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A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol

Surakka, Ida ; Isaacs, Aaron ; Karssen, Lennart C ; Laurila, Pirkka-Pekka P ; Middelberg, Rita P S ; Tikkanen, Emmi ; Ried, Janina S ; Lamina, Claudia ; Mangino, Massimo ; Igl, Wilmar ; Hottenga, Jouke-Jan ; Lagou, Vasiliki ; van der Harst, Pim ; Mateo Leach, Irene ; Esko, Tõnu ; Kutalik, Zoltán ; Wainwright, Nicholas W ; Struchalin, Maksim V ; Sarin, Antti-Pekka ; Kangas, Antti J ; Viikari, Jorma S ; Perola, Markus ; Rantanen, Taina ; Petersen, Ann-Kristin ; Soininen, Pasi ; Johansson, Asa ; Soranzo, Nicole ; Heath, Andrew C ; Papamarkou, Theodore ; Prokopenko, Inga ; Tönjes, Anke ; Kronenberg, Florian ; Döring, Angela ; Rivadeneira, Fernando ; Montgomery, Grant W ; Whitfield, John B ; Kähönen, Mika ; Lehtimäki, Terho ; Freimer, Nelson B ; Willemsen, Gonneke ; de Geus, Eco J C ; Palotie, Aarno ; Sandhu, Manj S ; Waterworth, Dawn M ; Metspalu, Andres ; Stumvoll, Michael ; Uitterlinden, André G ; Jula, Antti ; Navis, Gerjan ; Wijmenga, Cisca ; Wolffenbuttel, Bruce H R ; Taskinen, Marja-Riitta ; Ala-Korpela, Mika ; Kaprio, Jaakko ; Kyvik, Kirsten O ; Boomsma, Dorret I ; Pedersen, Nancy L ; Gyllensten, Ulf ; Wilson, James F ; Rudan, Igor ; Campbell, Harry ; Pramstaller, Peter P ; Spector, Tim D ; Witteman, Jacqueline C M ; Eriksson, Johan G ; Salomaa, Veikko ; Oostra, Ben A ; Raitakari, Olli T ; Wichmann, H-Erich ; Gieger, Christian ; Järvelin, Marjo-Riitta ; Martin, Nicholas G ; Hofman, Albert ; McCarthy, Mark I ; Peltonen, Leena ; van Duijn, Cornelia M ; Aulchenko, Yurii S ; Ripatti, Samuli Gibson, Greg

PLoS genetics, 2011-10, Vol.7 (10), p.e1002333-e1002333 [Periódico revisado por pares]

United States: Public Library of Science

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A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol
Autor: Surakka, Ida ; Isaacs, Aaron ; Karssen, Lennart C ; Laurila, Pirkka-Pekka P ; Middelberg, Rita P S ; Tikkanen, Emmi ; Ried, Janina S ; Lamina, Claudia ; Mangino, Massimo ; Igl, Wilmar ; Hottenga, Jouke-Jan ; Lagou, Vasiliki ; van der Harst, Pim ; Mateo Leach, Irene ; Esko, Tõnu ; Kutalik, Zoltán ; Wainwright, Nicholas W ; Struchalin, Maksim V ; Sarin, Antti-Pekka ; Kangas, Antti J ; Viikari, Jorma S ; Perola, Markus ; Rantanen, Taina ; Petersen, Ann-Kristin ; Soininen, Pasi ; Johansson, Asa ; Soranzo, Nicole ; Heath, Andrew C ; Papamarkou, Theodore ; Prokopenko, Inga ; Tönjes, Anke ; Kronenberg, Florian ; Döring, Angela ; Rivadeneira, Fernando ; Montgomery, Grant W ; Whitfield, John B ; Kähönen, Mika ; Lehtimäki, Terho ; Freimer, Nelson B ; Willemsen, Gonneke ; de Geus, Eco J C ; Palotie, Aarno ; Sandhu, Manj S ; Waterworth, Dawn M ; Metspalu, Andres ; Stumvoll, Michael ; Uitterlinden, André G ; Jula, Antti ; Navis, Gerjan ; Wijmenga, Cisca ; Wolffenbuttel, Bruce H R ; Taskinen, Marja-Riitta ; Ala-Korpela, Mika ; Kaprio, Jaakko ; Kyvik, Kirsten O ; Boomsma, Dorret I ; Pedersen, Nancy L ; Gyllensten, Ulf ; Wilson, James F ; Rudan, Igor ; Campbell, Harry ; Pramstaller, Peter P ; Spector, Tim D ; Witteman, Jacqueline C M ; Eriksson, Johan G ; Salomaa, Veikko ; Oostra, Ben A ; Raitakari, Olli T ; Wichmann, H-Erich ; Gieger, Christian ; Järvelin, Marjo-Riitta ; Martin, Nicholas G ; Hofman, Albert ; McCarthy, Mark I ; Peltonen, Leena ; van Duijn, Cornelia M ; Aulchenko, Yurii S ; Ripatti, Samuli
Gibson, Greg
Assuntos: Adipose Tissue - metabolism ; Biology ; Body Fat Distribution ; Cadherins - genetics ; Cholesterol ; Cholesterol - blood ; Cholesterol - genetics ; Chromosome Mapping ; Chromosomes, Human, Pair 4 - genetics ; Cigarettes ; Confidence intervals ; Councils ; Epidemiology ; Gene expression ; Genome-Wide Association Study ; Genomes ; Genomics ; Genotype ; Grants ; Health sciences ; Humans ; Lipids ; Lipids - blood ; Lipids - genetics ; Lipoproteins ; Lipoproteins - blood ; Lipoproteins - genetics ; Medicin och hälsovetenskap ; Phenotype ; Physiological aspects ; Polymorphism, Single Nucleotide ; Population ; Principal components analysis ; Protocadherins ; Quantitative Trait Loci - genetics ; Risk Factors ; Single nucleotide polymorphisms ; Triglycerides ; Triglycerides - blood ; Triglycerides - genetics ; Waist-Hip Ratio ; White People - genetics
É parte de: PLoS genetics, 2011-10, Vol.7 (10), p.e1002333-e1002333
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Conceived and designed the experiments: LP CMD YSA SR. Performed the experiments: IS AI LCK. Analyzed the data: IS AI LCK PPL RPSM ET JSR CL MM WI JJH VL PH IML TE ZK NWW MVS APS AJK. Contributed reagents/materials/analysis tools: JSV MP TR AKP PS ÅJ NS ACH TP IP AT FK AD FR GWM JBW MK TL NBF GW EJCG AP MSS DW AM MS AGU AJ GN CW BHRW MRT MAK JK KOK DIB NLP UG JFW IR HC PPP TDS JCMW JGE VS BAO OTR HEW CG MRJ NGM AH. Wrote the paper: IS AI MIM CMD YSA SR.
Deceased.
These authors also contributed equally to this work.
Descrição: Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain ∼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 4.79×10(-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.
Editor: United States: Public Library of Science
Idioma: Inglês

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A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol

United States: Public Library of Science

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