A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol.
Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain and#8764;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 var...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Public Library of Science
2011
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| _version_ | 1826290541302644736 |
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| author | Surakka, I Isaacs, A Karssen, L Laurila, P Middelberg, R Tikkanen, E Ried, J Lamina, C Mangino, M Igl, W Hottenga, J Lagou, V van der Harst, P Mateo Leach, I Esko, T Kutalik, Z Wainwright, N Struchalin, M Sarin, A Kangas, A Viikari, J Perola, M Rantanen, T Petersen, A Soininen, P Johansson, A Soranzo, N Heath, A Papamarkou, T Prokopenko, I Tönjes, A Kronenberg, F Döring, A Rivadeneira, F Montgomery, G Whitfield, J Kähönen, M Lehtimäki, T Freimer, N Willemsen, G de Geus, E Palotie, A Sandhu, MS Waterworth, D Metspalu, A Stumvoll, M Uitterlinden, A Jula, A Navis, G Wijmenga, C Wolffenbuttel, B Taskinen, MR Ala-Korpela, M Kaprio, J Kyvik, K Boomsma, D Pedersen, N Gyllensten, U Wilson, J Rudan, I Campbell, H Pramstaller, P Spector, T Witteman, J Eriksson, J Salomaa, V Oostra, B Raitakari, O Wichmann, H Gieger, C Järvelin, MR Martin, N Hofman, A McCarthy, M Peltonen, L van Duijn, C Aulchenko, Y Ripatti, S |
| author_facet | Surakka, I Isaacs, A Karssen, L Laurila, P Middelberg, R Tikkanen, E Ried, J Lamina, C Mangino, M Igl, W Hottenga, J Lagou, V van der Harst, P Mateo Leach, I Esko, T Kutalik, Z Wainwright, N Struchalin, M Sarin, A Kangas, A Viikari, J Perola, M Rantanen, T Petersen, A Soininen, P Johansson, A Soranzo, N Heath, A Papamarkou, T Prokopenko, I Tönjes, A Kronenberg, F Döring, A Rivadeneira, F Montgomery, G Whitfield, J Kähönen, M Lehtimäki, T Freimer, N Willemsen, G de Geus, E Palotie, A Sandhu, MS Waterworth, D Metspalu, A Stumvoll, M Uitterlinden, A Jula, A Navis, G Wijmenga, C Wolffenbuttel, B Taskinen, MR Ala-Korpela, M Kaprio, J Kyvik, K Boomsma, D Pedersen, N Gyllensten, U Wilson, J Rudan, I Campbell, H Pramstaller, P Spector, T Witteman, J Eriksson, J Salomaa, V Oostra, B Raitakari, O Wichmann, H Gieger, C Järvelin, MR Martin, N Hofman, A McCarthy, M Peltonen, L van Duijn, C Aulchenko, Y Ripatti, S |
| author_sort | Surakka, I |
| collection | OXFORD |
| description | Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain and#8764;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 4.79x10<sup>-9</sup>. 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. |
| first_indexed | 2024-03-07T02:45:46Z |
| format | Journal article |
| id | oxford-uuid:ac030d24-25ec-47e3-a3d7-cd5f12a80660 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:45:46Z |
| publishDate | 2011 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:ac030d24-25ec-47e3-a3d7-cd5f12a806602022-03-27T03:26:03ZA genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ac030d24-25ec-47e3-a3d7-cd5f12a80660EnglishSymplectic Elements at OxfordPublic Library of Science2011Surakka, IIsaacs, AKarssen, LLaurila, PMiddelberg, RTikkanen, ERied, JLamina, CMangino, MIgl, WHottenga, JLagou, Vvan der Harst, PMateo Leach, IEsko, TKutalik, ZWainwright, NStruchalin, MSarin, AKangas, AViikari, JPerola, MRantanen, TPetersen, ASoininen, PJohansson, ASoranzo, NHeath, APapamarkou, TProkopenko, ITönjes, AKronenberg, FDöring, ARivadeneira, FMontgomery, GWhitfield, JKähönen, MLehtimäki, TFreimer, NWillemsen, Gde Geus, EPalotie, ASandhu, MSWaterworth, DMetspalu, AStumvoll, MUitterlinden, AJula, ANavis, GWijmenga, CWolffenbuttel, BTaskinen, MRAla-Korpela, MKaprio, JKyvik, KBoomsma, DPedersen, NGyllensten, UWilson, JRudan, ICampbell, HPramstaller, PSpector, TWitteman, JEriksson, JSalomaa, VOostra, BRaitakari, OWichmann, HGieger, CJärvelin, MRMartin, NHofman, AMcCarthy, MPeltonen, Lvan Duijn, CAulchenko, YRipatti, SRecent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain and#8764;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 4.79x10<sup>-9</sup>. 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. |
| spellingShingle | Surakka, I Isaacs, A Karssen, L Laurila, P Middelberg, R Tikkanen, E Ried, J Lamina, C Mangino, M Igl, W Hottenga, J Lagou, V van der Harst, P Mateo Leach, I Esko, T Kutalik, Z Wainwright, N Struchalin, M Sarin, A Kangas, A Viikari, J Perola, M Rantanen, T Petersen, A Soininen, P Johansson, A Soranzo, N Heath, A Papamarkou, T Prokopenko, I Tönjes, A Kronenberg, F Döring, A Rivadeneira, F Montgomery, G Whitfield, J Kähönen, M Lehtimäki, T Freimer, N Willemsen, G de Geus, E Palotie, A Sandhu, MS Waterworth, D Metspalu, A Stumvoll, M Uitterlinden, A Jula, A Navis, G Wijmenga, C Wolffenbuttel, B Taskinen, MR Ala-Korpela, M Kaprio, J Kyvik, K Boomsma, D Pedersen, N Gyllensten, U Wilson, J Rudan, I Campbell, H Pramstaller, P Spector, T Witteman, J Eriksson, J Salomaa, V Oostra, B Raitakari, O Wichmann, H Gieger, C Järvelin, MR Martin, N Hofman, A McCarthy, M Peltonen, L van Duijn, C Aulchenko, Y Ripatti, S A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol. |
| title | A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol. |
| title_full | A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol. |
| title_fullStr | A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol. |
| title_full_unstemmed | A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol. |
| title_short | A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol. |
| title_sort | 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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genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT waterworthd genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT metspalua genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT stumvollm genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT uitterlindena genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT julaa genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT navisg genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT wijmengac genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT wolffenbuttelb genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT taskinenmr genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT alakorpelam genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT kaprioj genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT kyvikk genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT boomsmad genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT pedersenn genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT gyllenstenu genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT wilsonj genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT rudani genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT campbellh genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT pramstallerp genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT spectort genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT wittemanj genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT erikssonj genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT salomaav genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT oostrab genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT raitakario genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT wichmannh genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT giegerc genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT jarvelinmr genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT martinn genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT hofmana genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT mccarthym genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT peltonenl genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT vanduijnc genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT aulchenkoy genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol AT ripattis genomewidescreenforinteractionsrevealsanewlocuson4p15modifyingtheeffectofwaisttohipratioontotalcholesterol |