Population-based identity-by-descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia.

American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics
Denise HaroldDerek W Morris

Abstract

Genome-wide association studies (GWASs) are highly effective at identifying common risk variants for schizophrenia. Rare risk variants are also important contributors to schizophrenia etiology but, with the exception of large copy number variants, are difficult to detect with GWAS. Exome and genome sequencing, which have accelerated the study of rare variants, are expensive so alternative methods are needed to aid detection of rare variants. Here we re-analyze an Irish schizophrenia GWAS dataset (n = 3,473) by performing identity-by-descent (IBD) mapping followed by exome sequencing of individuals identified as sharing risk haplotypes to search for rare risk variants in coding regions. We identified 45 rare haplotypes (>1 cM) that were significantly more common in cases than controls. By exome sequencing 105 haplotype carriers, we investigated these haplotypes for functional coding variants that could be tested for association in independent GWAS samples. We identified one rare missense variant in PCNT but did not find statistical support for an association with schizophrenia in a replication analysis. However, IBD mapping can prioritize both individual samples and genomic regions for follow-up analysis but genome rather than e...Continue Reading

References

Jul 1, 1978·Archives of General Psychiatry·J Endicott, R L Spitzer
Jun 8, 2007·Nature·UNKNOWN Wellcome Trust Case Control Consortium
Jul 16, 2008·Science·Eric M MorrowChristopher A Walsh
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
May 7, 2010·The New England Journal of Medicine·A Gulhan Ercan-SencicekMatthew W State
Apr 16, 2011·Bioinformatics·Derek W BarnettGabor T Marth
Jun 10, 2011·Bioinformatics·Petr DanecekUNKNOWN 1000 Genomes Project Analysis Group
Aug 23, 2011·Biological Psychiatry·Elliott ReesGeorge Kirov
Oct 4, 2011·Cell·James R LupskiRichard A Gibbs
Dec 6, 2011·Nature Methods·Olivier DelaneauJean-François Zagury
Jan 24, 2012·Genetics·Sharon R Browning, Elizabeth A Thompson
May 26, 2012·Nature Neuroscience·Maria KarayiorgouUNKNOWN Genetic and Neural Complexity in Psychiatry 2011 Working Group
Aug 14, 2012·Biological Psychiatry·UNKNOWN Irish Schizophrenia Genomics Consortium and the Wellcome Trust Case Control Consortium 2
Feb 21, 2013·Trends in Genetics : TIG·Liping HouFrancis J McMahon
Dec 24, 2013·Bioinformatics·Yu QianSharon R Browning
Jan 28, 2014·Nature·Menachem FromerMichael C O'Donovan
Jan 28, 2014·Nature·Shaun M PurcellPamela Sklar
Jul 25, 2014·Nature·UNKNOWN Schizophrenia Working Group of the Psychiatric Genomics Consortium
Aug 28, 2014·European Journal of Human Genetics : EJHG·Helga WesterlindJan Hillert
Jan 8, 2016·Human Molecular Genetics·A L RichardsM C O'Donovan
Oct 28, 2016·Nature Neuroscience·Giulio GenoveseSteven A McCarroll
Nov 22, 2016·Nature Genetics·Christian R MarshallUNKNOWN CNV and Schizophrenia Working Groups of the Psychiatric Genomics Consortium

❮ Previous
Next ❯

Citations

Jul 16, 2021·Genome Medicine·Kar-Tong TanAndrew L Hong

❮ 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.