Analysing the effect of candidate genes on complex traits: an application in multiple sclerosis.

Immunogenetics
Tineke Hooper-van VeenBernard M J Uitdehaag

Abstract

The conventional approach of candidate gene studies in complex diseases is to look at the effect of one gene at a time. However, as the outcome of chronic diseases is influenced by a large number of alleles, simultaneous analysis is needed. We demonstrate the application of multivariate regression and cluster analysis to a multiple sclerosis (MS) dataset with genotypes for 489 patients at 11 candidate genes selected on their involvement in the immune response. Using multivariate regression, we observed that different sets of genes were associated with different disease characteristics that reflect different aspects of disease. Out of 15 polymorphisms, we identified one that contributed to the severity of disease. In addition, the set of 15 polymorphisms was predictive for yearly increase in lesion volume as seen on T1-weighted MRI (p=0.044). From this set, no individual polymorphisms could be identified after adjustment for multiple hypotheses testing. By means of a cluster analysis, we aimed to identify subgroups of patients with different pathogenic subtypes of MS on the basis of their genetic profile. We constructed genetic profiles from the genotypes at the 11 candidate genes. The approach proved to be feasible. We observed...Continue Reading

References

Mar 1, 1983·Annals of Neurology·C M PoserW W Tourtellotte
Aug 1, 1994·Brain : a Journal of Neurology·T ReveszW I McDonald
Dec 1, 1996·Brain : a Journal of Neurology·N A LosseffA J Thompson
Apr 29, 1998·Brain : a Journal of Neurology·D H MillerH F McFarland
Dec 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·M B EisenD Botstein
Aug 24, 1999·BMJ : British Medical Journal·D J SpiegelhalterK R Abrams
Feb 24, 2001·Genes and Immunity·M A HallJ S Lanchbury
Jun 19, 2001·American Journal of Human Genetics·J K Pritchard, M Przeworski
Aug 17, 2001·Annals of Neurology·T van VeenB M Uitdehaag
Oct 5, 2001·Nature Genetics·G C JohnsonJ A Todd
Nov 28, 2001·Journal of Neurology, Neurosurgery, and Psychiatry·J ChatawayA Compston
Mar 7, 2002·Journal of Neuroimmunology·Orhun H KantarciBrian G Weinshenker
Jul 6, 2002·Journal of Neuroimmunology·T van VeenB M J Uitdehaag
Aug 6, 2002·Journal of Neuroimmunology·C L A MannC P Hawkins
Sep 27, 2002·Annals of Neurology·Iraide AllozaKoen Vandenbroeck
Jul 17, 2003·Journal of Neuroimmunology·Tineke van VeenBernard M J Uitdehaag
Aug 7, 2003·Journal of Neuropathology and Experimental Neurology·Lars BøSverre J Mørk
Nov 12, 2003·Neurology·T van VeenB M J Uitdehaag
Dec 4, 2003·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·W Brück, C Stadelmann
Dec 11, 2003·Multiple Sclerosis : Clinical and Laboratory Research·Tineke Hooper-van VeenBernard M J Uitdehaag
Jun 9, 2004·European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics·H M SchrijverB M J Uitdehaag

❮ Previous
Next ❯

Citations

Aug 30, 2008·Cellular and Molecular Neurobiology·Mojdeh GhabaeeLeila Hashemi Chelavi
Mar 26, 2011·AJNR. American Journal of Neuroradiology·M H SombekkeH Vrenken
Dec 6, 2014·Neuroimaging Clinics of North America·Stefan Dirk Roosendaal, Frederik Barkhof
Feb 6, 2007·Sleep Medicine·Maninder Kalra, Ranajit Chakraborty
May 11, 2012·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Tineke van VeenFrans G Zitman
Jul 9, 2008·Scandinavian Journal of Urology and Nephrology·Haakon LindekleivJan Due

❮ 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.