, P K Andersen

❮ Previous
Next ❯

Citations

Aug 24, 1999·European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics·A N AbdallahA Iron
Apr 20, 2005·Human Heredity·L BeckmannJ Chang-Claude
Sep 17, 2002·Biometrics·Chang Yu, Daniel Zelterman
Aug 21, 2003·Biometrics·David TritchlerShafagh Fallah
Jan 1, 1997·Genetic Epidemiology·D Commenges, M Beurton-Aimar
Jun 16, 2000·Journal of the National Cancer Institute. Monographs·D J SchaidC Dahl
May 2, 2001·Statistical Methods in Medical Research·M C Shih, A S Whittemore
May 2, 2001·Statistical Methods in Medical Research·C I Amos, M de Andrade
Apr 30, 2009·Statistics in Medicine·A CallegaroJ J Houwing-Duistermaat

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.