Statistical Human Genetics (Methods in Molecular Biology, v850)

578 Pages·2012·11.61 MB·English

by  Robert C. Elston

M M B TM
ETHODS IN OLECULAR IOLOGY
SeriesEditor
JohnM.Walker
School ofLife Sciences
University ofHertfordshire
Hatfield, Hertfordshire,AL109AB,UK
For further volumes:
http://www.springer.com/series/7651
.
Statistical Human Genetics
Methods and Protocols
Edited by
Robert C. Elston
Department of Epidemiology and Biostatistics,
Case Western Reserve University, Cleveland, OH, USA
Jaya M. Satagopan
Department of Epidemiology and Biostatistics,
Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Shuying Sun
Department of Epidemiology and Biostatistics, Case Comprehensive Cancer Center,
Case Western Reserve University, Cleveland, OH, USA
Editors
RobertC.Elston JayaM. Satagopan
DepartmentofEpidemiology Departmentof Epidemiology
andBiostatistics and Biostatistics
CaseWesternReserveUniversity Memorial Sloan-Kettering Cancer Center
Cleveland,OH,USA New York, NY,USA
[email protected] [email protected]
Shuying Sun
Departmentof Epidemiology
and Biostatistics
Case Comprehensive Cancer Center
Case Western Reserve University
Cleveland, OH,USA
[email protected]
ISSN1064-3745 e-ISSN1940-6029
ISBN978-1-61779-554-1 e-ISBN978-1-61779-555-8
DOI10.1007/978-1-61779-555-8
SpringerNewYorkDordrechtHeidelbergLondon
LibraryofCongressControlNumber:2011945439
ªSpringerScience+BusinessMedia,LLC2012
Allrightsreserved.Thisworkmaynotbetranslatedorcopiedinwholeorinpartwithoutthewrittenpermissionofthe
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Preface
Therecentadvancesingenetics,especiallyinthemolecular techniquesthathaveover the
last quarter of a century spectacularly reduced the cost of determining genetic markers,
open up a field of research that is becoming of increasing help in detecting, preventing
and/or curing many diseases that afflict us. This has brought with it the need for novel
methodsofstatisticalanalysisandtheimplementationofthesemethodsinawidevarietyof
computerprograms.Itisouraiminthisbooktomakethesemethodsandprogramsmore
easily accessible to the beginner who has data to analyze, whether a student or a senior
investigator.Apartfromthefirstchapter,whichdefinessomeofthegenetictermsweshall
use, and the last chapter, which compares three major multipurpose programs/software
packages,eachchapterofthisbooktakesupaparticularanalyticaltopicandillustratesthe
use of at least one piece of software that the authors have found helpful for the relevant
statisticalanalysisoftheirownhumangeneticdata.Thereisoftenmorethanoneprogram
that performs a particular type of analysis and, once you have used one program for a
particularanalysis,youmayfindyoupreferanotherprogram—andthereisagoodchance
youwillfindthatthesamebasicanalysisisdescribedinmorethanonechapterofthisbook.
You may therefore wish to browse over several chapters, in the first place restricting your
reading to only the introductory sections, which describe the underlying theory.
Thechaptersareorderedintheapproximatelogicalorderinwhichhumangeneticstudies
are often conducted; so, if you are new to research in human genetics, this initial reading
couldserveas anintroductionto thesubject.Our mainpurpose, however,istoservethe
needsofthosewhohavealreadyperformedtheirstudyandnowneedtoanalyzetheirdata.
The second sections of the chapters give you step-by-step instructions for running the
programs and interpreting the program outputs, with extra notes in the third sections.
However, although ouraimisverymuch to offera “doityourself”manual, therewill be
timeswhenyouwillneedtoconsultastatisticalgeneticist,especiallyfortheinterpretation
ofcomputeroutput.Wehavetriedtobefairlycomprehensiveincoveringstatisticalhuman
genetics,butwedonotcoverhereanyofthebioinformaticsoftwareforgenesequencing,
whichisstillverymuchinitsinfancy.
Cleveland,OH,USA RobertC.Elston
NewYork,NY,USA JayaM.Satagopan
Cleveland,OH,USA ShuyingSun
Cleveland,OH,USA RobertElston
v

Contents
Preface .................................................................... v
Contributors................................................................ ix
1 GeneticTerminology ................................................... 1
RobertC.Elston,JayaM.Satagopan,andShuyingSun
2 IdentificationofGenotypeErrors ........................................ 11
YinY.ShugartandYingWang
3 DetectingPedigreeRelationshipErrors ................................... 25
LeiSun
4 IdentifyingCrypticRelationships......................................... 47
LeiSunandApostolosDimitromanolakis
5 EstimatingAlleleFrequencies............................................ 59
IndraAdriantoandCourtneyMontgomery
6 TestingDeparturefromHardy–WeinbergProportions...................... 77
JianWangandSanjayShete
7 EstimatingDisequilibriumCoefficients.................................... 103
MarenVensandAndreasZiegler
8 DetectingFamilialAggregation .......................................... 119
AdamC.Naj,YoSonPark,andTerriH.Beaty
9 EstimatingHeritabilityfromTwinStudies................................. 151
KarinJ.H.Verweij,MiriamA.Mosing,BrendanP.Zietsch,
andSarahE.Medland
10 EstimatingHeritabilityfromNuclearFamilyandPedigreeData.............. 171
MurielleBochud
11 CorrectingforAscertainment............................................ 187
WarrenEwensandRobertC.Elston
12 SegregationAnalysisUsingtheUnifiedModel............................. 211
XiangqingSun
13 DesignConsiderationsforGeneticLinkageandAssociationStudies.......... 237
Je´re´mieNsengimanaandD.TimothyBishop
14 Model-BasedLinkageAnalysisofaQuantitativeTrait ...................... 263
AudreyH.SchnellandXiangqingSun
15 Model-BasedLinkageAnalysisofaBinaryTrait............................ 285
RitaM.Cantor
16 Model-FreeLinkageAnalysisofaQuantitativeTrait........................ 301
NathanJ.MorrisandCatherineM.Stein
17 Model-FreeLinkageAnalysisofaBinaryTrait............................. 317
WeiXu,ShelleyB.Bull,LuciaMirea,andCeliaM.T.Greenwood
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viii Contents
18 SingleMarkerAssociationAnalysisforUnrelatedSamples................... 347
GangZheng,JinfengXu,AoYuan,andJosephL.Gastwirth
19 Single-MarkerFamily-BasedAssociationAnalysisConditional
onParentalInformation ................................................ 359
Ren‐HuaChungandEdenR.Martin
20 SingleMarkerFamily-BasedAssociationAnalysisNotConditional
onParentalInformation ................................................ 371
JunghyunNamkung
21 AllowingforPopulationStratificationinAssociationAnalysis................ 399
HuaizhenQinandXiaofengZhu
22 HaplotypeInference.................................................... 411
XinLiandJingLi
23 Multi-SNPHaplotypeAnalysisMethodsforAssociationAnalysis............. 423
DanielO.StramandVenkatramanE.Seshan
24 DetectingRareVariants................................................. 453
TaoFengandXiaofengZhu
25 TheAnalysisofEthnicMixtures.......................................... 465
XiaofengZhu
26 IdentifyingGeneInteractionNetworks ................................... 483
GurkanBebek
27 StructuralEquationModeling ........................................... 495
CatherineM.Stein,NathanJ.Morris,andNoraL.Nock
28 GenotypeCallingfor theAffymetrixPlatform ............................. 513
ArneSchillertandAndreasZiegler
29 GenotypeCallingfor theIlluminaPlatform ............................... 525
YikYingTeo
30 ComparisonofRequirementsandCapabilitiesofMajor
MultipurposeSoftwarePackages ......................................... 539
RobertP.IgoJr.andAudreyH.Schnell
Index...................................................................... 559
Contributors
INDRA ADRIANTO (cid:1) Arthritis and Clinical Immunology Research Program,
Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
TERRI H. BEATY (cid:1) Department of Epidemiology, Johns Hopkins Bloomberg
School of Public Health, Baltimore, MD, USA
GURKAN BEBEK (cid:1) Center for Proteomics and Bioinformatics, Case Comprehensive
Cancer Center, Case Western Reserve University School of Medicine,
Cleveland, OH, USA
D. TIMOTHY BISHOP (cid:1) Section of Epidemiology and Biostatistics, Leeds Institute
of Molecular Medicine, University of Leeds, Cancer Genetics Building, Leeds, UK
MURIELLE BOCHUD (cid:1) Institute of Social and Preventive Medicine,
University of Lausanne, Lausanne, Switzerland
SHELLEY B. BULL (cid:1) Samuel Lunenfeld Research Institute of Mount Sinai
Hospital and Dalla Lana School of Public Health, University of Toronto,
Toronto, ON, Canada
RITA M. CANTOR (cid:1) Department of Human Genetics, David Geffen School
of Medicine at UCLA, Los Angeles, CA, USA; Center for Neurobehavioral
Genetics, Department of Psychiatry, David Geffen School of Medicine
at UCLA, Los Angeles, CA, USA
REN-HUA CHUNG (cid:1) John P. Hussman Institute for Human Genomics,
Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA
APOSTOLOS DIMITROMANOLAKIS (cid:1) Division of Biostatistics, Dalla Lana School
of Public Health, University of Toronto, Toronto, ON, Canada
ROBERTC. ELSTON (cid:1) Department of Epidemiology and Biostatistics,
Case Western Reserve University, Cleveland, OH, USA
WARREN EWENS (cid:1) Department of Biology, University of Pennsylvania,
Philadelphia, PA, USA
TAO FENG (cid:1) Department of Epidemiology and Biostatistics,
Case Western Reserve University School of Medicine, Cleveland, OH, USA
CELIA M.T. GREENWOOD (cid:1) Centre for Clinical Epidemiology, Lady Davis Research
Institute, Jewish General Hospital, Montreal, QC, Canada;
Cancer Research Society Division of Epidemiology,
Department of Oncology, McGill University, Montreal, QC, Canada
JOSEPH L. GASTWIRTH (cid:1) Department of Statistics, George Washington University,
Washington, DC, USA
ROBERTP. IGO JR (cid:1) Department of Epidemiology and Biostatistics,
Case Western Reserve University, Cleveland, OH, USA
JING LI (cid:1) Department of Electrical Engineering and Computer Science,
Case Western Reserve University, Cleveland, OH, USA
XIN LI (cid:1) Department of Electrical Engineering and Computer Science,
Case Western Reserve University, Cleveland, OH, USA
EDEN R. MARTIN (cid:1) John P. Hussman Institute for Human Genomics,
Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA
ix