Genetic Epidemiology, Psychiatric Genetics, Asthma 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.
QIMR Home Page
GenEpi Home Page
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
16565746
TITLE
Assumption-free estimation of heritability from genome-wide identity-by-descent sharing between full siblings.
ABSTRACT
The study of continuously varying, quantitative traits is important in evolutionary biology, agriculture, and medicine. Variation in such traits is attributable to many, possibly interacting, genes whose expression may be sensitive to the environment, which makes their dissection into underlying causative factors difficult. An important population parameter for quantitative traits is heritability, the proportion of total variance that is due to genetic factors. Response to artificial and natural selection and the degree of resemblance between relatives are all a function of this parameter. Following the classic paper by R. A. Fisher in 1918, the estimation of additive and dominance genetic variance and heritability in populations is based upon the expected proportion of genes shared between different types of relatives, and explicit, often controversial and untestable models of genetic and non-genetic causes of family resemblance. With genome-wide coverage of genetic markers it is now possible to estimate such parameters solely within families using the actual degree of identity-by-descent sharing between relatives. Using genome scans on 4,401 quasi-independent sib pairs of which 3,375 pairs had phenotypes, we estimated the heritability of height from empirical genome-wide identity-by-descent sharing, which varied from 0.374 to 0.617 (mean 0.498, standard deviation 0.036). The variance in identity-by-descent sharing per chromosome and per genome was consistent with theory. The maximum likelihood estimate of the heritability for height was 0.80 with no evidence for non-genetic causes of sib resemblance, consistent with results from independent twin and family studies but using an entirely separate source of information. Our application shows that it is feasible to estimate genetic variance solely from within-family segregation and provides an independent validation of previously untestable assumptions. Given sufficient data, our new paradigm will allow the estimation of genetic variation for disease susceptibility and quantitative traits that is free from confounding with non-genetic factors and will allow partitioning of genetic variation into additive and non-additive components.
DATE PUBLISHED
2006 Mar
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2005/12/07
accepted 2006/02/06
aheadofprint 2006/03/24
pubmed 2006/03/28 09:00
medline 2006/08/01 09:00
entrez 2006/03/28 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Visscher PM Visscher Peter M PM Genetic Epidemiology Group, Queensland Institute of Medical Research, Brisbane, Australia. peter.visscher@qimr.edu.au
Medland SE Medland Sarah E SE
Ferreira MA Ferreira Manuel A R MA
Morley KI Morley Katherine I KI
Zhu G Zhu Gu G
Cornes BK Cornes Belinda K BK
Montgomery GW Montgomery Grant W GW
Martin NG Martin Nicholas G NG
INVESTIGATORS
JOURNAL
VOLUME: 2
ISSUE: 3
TITLE: PLoS genetics
ISOABBREVIATION: PLoS Genet.
YEAR: 2006
MONTH: Mar
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1553-7404
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: PLoS Genet
COUNTRY: United States
ISSNLINKING: 1553-7390
NLMUNIQUEID: 101239074
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Behav Genet. 1993 Jan;23(1):21-7 8476388
Cites Am J Hum Genet. 1990 Dec;47(6):957-67 2239972
Cites Am J Hum Genet. 1995 Jun;56(6):1468-76 7762570
Cites Science. 1995 Jun 16;268(5217):1584-9 7777857
Cites Biometrics. 1994 Dec;50(4):1171-7 7786999
Cites Behav Genet. 1995 Jul;25(4):327-35 7575361
Cites Am J Hum Genet. 1996 Feb;58(2):408-19 8571968
Cites Am J Hum Genet. 1996 Apr;58(4):836-43 8644748
Cites Hum Hered. 1996 Mar-Apr;46(2):61-70 8666414
Cites Am J Hum Genet. 1999 Aug;65(2):483-92 10417291
Cites Genetics. 1999 Aug;152(4):1753-66 10430599
Cites Nature. 2005 Mar 17;434(7031):325-37 15772651
Cites Philos Trans R Soc Lond B Biol Sci. 2005 Jul 29;360(1459):1457-67 16048788
Cites Genet Epidemiol. 2005 Nov;29(3):215-24 16121355
Cites Twin Res Hum Genet. 2005 Dec;8(6):616-32 16363087
Cites Nature. 1997 Jul 31;388(6641):468-71 9242404
Cites Am J Hum Genet. 2000 May;66(5):1616-30 10762547
Cites Mol Ecol. 2000 Sep;9(9):1195-204 10972759
Cites Adv Genet. 2001;42:299-322 11037329
Cites Eur J Hum Genet. 2001 May;9(5):335-40 11378821
Cites Am J Hum Genet. 2001 Jun;68(6):1527-32 11353401
Cites Twin Res. 2001 Feb;4(1):19-24 11665320
Cites Twin Res. 2001 Feb;4(1):48-56 11665325
Cites Nat Genet. 2002 Jan;30(1):97-101 11731797
Cites Ann Hum Genet. 2001 Nov;65(Pt 6):583-601 11851988
Cites Bioinformatics. 2003 Jan;19(1):149-50 12499305
Cites Twin Res. 2003 Oct;6(5):354-60 14624719
Cites Twin Res. 2003 Oct;6(5):399-408 14624724
Cites Am J Hum Genet. 2004 Jan;74(1):62-72 14681832
Cites Twin Res. 2004 Apr;7(2):197-210 15169604
Cites Am J Hum Genet. 2004 Dec;75(6):1143-8 15486828
Cites Behav Genet. 1972 Mar;2(1):3-19 4157472
Cites Ann Hum Genet. 1976 May;39(4):485-91 952492
Cites Theor Popul Biol. 1977 Feb;11(1):60-80 404725
Cites Hum Hered. 1979;29(1):37-41 761921
Cites Ann Hum Genet. 1979 Oct;43(2):177-86 525976
Cites Am J Hum Genet. 1994 Jun;54(6):1104-9 8198133
GRANTS
GRANTID AGENCY COUNTRY
AA007535 NIAAA NIH HHS United States
AA013320 NIAAA NIH HHS United States
AA013326 NIAAA NIH HHS United States
AA014041 NIAAA NIH HHS United States
AA07728 NIAAA NIH HHS United States
AA10249 NIAAA NIH HHS United States
AA11998 NIAAA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Body Height
Chromosome Mapping
Family Health
Genetic Markers
Genetic Variation
Genome
Humans
Likelihood Functions
Models, Genetic
Models, Statistical
Phenotype
Siblings
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Genetic Markers
OTHER ID's
OTHERID SOURCE
PMC1413498 NLM