A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol

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Fältnamn	Indikatorer	Metadata
000		06037naa a2201237 4500
001		oai:DiVA.org:uu-162708
003		SwePub
008		111205s2011 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
009		oai:prod.swepub.kib.ki.se:123571451
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1627082 URI
024	7	a https://doi.org/10.1371/journal.pgen.10023332 DOI
024	7	a http://kipublications.ki.se/Default.aspx?queryparsed=id:1235714512 URI
040		a (SwePub)uud (SwePub)ki
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Surakka, Ida4 aut
245	1 0	a A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol
264		c 2011-10-20
264	1	b Public Library of Science (PLoS),c 2011
338		a print2 rdacarrier
520		a Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain similar to 25% of the heritability of the phenotypes. To date, no unbiased screen for gene-environment interactions for circulating lipids has been reported. We screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA) data from 18 population-based cohorts with European ancestry (maximum N = 32,225). We collected 8 further cohorts (N = 17,102) for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR) on total cholesterol (TC) with a combined P-value of 4.79 x 10(-9). There were two potential candidate genes in the region, PCDH7 and CCKAR, with differential expression levels for rs6448771 genotypes in adipose tissue. The effect of WHR on TC was strongest for individuals carrying two copies of G allele, for whom a one standard deviation (sd) difference in WHR corresponds to 0.19 sd difference in TC concentration, while for A allele homozygous the difference was 0.12 sd. Our findings may open up possibilities for targeted intervention strategies for people characterized by specific genomic profiles. However, more refined measures of both body-fat distribution and metabolic measures are needed to understand how their joint dynamics are modified by the newly found locus.
700	1	a Isaacs, Aaron4 aut
700	1	a Karssen, Lennart C.4 aut
700	1	a Laurila, Pirkka-Pekka P.4 aut
700	1	a Middelberg, Rita P. S.4 aut
700	1	a Tikkanen, Emmi4 aut
700	1	a Ried, Janina S.4 aut
700	1	a Lamina, Claudia4 aut
700	1	a Mangino, Massimo4 aut
700	1	a Igl, Wilmar4 aut
700	1	a Hottenga, Jouke-Jan4 aut
700	1	a Lagou, Vasiliki4 aut
700	1	a van der Harst, Pim4 aut
700	1	a Leach, Irene Mateo4 aut
700	1	a Esko, Tonu4 aut
700	1	a Kutalik, Zoltan4 aut
700	1	a Wainwright, Nicholas W.4 aut
700	1	a Struchalin, Maksim V.4 aut
700	1	a Sarin, Antti-Pekka4 aut
700	1	a Kangas, Antti J.4 aut
700	1	a Viikari, Jorma S.4 aut
700	1	a Perola, Markus4 aut
700	1	a Rantanen, Taina4 aut
700	1	a Petersen, Ann-Kristin4 aut
700	1	a Soininen, Pasi4 aut
700	1	a Johansson, Åsau Uppsala universitet,Genomik,Gyllensten4 aut0 (Swepub:uu)asjoh108
700	1	a Soranzo, Nicole4 aut
700	1	a Heath, Andrew C.4 aut
700	1	a Papamarkou, Theodore4 aut
700	1	a Prokopenko, Inga4 aut
700	1	a Toenjes, Anke4 aut
700	1	a Kronenberg, Florian4 aut
700	1	a Doering, Angela4 aut
700	1	a Rivadeneira, Fernando4 aut
700	1	a Montgomery, Grant W.4 aut
700	1	a Whitfield, John B.4 aut
700	1	a Kahonen, Mika4 aut
700	1	a Lehtimaki, Terho4 aut
700	1	a Freimer, Nelson B.4 aut
700	1	a Willemsen, Gonneke4 aut
700	1	a de Geus, Eco J. C.4 aut
700	1	a Palotie, Aarno4 aut
700	1	a Sandhu, Manj S.4 aut
700	1	a Waterworth, Dawn M.4 aut
700	1	a Metspalu, Andres4 aut
700	1	a Stumvoll, Michael4 aut
700	1	a Uitterlinden, Andre G.4 aut
700	1	a Jula, Antti4 aut
700	1	a Navis, Gerjan4 aut
700	1	a Wijmenga, Cisca4 aut
700	1	a Wolffenbuttel, Bruce H. R.4 aut
700	1	a Taskinen, Marja-Riitta4 aut
700	1	a Ala-Korpela, Mika4 aut
700	1	a Kaprio, Jaakko4 aut
700	1	a Kyvik, Kirsten O.4 aut
700	1	a Boomsma, Dorret I.4 aut
700	1	a Pedersen, Nancy L.u Karolinska Institutet4 aut
700	1	a Gyllensten, Ulfu Uppsala universitet,Genomik,Gyllensten4 aut0 (Swepub:uu)ulfgyll
700	1	a Wilson, James F.4 aut
700	1	a Rudan, Igor4 aut
700	1	a Campbell, Harry4 aut
700	1	a Pramstaller, Peter P.4 aut
700	1	a Spector, Tim D.4 aut
700	1	a Witteman, Jacqueline C. M.4 aut
700	1	a Eriksson, Johan G.4 aut
700	1	a Salomaa, Veikko4 aut
700	1	a Oostra, Ben A.4 aut
700	1	a Raitakari, Olli T.4 aut
700	1	a Wichmann, H. -Erich4 aut
700	1	a Gieger, Christian4 aut
700	1	a Jaervelin, Marjo-Riitta4 aut
700	1	a Martin, Nicholas G.4 aut
700	1	a Hofman, Albert4 aut
700	1	a McCarthy, Mark I.4 aut
700	1	a Peltonen, Leena4 aut
700	1	a van Duijn, Cornelia M.4 aut
700	1	a Aulchenko, Yurii S.4 aut
700	1	a Ripatti, Samuli4 aut
710	2	a Uppsala universitetb Genomik4 org
773	0	t PLoS Geneticsd : Public Library of Science (PLoS)g 7:10, s. e1002333-q 7:10<e1002333-x 1553-7390x 1553-7404
856	4	u https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002333&type=printable
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-162708
856	4 8	u https://doi.org/10.1371/journal.pgen.1002333
856	4 8	u http://kipublications.ki.se/Default.aspx?queryparsed=id:123571451

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Av författaren/redakt...: Surakka, Ida; Isaacs, Aaron; Karssen, Lennart ...; Laurila, Pirkka- ...; Middelberg, Rita ...; Tikkanen, Emmi; visa fler...; Ried, Janina S.; Lamina, Claudia; Mangino, Massimo; Igl, Wilmar; Hottenga, Jouke- ...; Lagou, Vasiliki; van der Harst, P ...; Leach, Irene Mat ...; Esko, Tonu; Kutalik, Zoltan; Wainwright, Nich ...; Struchalin, Maks ...; Sarin, Antti-Pek ...; Kangas, Antti J.; Viikari, Jorma S ...; Perola, Markus; Rantanen, Taina; Petersen, Ann-Kr ...; Soininen, Pasi; Johansson, Åsa; Soranzo, Nicole; Heath, Andrew C.; Papamarkou, Theo ...; Prokopenko, Inga; Toenjes, Anke; Kronenberg, Flor ...; Doering, Angela; Rivadeneira, Fer ...; Montgomery, Gran ...; Whitfield, John ...; Kahonen, Mika; Lehtimaki, Terho; Freimer, Nelson ...; Willemsen, Gonne ...; de Geus, Eco J. ...; Palotie, Aarno; Sandhu, Manj S.; Waterworth, Dawn ...; Metspalu, Andres; Stumvoll, Michae ...; Uitterlinden, An ...; Jula, Antti; Navis, Gerjan; Wijmenga, Cisca; Wolffenbuttel, B ...; Taskinen, Marja- ...; Ala-Korpela, Mik ...; Kaprio, Jaakko; Kyvik, Kirsten O ...; Boomsma, Dorret ...; Pedersen, Nancy ...; Gyllensten, Ulf; Wilson, James F.; Rudan, Igor; Campbell, Harry; Pramstaller, Pet ...; Spector, Tim D.; Witteman, Jacque ...; Eriksson, Johan ...; Salomaa, Veikko; Oostra, Ben A.; Raitakari, Olli ...; Wichmann, H. -Er ...; Gieger, Christia ...; Jaervelin, Marjo ...; Martin, Nicholas ...; Hofman, Albert; McCarthy, Mark I ...; Peltonen, Leena; van Duijn, Corne ...; Aulchenko, Yurii ...; Ripatti, Samuli; visa färre...

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