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
22829771
TITLE
Evidence of inbreeding depression on human height.
ABSTRACT
Stature is a classical and highly heritable complex trait, with 80%-90% of variation explained by genetic factors. In recent years, genome-wide association studies (GWAS) have successfully identified many common additive variants influencing human height; however, little attention has been given to the potential role of recessive genetic effects. Here, we investigated genome-wide recessive effects by an analysis of inbreeding depression on adult height in over 35,000 people from 21 different population samples. We found a highly significant inverse association between height and genome-wide homozygosity, equivalent to a height reduction of up to 3 cm in the offspring of first cousins compared with the offspring of unrelated individuals, an effect which remained after controlling for the effects of socio-economic status, an important confounder (χ(2) = 83.89, df = 1; p = 5.2 × 10(-20)). There was, however, a high degree of heterogeneity among populations: whereas the direction of the effect was consistent across most population samples, the effect size differed significantly among populations. It is likely that this reflects true biological heterogeneity: whether or not an effect can be observed will depend on both the variance in homozygosity in the population and the chance inheritance of individual recessive genotypes. These results predict that multiple, rare, recessive variants influence human height. Although this exploratory work focuses on height alone, the methodology developed is generally applicable to heritable quantitative traits (QT), paving the way for an investigation into inbreeding effects, and therefore genetic architecture, on a range of QT of biomedical importance.
DATE PUBLISHED
2012
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2012/01/19
accepted 2012/03/02
epublish 2012/07/19
entrez 2012/07/26 06:00
pubmed 2012/07/26 06:00
medline 2013/01/05 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
McQuillan R McQuillan Ruth R Centre for Population Health Sciences, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
Eklund N Eklund Niina N
Pirastu N Pirastu Nicola N
Kuningas M Kuningas Maris M
McEvoy BP McEvoy Brian P BP
Esko T Esko Tõnu T
Corre T Corre Tanguy T
Davies G Davies Gail G
Kaakinen M Kaakinen Marika M
Lyytikäinen LP Lyytikäinen Leo-Pekka LP
Kristiansson K Kristiansson Kati K
Havulinna AS Havulinna Aki S AS
Gögele M Gögele Martin M
Vitart V Vitart Veronique V
Tenesa A Tenesa Albert A
Aulchenko Y Aulchenko Yurii Y
Hayward C Hayward Caroline C
Johansson A Johansson Asa A
Boban M Boban Mladen M
Ulivi S Ulivi Sheila S
Robino A Robino Antonietta A
Boraska V Boraska Vesna V
Igl W Igl Wilmar W
Wild SH Wild Sarah H SH
Zgaga L Zgaga Lina L
Amin N Amin Najaf N
Theodoratou E Theodoratou Evropi E
Polašek O Polašek Ozren O
Girotto G Girotto Giorgia G
Lopez LM Lopez Lorna M LM
Sala C Sala Cinzia C
Lahti J Lahti Jari J
Laatikainen T Laatikainen Tiina T
Prokopenko I Prokopenko Inga I
Kals M Kals Mart M
Viikari J Viikari Jorma J
Yang J Yang Jian J
Pouta A Pouta Anneli A
Estrada K Estrada Karol K
Hofman A Hofman Albert A
Freimer N Freimer Nelson N
Martin NG Martin Nicholas G NG
Kähönen M Kähönen Mika M
Milani L Milani Lili L
Heliövaara M Heliövaara Markku M
Vartiainen E Vartiainen Erkki E
Räikkönen K Räikkönen Katri K
Masciullo C Masciullo Corrado C
Starr JM Starr John M JM
Hicks AA Hicks Andrew A AA
Esposito L Esposito Laura L
Kolčić I Kolčić Ivana I
Farrington SM Farrington Susan M SM
Oostra B Oostra Ben B
Zemunik T Zemunik Tatijana T
Campbell H Campbell Harry H
Kirin M Kirin Mirna M
Pehlic M Pehlic Marina M
Faletra F Faletra Flavio F
Porteous D Porteous David D
Pistis G Pistis Giorgio G
Widén E Widén Elisabeth E
Salomaa V Salomaa Veikko V
Koskinen S Koskinen Seppo S
Fischer K Fischer Krista K
Lehtimäki T Lehtimäki Terho T
Heath A Heath Andrew A
McCarthy MI McCarthy Mark I MI
Rivadeneira F Rivadeneira Fernando F
Montgomery GW Montgomery Grant W GW
Tiemeier H Tiemeier Henning H
Hartikainen AL Hartikainen Anna-Liisa AL
Madden PA Madden Pamela A F PA
d'Adamo P d'Adamo Pio P
Hastie ND Hastie Nicholas D ND
Gyllensten U Gyllensten Ulf U
Wright AF Wright Alan F AF
van Duijn CM van Duijn Cornelia M CM
Dunlop M Dunlop Malcolm M
Rudan I Rudan Igor I
Gasparini P Gasparini Paolo P
Pramstaller PP Pramstaller Peter P PP
Deary IJ Deary Ian J IJ
Toniolo D Toniolo Daniela D
Eriksson JG Eriksson Johan G JG
Jula A Jula Antti A
Raitakari OT Raitakari Olli T OT
Metspalu A Metspalu Andres A
Perola M Perola Markus M
Järvelin MR Järvelin Marjo-Riitta MR
Uitterlinden A Uitterlinden André A
Visscher PM Visscher Peter M PM
Wilson JF Wilson James F JF
ROHgen Consortium
INVESTIGATORS
JOURNAL
VOLUME: 8
ISSUE: 7
TITLE: PLoS genetics
ISOABBREVIATION: PLoS Genet.
YEAR: 2012
MONTH:
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
Meta-Analysis
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
090532 Wellcome Trust United Kingdom
12076 Cancer Research UK United Kingdom
BB/F019394/1 Biotechnology and Biological Sciences Research Council United Kingdom
CZB/4/505 Chief Scientist Office United Kingdom
CZB/4/710 Chief Scientist Office United Kingdom
ETM/55 Chief Scientist Office United Kingdom
G0700704 Medical Research Council United Kingdom
G0701120 Medical Research Council United Kingdom
K05 AA017688 NIAAA NIH HHS United States
MC_PC_U127561128 Medical Research Council United Kingdom
MC_U127527198 Medical Research Council United Kingdom
MC_U127561128 Medical Research Council United Kingdom
Biotechnology and Biological Sciences Research Council United Kingdom
Cancer Research UK United Kingdom
Chief Scientist Office United Kingdom
Medical Research Council United Kingdom
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Aged
Body Height genetics
Consanguinity genetics
Databases, Genetic genetics
Family genetics
Female genetics
Genes, Recessive genetics
Genetic Heterogeneity genetics
Genome-Wide Association Study genetics
Homozygote genetics
Humans genetics
Male genetics
Middle Aged genetics
Polymorphism, Single Nucleotide genetics
Quantitative Trait, Heritable genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC3400549 NLM
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