Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
23193196
TITLE
Estimation and partitioning of polygenic variation captured by common SNPs for Alzheimer's disease, multiple sclerosis and endometriosis.
ABSTRACT
Common diseases such as endometriosis (ED), Alzheimer's disease (AD) and multiple sclerosis (MS) account for a significant proportion of the health care burden in many countries. Genome-wide association studies (GWASs) for these diseases have identified a number of individual genetic variants contributing to the risk of those diseases. However, the effect size for most variants is small and collectively the known variants explain only a small proportion of the estimated heritability. We used a linear mixed model to fit all single nucleotide polymorphisms (SNPs) simultaneously, and estimated genetic variances on the liability scale using SNPs from GWASs in unrelated individuals for these three diseases. For each of the three diseases, case and control samples were not all genotyped in the same laboratory. We demonstrate that a careful analysis can obtain robust estimates, but also that insufficient quality control (QC) of SNPs can lead to spurious results and that too stringent QC is likely to remove real genetic signals. Our estimates show that common SNPs on commercially available genotyping chips capture significant variation contributing to liability for all three diseases. The estimated proportion of total variation tagged by all SNPs was 0.26 (SE 0.04) for ED, 0.24 (SE 0.03) for AD and 0.30 (SE 0.03) for MS. Further, we partitioned the genetic variance explained into five categories by a minor allele frequency (MAF), by chromosomes and gene annotation. We provide strong evidence that a substantial proportion of variation in liability is explained by common SNPs, and thereby give insights into the genetic architecture of the diseases.
DATE PUBLISHED
2013 Feb 15
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2012/11/28
aheadofprint 2012/12/12
entrez 2012/11/30 06:00
pubmed 2012/11/30 06:00
medline 2013/07/06 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Lee SH Lee S Hong SH The University of Queensland, Queensland Brain Institute, Brisbane, QLD 4072, Australia.
Harold D Harold Denise D
Nyholt DR Nyholt Dale R DR
ANZGene Consortium
International Endogene Consortium
Genetic and Environmental Risk for Alzheimer's disease Consortium
Goddard ME Goddard Michael E ME
Zondervan KT Zondervan Krina T KT
Williams J Williams Julie J
Montgomery GW Montgomery Grant W GW
Wray NR Wray Naomi R NR
Visscher PM Visscher Peter M PM
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Harold Denise D
Sims Rebecca R
Gerrish Amy A
Chapman Jade J
Moskvina Valentina V
Abraham Richard R
Hollingworth Paul P
Hamshere Marian M
Pahwa Jaspreet Singh JS
Dowzell Kimberley K
Williams Amy A
Jones Nicola N
Thomas Charlene C
Stretton Alexandra A
Morgan Angharad A
Lovestone Simon S
Powell John J
Proitsi Petroula P
Lupton Michelle K MK
Brayne Carol C
Rubinsztein David C DC
Gill Michael M
Lawlor Brian B
Lynch Aoibhinn A
Morgan Kevin K
Brown Kristelle K
Passmore Peter P
Craig David D
McGuinness Bernadette B
Todd Stephen S
Holmes Clive C
Mann David D
Smith A David AD
Love Seth S
Kehoe Patrick G PG
Hardy John J
Mead Simon S
Fox Nick N
Rossor Martin M
Collinge John J
Maier Wolfgang W
Jessen Frank F
Heun Reiner R
Kölsch Heike H
Schürmann Britta B
van den Bussche Hendrik H
Heuser Isabella I
Kornhuber Johannes J
Wiltfang Jens J
Dichgans Martin M
Frölich Lutz L
Hampel Harald H
Hüll Michael M
Rujescu Dan D
Goate Alison A
Kauwe John S K JS
Cruchaga Carlos C
Nowotny Petra P
Morris John C JC
Mayo Kevin K
Livingston Gill G
Bass Nicholas J NJ
Gurling Hugh H
McQuillin Andrew A
Gwilliam Rhian R
Deloukas Panagiotis P
Nöthen Markus M MM
Holmans Peter P
O'Donovan Michael M
Owen Michael J MJ
Williams Julie J
Scott Rodney J RJ
Lechner-Scott Jeannette J
Moscato Pablo P
Booth David R DR
Stewart Graeme J GJ
Heard Robert N RN
Mason Deborah D
Griffiths Lyn L
Broadley Simon S
Brown Matthew A MA
Slee Mark M
Foote Simon J SJ
Stankovich Jim J
Taylor Bruce V BV
Wiley James J
Bahlo Melanie M
Perreau Victoria V
Field Judith J
Butzkueven Helmut H
Kilpatrick Trevor J TJ
Rubio Justin J
Marriott Mark M
Carroll William M WM
Kermode Allan G AG
Anderson Carl A CA
Gordon Scott D SD
Guo Qun Q
Henders Anjali K AK
Lambert Ann A
Lee Sang Hong SH
Kraft Peter P
Kennedy Stephen H SH
Macgregor Stuart S
Martin Nicholas G NG
Missmer Stacey A SA
Montgomery Grant W GW
Morris Andrew P AP
Nyholt Dale R DR
Painter Jodie N JN
Roseman Fenella F
Treloar Susan A SA
Visscher Peter M PM
Wallace Leanne L
Zondervan Krina T KT
JOURNAL
VOLUME: 22
ISSUE: 4
TITLE: Human molecular genetics
ISOABBREVIATION: Hum. Mol. Genet.
YEAR: 2013
MONTH: Feb
DAY: 15
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1460-2083
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Hum Mol Genet
COUNTRY: England
ISSNLINKING: 0964-6906
NLMUNIQUEID: 9208958
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
084766 Wellcome Trust United Kingdom
085235 Wellcome Trust United Kingdom
090532 Wellcome Trust United Kingdom
095317 Wellcome Trust United Kingdom
G0902227 Medical Research Council United Kingdom
MC_U123192748 Medical Research Council United Kingdom
MR/K013041/1 Medical Research Council United Kingdom
WT085235/Z/08/Z Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Alzheimer Disease genetics
Case-Control Studies genetics
Chromosomes, Human genetics
Endometriosis genetics
Female genetics
Gene Frequency genetics
Genetic Variation genetics
Genotype genetics
Humans genetics
Male genetics
Models, Genetic genetics
Molecular Sequence Annotation genetics
Multifactorial Inheritance genetics
Multiple Sclerosis genetics
Polymorphism, Single Nucleotide genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC3554206 NLM
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