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Common variants nea...
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Loos, Ruth J. F.
(author)
Common variants near MC4R are associated with fat mass, weight and risk of obesity
- Article/chapterEnglish2008
Publisher, publication year, extent ...
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2008-05-04
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Springer Science and Business Media LLC,2008
Numbers
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LIBRIS-ID:oai:lup.lub.lu.se:e5825bc5-a319-4b99-9dc2-d028af4cf8e1
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https://lup.lub.lu.se/record/1201605URI
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https://doi.org/10.1038/ng.140DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Lindgren, Cecilia M.
(author)
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Li, Shengxu
(author)
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Wheeler, Eleanor
(author)
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Zhao, Jing Hua
(author)
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Prokopenko, Inga
(author)
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Inouye, Michael
(author)
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Freathy, Rachel M.
(author)
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Attwood, Antony P.
(author)
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Beckmann, Jacques S.
(author)
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Berndt, Sonja I.
(author)
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Bergmann, Sven
(author)
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Bennett, Amanda J.
(author)
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Bingham, Sheila A.
(author)
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Bochud, Murielle
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Brown, Morris
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Cauchi, Stephane
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Connell, John M.
(author)
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Cooper, Cyrus
(author)
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Smith, George Davey
(author)
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Day, Ian
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Dina, Christian
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De, Subhajyoti
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Dermitzakis, Emmanouil T.
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Doney, Alex S. F.
(author)
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Elliott, Katherine S.
(author)
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Elliott, Paul
(author)
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Evans, David M.
(author)
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Farooqi, I. Sadaf
(author)
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Froguel, Philippe
(author)
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Ghori, Jilur
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Groves, Christopher J.
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Gwilliam, Rhian
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Hadley, David
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Hall, Alistair S.
(author)
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Hattersley, Andrew T.
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Hebebrand, Johannes
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Heid, Iris M.
(author)
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Herrera, Blanca
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Hinney, Anke
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Hunt, Sarah E.
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Jarvelin, Marjo-Riitta
(author)
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Johnson, Toby
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Jolley, Jennifer D. M.
(author)
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Karpe, Fredrik
(author)
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Keniry, Andrew
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Khaw, Kay-Tee
(author)
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Luben, Robert N.
(author)
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Ridderstråle, MartinLund University,Lunds universitet,Diabetes - klinisk obesitasforskning,Forskargrupper vid Lunds universitet,Diabetes - Clinical Obesity,Lund University Research Groups(Swepub:lu)endo-mri
(author)
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Groop, LeifLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)endo-lgr
(author)
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Diabetes - klinisk obesitasforskningForskargrupper vid Lunds universitet
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et al.
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In:Nature Genetics: Springer Science and Business Media LLC40:6, s. 768-7751546-17181061-4036
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Loos, Ruth J. F.
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Lindgren, Cecili ...
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Li, Shengxu
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Wheeler, Eleanor
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Zhao, Jing Hua
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Prokopenko, Inga
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Inouye, Michael
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Freathy, Rachel ...
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Attwood, Antony ...
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Beckmann, Jacque ...
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Berndt, Sonja I.
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Bergmann, Sven
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Bennett, Amanda ...
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Bingham, Sheila ...
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Bochud, Murielle
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Brown, Morris
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Cauchi, Stephane
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Connell, John M.
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Cooper, Cyrus
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Smith, George Da ...
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Day, Ian
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Dina, Christian
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De, Subhajyoti
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Dermitzakis, Emm ...
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Doney, Alex S. F ...
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Elliott, Katheri ...
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Elliott, Paul
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Evans, David M.
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Farooqi, I. Sada ...
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Froguel, Philipp ...
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Ghori, Jilur
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Groves, Christop ...
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Gwilliam, Rhian
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Hadley, David
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Hall, Alistair S ...
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Hattersley, Andr ...
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Hebebrand, Johan ...
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Heid, Iris M.
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Herrera, Blanca
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Hinney, Anke
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Hunt, Sarah E.
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Jarvelin, Marjo- ...
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Johnson, Toby
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Jolley, Jennifer ...
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Karpe, Fredrik
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Keniry, Andrew
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Khaw, Kay-Tee
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Luben, Robert N.
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Ridderstråle, Ma ...
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Groop, Leif
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- MEDICAL AND HEALTH SCIENCES
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Nature Genetics
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Lund University