Locus category based analysis of a large genome-wide association study of rheumatoid arthritis.

Human Molecular Genetics
Jan FreudenbergPeter K Gregersen

Abstract

To pinpoint true positive single-nucleotide polymorphism (SNP) associations in a genome-wide association study (GWAS) of rheumatoid arthritis (RA), we categorize genetic loci by external knowledge. We test both the 'enrichment of associated loci' in a locus category and the 'combined association' of a locus category. The former is quantified by the odds ratio for the presence of SNP associations at the loci of a category, whereas the latter is quantified by the number of loci in a category that have SNP associations. These measures are compared with their expected values as obtained from the permutation of the affection status. To account for linkage disequilibrium (LD) among SNPs, we view each LD block as a genetic locus. Positional candidates were defined as loci implicated by earlier GWAS results, whereas functional candidates were defined by annotations regarding the molecular roles of genes, such as gene ontology categories. As expected, immune-related categories show the largest enrichment signal, although it is not very strong. The intersection of positional and functional candidate information predicts novel RA loci near the genes TEC/TXK, MBL2 and PIK3R1/CD180. Notably, a combined association signal is not only produce...Continue Reading

References

Sep 3, 2003·Nature Reviews. Genetics·Josephine Hoh, Jurg Ott
Dec 19, 2003·Nucleic Acids Research·M A HarrisUNKNOWN Gene Ontology Consortium
Dec 19, 2003·Nucleic Acids Research·Evelyn CamonRolf Apweiler
Apr 14, 2004·Genome Research·Ewan BirneyMichele Clamp
Oct 28, 2005·Genome Research·Albert V SmithGonçalo R Abecasis
Jun 8, 2007·Nature·UNKNOWN Wellcome Trust Case Control Consortium
Jun 15, 2007·European Journal of Human Genetics : EJHG·Jan FreudenbergLouis J Ptácek
Jun 19, 2007·PLoS Genetics·Timothy G LesnickDemetrius M Maraganore
Oct 19, 2007·Nature·UNKNOWN International HapMap ConsortiumJohn Stewart
Oct 20, 2007·Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society·Wen FuryWentian Li
Oct 30, 2007·American Journal of Human Genetics·Kai WangMaja Bucan
Jan 9, 2008·The Journal of Experimental Medicine·W K Eddie IpR Alan B Ezekowitz
Aug 30, 2008·Genomics·Ali TorkamaniNicholas J Schork
Sep 17, 2008·Nature Genetics·Soumya RaychaudhuriRobert M Plenge
Sep 17, 2008·Nature Genetics·Anne BartonJane Worthington
Oct 18, 2008·Blood·Satoshi MatsudaShigeo Koyasu
Oct 31, 2008·Genome Research·Alexander GusevItsik Pe'er
Mar 3, 2009·American Journal of Human Genetics·Kai WangHakon Hakonarson
Mar 17, 2009·Human Molecular Genetics·Sergio E BaranziniMichael R Barnes
Apr 1, 2009·Genetic Epidemiology·Kai YuNilanjan Chatterjee
May 29, 2009·Proceedings of the National Academy of Sciences of the United States of America·Lucia A HindorffTeri A Manolio
Jun 23, 2009·American Journal of Human Genetics·Peter HolmansNick Craddock
Jul 3, 2009·Nature·UNKNOWN International Schizophrenia ConsortiumPamela Sklar
Jul 9, 2009·European Journal of Human Genetics : EJHG·Gang PengMomiao Xiong
Jul 22, 2009·Bioinformatics·Colm O'DushlaineAiden Corvin
Nov 26, 2009·BMC Bioinformatics·Apichart IntarapanichSissades Tongsima
Jan 12, 2010·American Journal of Human Genetics·Dina RuanoDanielle Posthuma
Feb 4, 2010·PLoS Biology·Samuel P DicksonDavid B Goldstein

❮ Previous
Next ❯

Citations

Mar 27, 2012·Nature Genetics·Eli A StahlRobert M Plenge
Jun 30, 2009·PMC Biophysics·Yuhong Tan, Ray Luo
Jun 22, 2011·Nature Reviews. Rheumatology·Marina Sirota, Atul J Butte

❮ 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.