Efficient study designs for test of genetic association using sibship data and unrelated cases and controls.

American Journal of Human Genetics
Mingyao LiG R Abecasis

Abstract

Linkage mapping of complex diseases is often followed by association studies between phenotypes and marker genotypes through use of case-control or family-based designs. Given fixed genotyping resources, it is important to know which study designs are the most efficient. To address this problem, we extended the likelihood-based method of Li et al., which assesses whether there is linkage disequilibrium between a disease locus and a SNP, to accommodate sibships of arbitrary size and disease-phenotype configuration. A key advantage of our method is the ability to combine data from different family structures. We consider scenarios for which genotypes are available for unrelated cases, affected sib pairs (ASPs), or only one sibling per ASP. We construct designs that use cases only and others that use unaffected siblings or unrelated unaffected individuals as controls. Different combinations of cases and controls result in seven study designs. We compare the efficiency of these designs when the number of individuals to be genotyped is fixed. Our results suggest that (1) when the disease is influenced by a single gene, the one sibling per ASP-control design is the most efficient, followed by the ASP-control design, and familial case...Continue Reading

References

Apr 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·E S Lander, P Green
Apr 21, 2001·Biometrics·B Devlin, K Roeder
Feb 22, 2002·Theoretical Population Biology·N Risch
Mar 7, 2002·American Journal of Human Genetics·Michael P EpsteinMichael Boehnke
Dec 20, 2003·Nature·UNKNOWN International HapMap Consortium
Jan 31, 2004·American Journal of Human Genetics·Tasha E FingerlinGonçalo R Abecasis
Mar 12, 2005·Science·Jonathan L HainesMargaret A Pericak-Vance
Mar 12, 2005·Science·Albert O EdwardsLindsay A Farrer
Mar 12, 2005·Science·Robert J KleinJosephine Hoh
Apr 19, 2005·American Journal of Human Genetics·Jacqueline K Wittke-ThompsonNancy J Cox
Aug 5, 2005·American Journal of Human Genetics·Johanna JakobsdottirMichael B Gorin
Oct 28, 2005·American Journal of Human Genetics·Demetrius M MaraganoreDennis G Ballinger
Oct 29, 2005·Nature·UNKNOWN International HapMap Consortium

❮ Previous
Next ❯

Citations

Aug 8, 2012·Archives of Neurology·Gyungah JunLindsay A Farrer
Apr 14, 2006·Human Genetics·Carol J EtzelUNKNOWN North American Rheumatoid Arthritis Consortium
Dec 19, 2008·European Journal of Human Genetics : EJHG·Joanna M Biernacka, Heather J Cordell
Sep 22, 2011·European Journal of Human Genetics : EJHG·Tero HiekkalinnaJoseph D Terwilliger
Apr 19, 2012·European Journal of Human Genetics : EJHG·Sebastian Zöllner
Dec 4, 2001·Nature Genetics·Gonçalo R AbecasisLon R Cardon
Jan 10, 2008·European Journal of Human Genetics : EJHG·Peter M VisscherDale R Nyholt
Nov 23, 2007·The New England Journal of Medicine·Sreeram V RamagopalanGeorge C Ebers
Mar 20, 2009·The New England Journal of Medicine·Hiroyuki Morita, Ryozo Nagai
Oct 17, 2008·The New England Journal of Medicine·Emmanuelle BouzigonFlorence Demenais
Sep 18, 2012·Human Molecular Genetics·Ron DoGonçalo R Abecasis
Jan 19, 2011·Annals of Human Genetics·Frank DudbridgeScott G Wilson
Sep 13, 1996·Science·N Risch, K Merikangas
Sep 5, 2008·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Ethan M LangeBao-Li Chang
Nov 17, 2007·BMC Bioinformatics·Karen CurtinNicola J Camp
Jan 16, 2009·BMC Medical Genetics·Tatiana ForoudUNKNOWN Familial Intracranial Aneurysm Study Investigators
Apr 24, 2008·BMC Medical Genetics·Jessica J ConnellySimon G Gregory
May 10, 2008·BMC Proceedings·Pimphen CharoenHeather J Cordell
May 10, 2008·BMC Proceedings·Jun ZhangRichard S Cooper
Oct 31, 2008·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Tuomo RankinenClaude Bouchard
Jun 19, 2008·PloS One·Valérie SirouxUNKNOWN EGEA cooperative group
Jan 2, 2010·Neurosurgical Focus·Matthew C CowperthwaiteMark G Burnett
Mar 25, 2014·Nutrition, Metabolism, and Cardiovascular Diseases : NMCD·S C van DijkN van der Velde
Dec 15, 2015·Journal of Affective Disorders·Emma E M KnowlesDavid C Glahn
Jan 13, 2016·BMC Genomics·Annette M McCoyMolly E McCue

❮ 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.