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1. Associations between exploratory dietary patterns and incident type 2 diabetes: a federated meta-analysis of individual participant data from 25 cohort studies.

Author

Jannasch, F, Dietrich, S, Bishop, TRP, Pearce, M, Fanidi, A, O'Donoghue, G, O'Gorman, D, Marques-Vidal, P, Vollenweider, P, Bes-Rastrollo, M, Byberg, L, Wolk, A, Hashemian, M, Malekzadeh, R, Poustchi, H, Luft, VC, de Matos, SMA, Kim, J, Kim, MK, Kim, Y, Stern, D, Lajous, M, Magliano, DJ, Shaw, JE, Akbaraly, T, Kivimaki, M, Maskarinec, G, Le Marchand, L, Martínez-González, MÁ, Soedamah-Muthu, SS, EPIC-InterAct Consortium, Wareham, NJ, Forouhi, NG, Schulze, MB, Jannasch, F, Dietrich, S, Bishop, TRP, Pearce, M, Fanidi, A, O'Donoghue, G, O'Gorman, D, Marques-Vidal, P, Vollenweider, P, Bes-Rastrollo, M, Byberg, L, Wolk, A, Hashemian, M, Malekzadeh, R, Poustchi, H, Luft, VC, de Matos, SMA, Kim, J, Kim, MK, Kim, Y, Stern, D, Lajous, M, Magliano, DJ, Shaw, JE, Akbaraly, T, Kivimaki, M, Maskarinec, G, Le Marchand, L, Martínez-González, MÁ, Soedamah-Muthu, SS, EPIC-InterAct Consortium, Wareham, NJ, Forouhi, NG, and Schulze, MB

Abstract

PURPOSE: In several studies, exploratory dietary patterns (DP), derived by principal component analysis, were inversely or positively associated with incident type 2 diabetes (T2D). However, findings remained study-specific, inconsistent and rarely replicated. This study aimed to investigate the associations between DPs and T2D in multiple cohorts across the world. METHODS: This federated meta-analysis of individual participant data was based on 25 prospective cohort studies from 5 continents including a total of 390,664 participants with a follow-up for T2D (3.8-25.0 years). After data harmonization across cohorts we evaluated 15 previously identified T2D-related DPs for association with incident T2D estimating pooled incidence rate ratios (IRR) and confidence intervals (CI) by Piecewise Poisson regression and random-effects meta-analysis. RESULTS: 29,386 participants developed T2D during follow-up. Five DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, were associated with higher incidence of T2D. The strongest association was observed for a DP comprising these food groups besides others (IRRpooled per 1 SD = 1.104, 95% CI 1.059-1.151). Although heterogeneity was present (I2 = 85%), IRR exceeded 1 in 18 of the 20 meta-analyzed studies. Original DPs associated with lower T2D risk were not confirmed. Instead, a healthy DP (HDP1) was associated with higher T2D risk (IRRpooled per 1 SD = 1.057, 95% CI 1.027-1.088). CONCLUSION: Our findings from various cohorts revealed positive associations for several DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, adding to the evidence-base that links DPs to higher T2D risk. However, no inverse DP-T2D associations were confirmed.

Published
2022

2. Genomic analysis of diet composition finds novel loci and associations with health and lifestyle.

Author

Meddens, S Fleur W, Meddens, S Fleur W, de Vlaming, Ronald, Bowers, Peter, Burik, Casper AP, Linnér, Richard Karlsson, Lee, Chanwook, Okbay, Aysu, Turley, Patrick, Rietveld, Cornelius A, Fontana, Mark Alan, Ghanbari, Mohsen, Imamura, Fumiaki, McMahon, George, van der Most, Peter J, Voortman, Trudy, Wade, Kaitlin H, Anderson, Emma L, Braun, Kim VE, Emmett, Pauline M, Esko, Tonũ, Gonzalez, Juan R, Kiefte-de Jong, Jessica C, Langenberg, Claudia, Luan, Jian'an, Muka, Taulant, Ring, Susan, Rivadeneira, Fernando, Snieder, Harold, van Rooij, Frank JA, Wolffenbuttel, Bruce HR, 23andMe Research Team, EPIC- InterAct Consortium, Lifelines Cohort Study, Smith, George Davey, Franco, Oscar H, Forouhi, Nita G, Ikram, M Arfan, Uitterlinden, Andre G, van Vliet-Ostaptchouk, Jana V, Wareham, Nick J, Cesarini, David, Harden, K Paige, Lee, James J, Benjamin, Daniel J, Chow, Carson C, Koellinger, Philipp D, Meddens, S Fleur W, Meddens, S Fleur W, de Vlaming, Ronald, Bowers, Peter, Burik, Casper AP, Linnér, Richard Karlsson, Lee, Chanwook, Okbay, Aysu, Turley, Patrick, Rietveld, Cornelius A, Fontana, Mark Alan, Ghanbari, Mohsen, Imamura, Fumiaki, McMahon, George, van der Most, Peter J, Voortman, Trudy, Wade, Kaitlin H, Anderson, Emma L, Braun, Kim VE, Emmett, Pauline M, Esko, Tonũ, Gonzalez, Juan R, Kiefte-de Jong, Jessica C, Langenberg, Claudia, Luan, Jian'an, Muka, Taulant, Ring, Susan, Rivadeneira, Fernando, Snieder, Harold, van Rooij, Frank JA, Wolffenbuttel, Bruce HR, 23andMe Research Team, EPIC- InterAct Consortium, Lifelines Cohort Study, Smith, George Davey, Franco, Oscar H, Forouhi, Nita G, Ikram, M Arfan, Uitterlinden, Andre G, van Vliet-Ostaptchouk, Jana V, Wareham, Nick J, Cesarini, David, Harden, K Paige, Lee, James J, Benjamin, Daniel J, Chow, Carson C, and Koellinger, Philipp D

Abstract

We conducted genome-wide association studies (GWAS) of relative intake from the macronutrients fat, protein, carbohydrates, and sugar in over 235,000 individuals of European ancestries. We identified 21 unique, approximately independent lead SNPs. Fourteen lead SNPs are uniquely associated with one macronutrient at genome-wide significance (P < 5 × 10-8), while five of the 21 lead SNPs reach suggestive significance (P < 1 × 10-5) for at least one other macronutrient. While the phenotypes are genetically correlated, each phenotype carries a partially unique genetic architecture. Relative protein intake exhibits the strongest relationships with poor health, including positive genetic associations with obesity, type 2 diabetes, and heart disease (rg ≈ 0.15-0.5). In contrast, relative carbohydrate and sugar intake have negative genetic correlations with waist circumference, waist-hip ratio, and neighborhood deprivation (|rg| ≈ 0.1-0.3) and positive genetic correlations with physical activity (rg ≈ 0.1 and 0.2). Relative fat intake has no consistent pattern of genetic correlations with poor health but has a negative genetic correlation with educational attainment (rg ≈-0.1). Although our analyses do not allow us to draw causal conclusions, we find no evidence of negative health consequences associated with relative carbohydrate, sugar, or fat intake. However, our results are consistent with the hypothesis that relative protein intake plays a role in the etiology of metabolic dysfunction.

Published
2021

3. Genomic analysis of diet composition finds novel loci and associations with health and lifestyle.

Author

Meddens, S Fleur W, Meddens, S Fleur W, de Vlaming, Ronald, Bowers, Peter, Burik, Casper AP, Linnér, Richard Karlsson, Lee, Chanwook, Okbay, Aysu, Turley, Patrick, Rietveld, Cornelius A, Fontana, Mark Alan, Ghanbari, Mohsen, Imamura, Fumiaki, McMahon, George, van der Most, Peter J, Voortman, Trudy, Wade, Kaitlin H, Anderson, Emma L, Braun, Kim VE, Emmett, Pauline M, Esko, Tonũ, Gonzalez, Juan R, Kiefte-de Jong, Jessica C, Langenberg, Claudia, Luan, Jian'an, Muka, Taulant, Ring, Susan, Rivadeneira, Fernando, Snieder, Harold, van Rooij, Frank JA, Wolffenbuttel, Bruce HR, 23andMe Research Team, EPIC- InterAct Consortium, Lifelines Cohort Study, Smith, George Davey, Franco, Oscar H, Forouhi, Nita G, Ikram, M Arfan, Uitterlinden, Andre G, van Vliet-Ostaptchouk, Jana V, Wareham, Nick J, Cesarini, David, Harden, K Paige, Lee, James J, Benjamin, Daniel J, Chow, Carson C, Koellinger, Philipp D, Meddens, S Fleur W, Meddens, S Fleur W, de Vlaming, Ronald, Bowers, Peter, Burik, Casper AP, Linnér, Richard Karlsson, Lee, Chanwook, Okbay, Aysu, Turley, Patrick, Rietveld, Cornelius A, Fontana, Mark Alan, Ghanbari, Mohsen, Imamura, Fumiaki, McMahon, George, van der Most, Peter J, Voortman, Trudy, Wade, Kaitlin H, Anderson, Emma L, Braun, Kim VE, Emmett, Pauline M, Esko, Tonũ, Gonzalez, Juan R, Kiefte-de Jong, Jessica C, Langenberg, Claudia, Luan, Jian'an, Muka, Taulant, Ring, Susan, Rivadeneira, Fernando, Snieder, Harold, van Rooij, Frank JA, Wolffenbuttel, Bruce HR, 23andMe Research Team, EPIC- InterAct Consortium, Lifelines Cohort Study, Smith, George Davey, Franco, Oscar H, Forouhi, Nita G, Ikram, M Arfan, Uitterlinden, Andre G, van Vliet-Ostaptchouk, Jana V, Wareham, Nick J, Cesarini, David, Harden, K Paige, Lee, James J, Benjamin, Daniel J, Chow, Carson C, and Koellinger, Philipp D

Abstract

We conducted genome-wide association studies (GWAS) of relative intake from the macronutrients fat, protein, carbohydrates, and sugar in over 235,000 individuals of European ancestries. We identified 21 unique, approximately independent lead SNPs. Fourteen lead SNPs are uniquely associated with one macronutrient at genome-wide significance (P < 5 × 10-8), while five of the 21 lead SNPs reach suggestive significance (P < 1 × 10-5) for at least one other macronutrient. While the phenotypes are genetically correlated, each phenotype carries a partially unique genetic architecture. Relative protein intake exhibits the strongest relationships with poor health, including positive genetic associations with obesity, type 2 diabetes, and heart disease (rg ≈ 0.15-0.5). In contrast, relative carbohydrate and sugar intake have negative genetic correlations with waist circumference, waist-hip ratio, and neighborhood deprivation (|rg| ≈ 0.1-0.3) and positive genetic correlations with physical activity (rg ≈ 0.1 and 0.2). Relative fat intake has no consistent pattern of genetic correlations with poor health but has a negative genetic correlation with educational attainment (rg ≈-0.1). Although our analyses do not allow us to draw causal conclusions, we find no evidence of negative health consequences associated with relative carbohydrate, sugar, or fat intake. However, our results are consistent with the hypothesis that relative protein intake plays a role in the etiology of metabolic dysfunction.

Published
2021

4. Genomic analysis of diet composition finds novel loci and associations with health and lifestyle.

Author

Meddens, S Fleur W, Meddens, S Fleur W, de Vlaming, Ronald, Bowers, Peter, Burik, Casper AP, Linnér, Richard Karlsson, Lee, Chanwook, Okbay, Aysu, Turley, Patrick, Rietveld, Cornelius A, Fontana, Mark Alan, Ghanbari, Mohsen, Imamura, Fumiaki, McMahon, George, van der Most, Peter J, Voortman, Trudy, Wade, Kaitlin H, Anderson, Emma L, Braun, Kim VE, Emmett, Pauline M, Esko, Tonũ, Gonzalez, Juan R, Kiefte-de Jong, Jessica C, Langenberg, Claudia, Luan, Jian'an, Muka, Taulant, Ring, Susan, Rivadeneira, Fernando, Snieder, Harold, van Rooij, Frank JA, Wolffenbuttel, Bruce HR, 23andMe Research Team, EPIC- InterAct Consortium, Lifelines Cohort Study, Smith, George Davey, Franco, Oscar H, Forouhi, Nita G, Ikram, M Arfan, Uitterlinden, Andre G, van Vliet-Ostaptchouk, Jana V, Wareham, Nick J, Cesarini, David, Harden, K Paige, Lee, James J, Benjamin, Daniel J, Chow, Carson C, Koellinger, Philipp D, Meddens, S Fleur W, Meddens, S Fleur W, de Vlaming, Ronald, Bowers, Peter, Burik, Casper AP, Linnér, Richard Karlsson, Lee, Chanwook, Okbay, Aysu, Turley, Patrick, Rietveld, Cornelius A, Fontana, Mark Alan, Ghanbari, Mohsen, Imamura, Fumiaki, McMahon, George, van der Most, Peter J, Voortman, Trudy, Wade, Kaitlin H, Anderson, Emma L, Braun, Kim VE, Emmett, Pauline M, Esko, Tonũ, Gonzalez, Juan R, Kiefte-de Jong, Jessica C, Langenberg, Claudia, Luan, Jian'an, Muka, Taulant, Ring, Susan, Rivadeneira, Fernando, Snieder, Harold, van Rooij, Frank JA, Wolffenbuttel, Bruce HR, 23andMe Research Team, EPIC- InterAct Consortium, Lifelines Cohort Study, Smith, George Davey, Franco, Oscar H, Forouhi, Nita G, Ikram, M Arfan, Uitterlinden, Andre G, van Vliet-Ostaptchouk, Jana V, Wareham, Nick J, Cesarini, David, Harden, K Paige, Lee, James J, Benjamin, Daniel J, Chow, Carson C, and Koellinger, Philipp D

Abstract

We conducted genome-wide association studies (GWAS) of relative intake from the macronutrients fat, protein, carbohydrates, and sugar in over 235,000 individuals of European ancestries. We identified 21 unique, approximately independent lead SNPs. Fourteen lead SNPs are uniquely associated with one macronutrient at genome-wide significance (P < 5 × 10-8), while five of the 21 lead SNPs reach suggestive significance (P < 1 × 10-5) for at least one other macronutrient. While the phenotypes are genetically correlated, each phenotype carries a partially unique genetic architecture. Relative protein intake exhibits the strongest relationships with poor health, including positive genetic associations with obesity, type 2 diabetes, and heart disease (rg ≈ 0.15-0.5). In contrast, relative carbohydrate and sugar intake have negative genetic correlations with waist circumference, waist-hip ratio, and neighborhood deprivation (|rg| ≈ 0.1-0.3) and positive genetic correlations with physical activity (rg ≈ 0.1 and 0.2). Relative fat intake has no consistent pattern of genetic correlations with poor health but has a negative genetic correlation with educational attainment (rg ≈-0.1). Although our analyses do not allow us to draw causal conclusions, we find no evidence of negative health consequences associated with relative carbohydrate, sugar, or fat intake. However, our results are consistent with the hypothesis that relative protein intake plays a role in the etiology of metabolic dysfunction.

Published
2021

9. Publisher Correction : Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Author

Turcot, Valérie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G.D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C.Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Gonçalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bots, Michiel L., Ruijter, Hester M., Ikram, M. Arfan, Kahn, René S., Ophoff, Roel A., Pasterkamp, Gerard, van Setten, Jessica, CHD Exome+ Consortium, EPIC-CVD Consortium, ExomeBP Consortium, Global Lipids Genetic Consortium, GoT2D Genes Consortium, EPIC InterAct Consortium, INTERVAL Study, ReproGen Consortium, T2D-Genes Consortium, The MAGIC Investigators, Understanding Society Scientific Group, Turcot, Valérie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G.D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C.Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Gonçalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bots, Michiel L., Ruijter, Hester M., Ikram, M. Arfan, Kahn, René S., Ophoff, Roel A., Pasterkamp, Gerard, van Setten, Jessica, CHD Exome+ Consortium, EPIC-CVD Consortium, ExomeBP Consortium, Global Lipids Genetic Consortium, GoT2D Genes Consortium, EPIC InterAct Consortium, INTERVAL Study, ReproGen Consortium, T2D-Genes Consortium, The MAGIC Investigators, and Understanding Society Scientific Group

Published
2018

10. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Author

CHD Exome+ Consortium, EPIC-CVD Consortium, ExomeBP Consortium, Global Lipids Genetic Consortium, GoT2D Genes Consortium, EPIC-InterAct Consortium, INTERVAL Study, ReproGen Consortium, T2D-Genes Consortium, MAGIC Investigators, Understanding Society Scientific Group, CHD Exome+ Consortium, EPIC-CVD Consortium, ExomeBP Consortium, Global Lipids Genetic Consortium, GoT2D Genes Consortium, EPIC-InterAct Consortium, INTERVAL Study, ReproGen Consortium, T2D-Genes Consortium, MAGIC Investigators, and Understanding Society Scientific Group

Abstract

In the published version of this paper, the name of author Emanuele Di Angelantonio was misspelled. This error has now been corrected in the HTML and PDF versions of the article.

Published
2018
Full Text
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11. Publisher Correction : Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Author

Turcot, Valérie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G.D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C.Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Gonçalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bots, Michiel L., Ruijter, Hester M., Ikram, M. Arfan, Kahn, René S., Ophoff, Roel A., Pasterkamp, Gerard, van Setten, Jessica, CHD Exome+ Consortium, EPIC-CVD Consortium, ExomeBP Consortium, Global Lipids Genetic Consortium, GoT2D Genes Consortium, EPIC InterAct Consortium, INTERVAL Study, ReproGen Consortium, T2D-Genes Consortium, The MAGIC Investigators, Understanding Society Scientific Group, Turcot, Valérie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G.D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C.Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Gonçalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bots, Michiel L., Ruijter, Hester M., Ikram, M. Arfan, Kahn, René S., Ophoff, Roel A., Pasterkamp, Gerard, van Setten, Jessica, CHD Exome+ Consortium, EPIC-CVD Consortium, ExomeBP Consortium, Global Lipids Genetic Consortium, GoT2D Genes Consortium, EPIC InterAct Consortium, INTERVAL Study, ReproGen Consortium, T2D-Genes Consortium, The MAGIC Investigators, and Understanding Society Scientific Group

Published
2018

12. Publisher Correction : Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Author

Turcot, Valérie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G.D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C.Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Gonçalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bots, Michiel L., Ruijter, Hester M., Ikram, M. Arfan, Kahn, René S., Ophoff, Roel A., Pasterkamp, Gerard, van Setten, Jessica, CHD Exome+ Consortium, EPIC-CVD Consortium, ExomeBP Consortium, Global Lipids Genetic Consortium, GoT2D Genes Consortium, EPIC InterAct Consortium, INTERVAL Study, ReproGen Consortium, T2D-Genes Consortium, The MAGIC Investigators, Understanding Society Scientific Group, Turcot, Valérie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G.D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C.Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Gonçalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bots, Michiel L., Ruijter, Hester M., Ikram, M. Arfan, Kahn, René S., Ophoff, Roel A., Pasterkamp, Gerard, van Setten, Jessica, CHD Exome+ Consortium, EPIC-CVD Consortium, ExomeBP Consortium, Global Lipids Genetic Consortium, GoT2D Genes Consortium, EPIC InterAct Consortium, INTERVAL Study, ReproGen Consortium, T2D-Genes Consortium, The MAGIC Investigators, and Understanding Society Scientific Group

Published
2018

13. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Author

Aios en Stafsecr. Cardiologie, Circulatory Health, Cardiovasculaire Epi Team 5, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Experimentele Afd. Cardiologie 1, Cardiovasculaire Epi Team 7, ZL Cerebrovasculaire Ziekten Medisch, Onderzoeksgroep 11, Brain, Onderzoek, CDL Cluster Onderzoek en Onderwijs, Onderzoek Precision medicine, Turcot, Valérie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G.D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C.Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Gonçalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bots, Michiel L., Ruijter, Hester M., Ikram, M. Arfan, Kahn, René S., Ophoff, Roel A., Pasterkamp, Gerard, van Setten, Jessica, CHD Exome+ Consortium, EPIC-CVD Consortium, ExomeBP Consortium, Global Lipids Genetic Consortium, GoT2D Genes Consortium, EPIC InterAct Consortium, INTERVAL Study, ReproGen Consortium, T2D-GENES Consortium, The MAGIC Investigators, Understanding Society Scientific Group, Aios en Stafsecr. Cardiologie, Circulatory Health, Cardiovasculaire Epi Team 5, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Experimentele Afd. Cardiologie 1, Cardiovasculaire Epi Team 7, ZL Cerebrovasculaire Ziekten Medisch, Onderzoeksgroep 11, Brain, Onderzoek, CDL Cluster Onderzoek en Onderwijs, Onderzoek Precision medicine, Turcot, Valérie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G.D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C.Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Gonçalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bots, Michiel L., Ruijter, Hester M., Ikram, M. Arfan, Kahn, René S., Ophoff, Roel A., Pasterkamp, Gerard, van Setten, Jessica, CHD Exome+ Consortium, EPIC-CVD Consortium, ExomeBP Consortium, Global Lipids Genetic Consortium, GoT2D Genes Consortium, EPIC InterAct Consortium, INTERVAL Study, ReproGen Consortium, T2D-GENES Consortium, The MAGIC Investigators, and Understanding Society Scientific Group

Published
2018

14. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Author

CHD Exome+ Consortium, EPIC-CVD Consortium, ExomeBP Consortium, Global Lipids Genetic Consortium, GoT2D Genes Consortium, EPIC-InterAct Consortium, INTERVAL Study, ReproGen Consortium, T2D-Genes Consortium, MAGIC Investigators, Understanding Society Scientific Group, CHD Exome+ Consortium, EPIC-CVD Consortium, ExomeBP Consortium, Global Lipids Genetic Consortium, GoT2D Genes Consortium, EPIC-InterAct Consortium, INTERVAL Study, ReproGen Consortium, T2D-Genes Consortium, MAGIC Investigators, and Understanding Society Scientific Group

Abstract

In the published version of this paper, the name of author Emanuele Di Angelantonio was misspelled. This error has now been corrected in the HTML and PDF versions of the article.

Published
2018
Full Text
View/download PDF

15. Rare and low-frequency coding variants alter human adult height

Author

Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas G D, Ng, Maggie C Y, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Banas, Bernhard, Bang, Lia E, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boeing, Heiner, Boerwinkle, Eric, de Groot, Mark C H, EPIC-InterAct Consortium, Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas G D, Ng, Maggie C Y, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Banas, Bernhard, Bang, Lia E, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boeing, Heiner, Boerwinkle, Eric, de Groot, Mark C H, and EPIC-InterAct Consortium

Abstract

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

Published
2017

16. Rare and low-frequency coding variants alter human adult height

Author

Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas G D, Ng, Maggie C Y, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Bots, Michiel L, de Bakker, Paul I W, de Borst, Gert J, de Groot, Mark C H, Kahn, René S, Ophoff, RA, Pasterkamp, Gerard, van der Laan, Sander W, van Setten, Jessica, EPIC-InterAct Consortium, Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas G D, Ng, Maggie C Y, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Bots, Michiel L, de Bakker, Paul I W, de Borst, Gert J, de Groot, Mark C H, Kahn, René S, Ophoff, RA, Pasterkamp, Gerard, van der Laan, Sander W, van Setten, Jessica, and EPIC-InterAct Consortium

Published
2017

17. Rare and low-frequency coding variants alter human adult height

Author

Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas G D, Ng, Maggie C Y, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Bots, Michiel L, de Bakker, Paul I W, de Borst, Gert J, de Groot, Mark C H, Kahn, René S, Ophoff, RA, Pasterkamp, Gerard, van der Laan, Sander W, van Setten, Jessica, EPIC-InterAct Consortium, Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas G D, Ng, Maggie C Y, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Bots, Michiel L, de Bakker, Paul I W, de Borst, Gert J, de Groot, Mark C H, Kahn, René S, Ophoff, RA, Pasterkamp, Gerard, van der Laan, Sander W, van Setten, Jessica, and EPIC-InterAct Consortium

Published
2017

18. Rare and low-frequency coding variants alter human adult height

Author

Pharmacoepidemiology and Clinical Pharmacology, Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas G D, Ng, Maggie C Y, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Banas, Bernhard, Bang, Lia E, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boeing, Heiner, Boerwinkle, Eric, de Groot, Mark C H, EPIC-InterAct Consortium, Pharmacoepidemiology and Clinical Pharmacology, Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas G D, Ng, Maggie C Y, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Banas, Bernhard, Bang, Lia E, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boeing, Heiner, Boerwinkle, Eric, de Groot, Mark C H, and EPIC-InterAct Consortium

Published
2017

19. Rare and low-frequency coding variants alter human adult height

Author

Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas G D, Ng, Maggie C Y, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Bots, Michiel L, de Bakker, Paul I W, de Borst, Gert J, de Groot, Mark C H, Kahn, René S, Ophoff, RA, Pasterkamp, Gerard, van der Laan, Sander W, van Setten, Jessica, EPIC-InterAct Consortium, Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas G D, Ng, Maggie C Y, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Bots, Michiel L, de Bakker, Paul I W, de Borst, Gert J, de Groot, Mark C H, Kahn, René S, Ophoff, RA, Pasterkamp, Gerard, van der Laan, Sander W, van Setten, Jessica, and EPIC-InterAct Consortium

Published
2017

20. Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance.

Author

Lotta, Luca A, Lotta, Luca A, Gulati, Pawan, Day, Felix R, Payne, Felicity, Ongen, Halit, van de Bunt, Martijn, Gaulton, Kyle J, Eicher, John D, Sharp, Stephen J, Luan, Jian'an, De Lucia Rolfe, Emanuella, Stewart, Isobel D, Wheeler, Eleanor, Willems, Sara M, Adams, Claire, Yaghootkar, Hanieh, EPIC-InterAct Consortium, Cambridge FPLD1 Consortium, Forouhi, Nita G, Khaw, Kay-Tee, Johnson, Andrew D, Semple, Robert K, Frayling, Timothy, Perry, John RB, Dermitzakis, Emmanouil, McCarthy, Mark I, Barroso, Inês, Wareham, Nicholas J, Savage, David B, Langenberg, Claudia, O'Rahilly, Stephen, Scott, Robert A, Lotta, Luca A, Lotta, Luca A, Gulati, Pawan, Day, Felix R, Payne, Felicity, Ongen, Halit, van de Bunt, Martijn, Gaulton, Kyle J, Eicher, John D, Sharp, Stephen J, Luan, Jian'an, De Lucia Rolfe, Emanuella, Stewart, Isobel D, Wheeler, Eleanor, Willems, Sara M, Adams, Claire, Yaghootkar, Hanieh, EPIC-InterAct Consortium, Cambridge FPLD1 Consortium, Forouhi, Nita G, Khaw, Kay-Tee, Johnson, Andrew D, Semple, Robert K, Frayling, Timothy, Perry, John RB, Dermitzakis, Emmanouil, McCarthy, Mark I, Barroso, Inês, Wareham, Nicholas J, Savage, David B, Langenberg, Claudia, O'Rahilly, Stephen, and Scott, Robert A

Abstract

Insulin resistance is a key mediator of obesity-related cardiometabolic disease, yet the mechanisms underlying this link remain obscure. Using an integrative genomic approach, we identify 53 genomic regions associated with insulin resistance phenotypes (higher fasting insulin levels adjusted for BMI, lower HDL cholesterol levels and higher triglyceride levels) and provide evidence that their link with higher cardiometabolic risk is underpinned by an association with lower adipose mass in peripheral compartments. Using these 53 loci, we show a polygenic contribution to familial partial lipodystrophy type 1, a severe form of insulin resistance, and highlight shared molecular mechanisms in common/mild and rare/severe insulin resistance. Population-level genetic analyses combined with experiments in cellular models implicate CCDC92, DNAH10 and L3MBTL3 as previously unrecognized molecules influencing adipocyte differentiation. Our findings support the notion that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.

Published
2017

21. Rare and low-frequency coding variants alter human adult height

Author

Pharmacoepidemiology and Clinical Pharmacology, Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas G D, Ng, Maggie C Y, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Banas, Bernhard, Bang, Lia E, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boeing, Heiner, Boerwinkle, Eric, de Groot, Mark C H, EPIC-InterAct Consortium, Pharmacoepidemiology and Clinical Pharmacology, Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas G D, Ng, Maggie C Y, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Banas, Bernhard, Bang, Lia E, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boeing, Heiner, Boerwinkle, Eric, de Groot, Mark C H, and EPIC-InterAct Consortium

Published
2017

22. Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease.

Author

Zhao, Wei, Zhao, Wei, Rasheed, Asif, Tikkanen, Emmi, Lee, Jung-Jin, Butterworth, Adam S, Howson, Joanna MM, Assimes, Themistocles L, Chowdhury, Rajiv, Orho-Melander, Marju, Damrauer, Scott, Small, Aeron, Asma, Senay, Imamura, Minako, Yamauch, Toshimasa, Chambers, John C, Chen, Peng, Sapkota, Bishwa R, Shah, Nabi, Jabeen, Sehrish, Surendran, Praveen, Lu, Yingchang, Zhang, Weihua, Imran, Atif, Abbas, Shahid, Majeed, Faisal, Trindade, Kevin, Qamar, Nadeem, Mallick, Nadeem Hayyat, Yaqoob, Zia, Saghir, Tahir, Rizvi, Syed Nadeem Hasan, Memon, Anis, Rasheed, Syed Zahed, Memon, Fazal-Ur-Rehman, Mehmood, Khalid, Ahmed, Naveeduddin, Qureshi, Irshad Hussain, Tanveer-Us-Salam, Iqbal, Wasim, Malik, Uzma, Mehra, Narinder, Kuo, Jane Z, Sheu, Wayne H-H, Guo, Xiuqing, Hsiung, Chao A, Juang, Jyh-Ming J, Taylor, Kent D, Hung, Yi-Jen, Lee, Wen-Jane, Quertermous, Thomas, Lee, I-Te, Hsu, Chih-Cheng, Bottinger, Erwin P, Ralhan, Sarju, Teo, Yik Ying, Wang, Tzung-Dau, Alam, Dewan S, Di Angelantonio, Emanuele, Epstein, Steve, Nielsen, Sune F, Nordestgaard, Børge G, Tybjaerg-Hansen, Anne, Young, Robin, CHD Exome+ Consortium, Benn, Marianne, Frikke-Schmidt, Ruth, Kamstrup, Pia R, EPIC-CVD Consortium, EPIC-Interact Consortium, Michigan Biobank, Jukema, J Wouter, Sattar, Naveed, Smit, Roelof, Chung, Ren-Hua, Liang, Kae-Woei, Anand, Sonia, Sanghera, Dharambir K, Ripatti, Samuli, Loos, Ruth JF, Kooner, Jaspal S, Tai, E Shyong, Rotter, Jerome I, Chen, Yii-Der Ida, Frossard, Philippe, Maeda, Shiro, Kadowaki, Takashi, Reilly, Muredach, Pare, Guillaume, Melander, Olle, Salomaa, Veikko, Rader, Daniel J, Danesh, John, Voight, Benjamin F, Saleheen, Danish, Zhao, Wei, Zhao, Wei, Rasheed, Asif, Tikkanen, Emmi, Lee, Jung-Jin, Butterworth, Adam S, Howson, Joanna MM, Assimes, Themistocles L, Chowdhury, Rajiv, Orho-Melander, Marju, Damrauer, Scott, Small, Aeron, Asma, Senay, Imamura, Minako, Yamauch, Toshimasa, Chambers, John C, Chen, Peng, Sapkota, Bishwa R, Shah, Nabi, Jabeen, Sehrish, Surendran, Praveen, Lu, Yingchang, Zhang, Weihua, Imran, Atif, Abbas, Shahid, Majeed, Faisal, Trindade, Kevin, Qamar, Nadeem, Mallick, Nadeem Hayyat, Yaqoob, Zia, Saghir, Tahir, Rizvi, Syed Nadeem Hasan, Memon, Anis, Rasheed, Syed Zahed, Memon, Fazal-Ur-Rehman, Mehmood, Khalid, Ahmed, Naveeduddin, Qureshi, Irshad Hussain, Tanveer-Us-Salam, Iqbal, Wasim, Malik, Uzma, Mehra, Narinder, Kuo, Jane Z, Sheu, Wayne H-H, Guo, Xiuqing, Hsiung, Chao A, Juang, Jyh-Ming J, Taylor, Kent D, Hung, Yi-Jen, Lee, Wen-Jane, Quertermous, Thomas, Lee, I-Te, Hsu, Chih-Cheng, Bottinger, Erwin P, Ralhan, Sarju, Teo, Yik Ying, Wang, Tzung-Dau, Alam, Dewan S, Di Angelantonio, Emanuele, Epstein, Steve, Nielsen, Sune F, Nordestgaard, Børge G, Tybjaerg-Hansen, Anne, Young, Robin, CHD Exome+ Consortium, Benn, Marianne, Frikke-Schmidt, Ruth, Kamstrup, Pia R, EPIC-CVD Consortium, EPIC-Interact Consortium, Michigan Biobank, Jukema, J Wouter, Sattar, Naveed, Smit, Roelof, Chung, Ren-Hua, Liang, Kae-Woei, Anand, Sonia, Sanghera, Dharambir K, Ripatti, Samuli, Loos, Ruth JF, Kooner, Jaspal S, Tai, E Shyong, Rotter, Jerome I, Chen, Yii-Der Ida, Frossard, Philippe, Maeda, Shiro, Kadowaki, Takashi, Reilly, Muredach, Pare, Guillaume, Melander, Olle, Salomaa, Veikko, Rader, Daniel J, Danesh, John, Voight, Benjamin F, and Saleheen, Danish

Abstract

To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and 1 locus for CHD, including a new T2D association at a missense variant in HLA-DRB5 (odds ratio (OR) = 1.29). We show that genetically mediated increase in T2D risk also confers higher CHD risk. Joint T2D-CHD analysis identified eight variants-two of which are coding-where T2D and CHD associations appear to colocalize, including a new joint T2D-CHD association at the CCDC92 locus that also replicated for T2D. The variants associated with both outcomes implicate new pathways as well as targets of existing drugs, including icosapent ethyl and adipocyte fatty-acid-binding protein.

Published
2017

23. Rare and low-frequency coding variants alter human adult height

Author

Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas G D, Ng, Maggie C Y, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Banas, Bernhard, Bang, Lia E, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boeing, Heiner, Boerwinkle, Eric, Posthuma, Danielle, EPIC-InterAct Consortium, Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas G D, Ng, Maggie C Y, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Banas, Bernhard, Bang, Lia E, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boeing, Heiner, Boerwinkle, Eric, Posthuma, Danielle, and EPIC-InterAct Consortium

Abstract

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

Published
2017
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24. Rare and low-frequency coding variants alter human adult height

Author

Circulatory Health, Team Medisch, Cardiovasculaire Epi Team 5, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, CMM Groep Kaaij, Brain, Infection & Immunity, Zorgeenheid Vaatchirurgie Medisch, CDL Upod, Other research (not in main researchprogram), Onderzoek, CDL Cluster Onderzoek en Onderwijs, Experimentele Afd. Cardiologie 1, Onderzoek Precision medicine, Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas G D, Ng, Maggie C Y, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Bots, Michiel L, de Bakker, Paul I W, de Borst, Gert J, de Groot, Mark C H, Kahn, René S, Ophoff, RA, Pasterkamp, Gerard, van der Laan, Sander W, van Setten, Jessica, EPIC InterAct Consortium, Circulatory Health, Team Medisch, Cardiovasculaire Epi Team 5, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, CMM Groep Kaaij, Brain, Infection & Immunity, Zorgeenheid Vaatchirurgie Medisch, CDL Upod, Other research (not in main researchprogram), Onderzoek, CDL Cluster Onderzoek en Onderwijs, Experimentele Afd. Cardiologie 1, Onderzoek Precision medicine, Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas G D, Ng, Maggie C Y, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Bots, Michiel L, de Bakker, Paul I W, de Borst, Gert J, de Groot, Mark C H, Kahn, René S, Ophoff, RA, Pasterkamp, Gerard, van der Laan, Sander W, van Setten, Jessica, and EPIC InterAct Consortium

Published
2017

25. Rare and low-frequency coding variants alter human adult height

Author

Pharmacoepidemiology and Clinical Pharmacology, Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas G D, Ng, Maggie C Y, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Banas, Bernhard, Bang, Lia E, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boeing, Heiner, Boerwinkle, Eric, de Groot, Mark C H, EPIC-InterAct Consortium, Pharmacoepidemiology and Clinical Pharmacology, Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas G D, Ng, Maggie C Y, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Banas, Bernhard, Bang, Lia E, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boeing, Heiner, Boerwinkle, Eric, de Groot, Mark C H, and EPIC-InterAct Consortium

Published
2017

26. Correction: Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.

Author

Graff, M., Scott, R.A., Justice, A.E., Young, K.L., Feitosa, M.F., Barata, L., Winkler, T.W., Chu, A.Y., Mahajan, A., Hadley, D., Xue, L., Workalemahu, T., Heard-Costa, N.L., den Hoed, M., Ahluwalia, T.S., Qi, Q., Ngwa, J.S., Renström, F., Quaye, L., Eicher, J.D., Hayes, J.E., Cornelis, M., Kutalik, Z., Lim, E., Luan, J., Huffman, J.E., Zhang, W., Zhao, W., Griffin, P.J., Haller, T., Ahmad, S., Marques-Vidal, P.M., Bien, S., Yengo, L., Teumer, A., Smith, A.V., Kumari, M., Harder, M.N., Justesen, J.M., Kleber, M.E., Hollensted, M., Lohman, K., Rivera, N.V., Whitfield, J.B., Zhao, J.H., Stringham, H.M., Lyytikäinen, L.P., Huppertz, C., Willemsen, G., Peyrot, W.J., Wu, Y., Kristiansson, K., Demirkan, A., Fornage, M., Hassinen, M., Bielak, L.F., Cadby, G., Tanaka, T., Mägi, R., van der Most, P.J., Jackson, A.U., Bragg-Gresham, J.L., Vitart, V., Marten, J., Navarro, P., Bellis, C., Pasko, D., Johansson, Å., Snitker, S., Cheng, Y.C., Eriksson, J., Lim, U., Aadahl, M., Adair, L.S., Amin, N., Balkau, B., Auvinen, J., Beilby, J., Bergman, R.N., Bergmann, S., Bertoni, A.G., Blangero, J., Bonnefond, A., Bonnycastle, L.L., Borja, J.B., Brage, S., Busonero, F., Buyske, S., Campbell, H., Chines, P.S., Collins, F.S., Corre, T., Smith, G.D., Delgado, G.E., Dueker, N., Dörr, M., Ebeling, T., Eiriksdottir, G., Esko, T., Faul, J.D., Fu, M., Færch, K., Gieger, C., Gläser, S., Gong, J., Gordon-Larsen, P., Grallert, H., Grammer, T.B., Grarup, N., van Grootheest, G., Harald, K., Hastie, N.D., Havulinna, A.S., Hernandez, D., Hindorff, L., Hocking, L.J., Holmens, O.L., Holzapfel, C., Hottenga, J.J., Huang, J., Huang, T., Hui, J., Huth, C., Hutri-Kähönen, N., James, A.L., Jansson, J.O., Jhun, M.A., Juonala, M., Kinnunen, L., Koistinen, H.A., Kolcic, I., Komulainen, P., Kuusisto, J., Kvaløy, K., Kähönen, M., Lakka, T.A., Launer, L.J., Lehne, B., Lindgren, C.M., Lorentzon, M., Luben, R., Marre, M., Milaneschi, Y., Monda, K.L., Montgomery, G.W., De Moor, MHM, Mulas, A., Müller-Nurasyid, M., Musk, A.W., Männikkö, R., Männistö, S., Narisu, N., Nauck, M., Nettleton, J.A., Nolte, I.M., Oldehinkel, A.J., Olden, M., Ong, K.K., Padmanabhan, S., Paternoster, L., Perez, J., Perola, M., Peters, A., Peters, U., Peyser, P.A., Prokopenko, I., Puolijoki, H., Raitakari, O.T., Rankinen, T., Rasmussen-Torvik, L.J., Rawal, R., Ridker, P.M., Rose, L.M., Rudan, I., Sarti, C., Sarzynski, M.A., Savonen, K., Scott, W.R., Sanna, S., Shuldiner, A.R., Sidney, S., Silbernagel, G., Smith, B.H., Smith, J.A., Snieder, H., Stančáková, A., Sternfeld, B., Swift, A.J., Tammelin, T., Tan, S.T., Thorand, B., Thuillier, D., Vandenput, L., Vestergaard, H., van Vliet-Ostaptchouk, J.V., Vohl, M.C., Völker, U., Waeber, G., Walker, M., Wild, S., Wong, A., Wright, A.F., Zillikens, M.C., Zubair, N., Haiman, C.A., Lemarchand, L., Gyllensten, U., Ohlsson, C., Hofman, A., Rivadeneira, F., Uitterlinden, A.G., Pérusse, L., Wilson, J.F., Hayward, C., Polasek, O., Cucca, F., Hveem, K., Hartman, C.A., Tönjes, A., Bandinelli, S., Palmer, L.J., Kardia, SLR, Rauramaa, R., Sørensen, TIA, Tuomilehto, J., Salomaa, V., Penninx, BWJH, de Geus, EJC, Boomsma, D.I., Lehtimäki, T., Mangino, M., Laakso, M., Bouchard, C., Martin, N.G., Kuh, D., Liu, Y., Linneberg, A., März, W., Strauch, K., Kivimäki, M., Harris, T.B., Gudnason, V., Völzke, H., Qi, L., Järvelin, M.R., Chambers, J.C., Kooner, J.S., Froguel, P., Kooperberg, C., Vollenweider, P., Hallmans, G., Hansen, T., Pedersen, O., Metspalu, A., Wareham, N.J., Langenberg, C., Weir, D.R., Porteous, D.J., Boerwinkle, E., Chasman, D.I., CHARGE, Consortium, EPIC-InterAct, Consortium, PAGE, Consortium, Abecasis, G.R., Barroso, I., McCarthy, M.I., Frayling, T.M., O'Connell, J.R., van Duijn, C.M., Boehnke, M., Heid, I.M., Mohlke, K.L., Strachan, D.P., Fox, C.S., Liu, C.T., Hirschhorn, J.N., Klein, R.J., Johnson, A.D., Borecki, I.B., Franks, P.W., North, K.E., Cupples, L.A., Loos, RJF, Kilpeläinen, T.O., Graff, M., Scott, R.A., Justice, A.E., Young, K.L., Feitosa, M.F., Barata, L., Winkler, T.W., Chu, A.Y., Mahajan, A., Hadley, D., Xue, L., Workalemahu, T., Heard-Costa, N.L., den Hoed, M., Ahluwalia, T.S., Qi, Q., Ngwa, J.S., Renström, F., Quaye, L., Eicher, J.D., Hayes, J.E., Cornelis, M., Kutalik, Z., Lim, E., Luan, J., Huffman, J.E., Zhang, W., Zhao, W., Griffin, P.J., Haller, T., Ahmad, S., Marques-Vidal, P.M., Bien, S., Yengo, L., Teumer, A., Smith, A.V., Kumari, M., Harder, M.N., Justesen, J.M., Kleber, M.E., Hollensted, M., Lohman, K., Rivera, N.V., Whitfield, J.B., Zhao, J.H., Stringham, H.M., Lyytikäinen, L.P., Huppertz, C., Willemsen, G., Peyrot, W.J., Wu, Y., Kristiansson, K., Demirkan, A., Fornage, M., Hassinen, M., Bielak, L.F., Cadby, G., Tanaka, T., Mägi, R., van der Most, P.J., Jackson, A.U., Bragg-Gresham, J.L., Vitart, V., Marten, J., Navarro, P., Bellis, C., Pasko, D., Johansson, Å., Snitker, S., Cheng, Y.C., Eriksson, J., Lim, U., Aadahl, M., Adair, L.S., Amin, N., Balkau, B., Auvinen, J., Beilby, J., Bergman, R.N., Bergmann, S., Bertoni, A.G., Blangero, J., Bonnefond, A., Bonnycastle, L.L., Borja, J.B., Brage, S., Busonero, F., Buyske, S., Campbell, H., Chines, P.S., Collins, F.S., Corre, T., Smith, G.D., Delgado, G.E., Dueker, N., Dörr, M., Ebeling, T., Eiriksdottir, G., Esko, T., Faul, J.D., Fu, M., Færch, K., Gieger, C., Gläser, S., Gong, J., Gordon-Larsen, P., Grallert, H., Grammer, T.B., Grarup, N., van Grootheest, G., Harald, K., Hastie, N.D., Havulinna, A.S., Hernandez, D., Hindorff, L., Hocking, L.J., Holmens, O.L., Holzapfel, C., Hottenga, J.J., Huang, J., Huang, T., Hui, J., Huth, C., Hutri-Kähönen, N., James, A.L., Jansson, J.O., Jhun, M.A., Juonala, M., Kinnunen, L., Koistinen, H.A., Kolcic, I., Komulainen, P., Kuusisto, J., Kvaløy, K., Kähönen, M., Lakka, T.A., Launer, L.J., Lehne, B., Lindgren, C.M., Lorentzon, M., Luben, R., Marre, M., Milaneschi, Y., Monda, K.L., Montgomery, G.W., De Moor, MHM, Mulas, A., Müller-Nurasyid, M., Musk, A.W., Männikkö, R., Männistö, S., Narisu, N., Nauck, M., Nettleton, J.A., Nolte, I.M., Oldehinkel, A.J., Olden, M., Ong, K.K., Padmanabhan, S., Paternoster, L., Perez, J., Perola, M., Peters, A., Peters, U., Peyser, P.A., Prokopenko, I., Puolijoki, H., Raitakari, O.T., Rankinen, T., Rasmussen-Torvik, L.J., Rawal, R., Ridker, P.M., Rose, L.M., Rudan, I., Sarti, C., Sarzynski, M.A., Savonen, K., Scott, W.R., Sanna, S., Shuldiner, A.R., Sidney, S., Silbernagel, G., Smith, B.H., Smith, J.A., Snieder, H., Stančáková, A., Sternfeld, B., Swift, A.J., Tammelin, T., Tan, S.T., Thorand, B., Thuillier, D., Vandenput, L., Vestergaard, H., van Vliet-Ostaptchouk, J.V., Vohl, M.C., Völker, U., Waeber, G., Walker, M., Wild, S., Wong, A., Wright, A.F., Zillikens, M.C., Zubair, N., Haiman, C.A., Lemarchand, L., Gyllensten, U., Ohlsson, C., Hofman, A., Rivadeneira, F., Uitterlinden, A.G., Pérusse, L., Wilson, J.F., Hayward, C., Polasek, O., Cucca, F., Hveem, K., Hartman, C.A., Tönjes, A., Bandinelli, S., Palmer, L.J., Kardia, SLR, Rauramaa, R., Sørensen, TIA, Tuomilehto, J., Salomaa, V., Penninx, BWJH, de Geus, EJC, Boomsma, D.I., Lehtimäki, T., Mangino, M., Laakso, M., Bouchard, C., Martin, N.G., Kuh, D., Liu, Y., Linneberg, A., März, W., Strauch, K., Kivimäki, M., Harris, T.B., Gudnason, V., Völzke, H., Qi, L., Järvelin, M.R., Chambers, J.C., Kooner, J.S., Froguel, P., Kooperberg, C., Vollenweider, P., Hallmans, G., Hansen, T., Pedersen, O., Metspalu, A., Wareham, N.J., Langenberg, C., Weir, D.R., Porteous, D.J., Boerwinkle, E., Chasman, D.I., CHARGE, Consortium, EPIC-InterAct, Consortium, PAGE, Consortium, Abecasis, G.R., Barroso, I., McCarthy, M.I., Frayling, T.M., O'Connell, J.R., van Duijn, C.M., Boehnke, M., Heid, I.M., Mohlke, K.L., Strachan, D.P., Fox, C.S., Liu, C.T., Hirschhorn, J.N., Klein, R.J., Johnson, A.D., Borecki, I.B., Franks, P.W., North, K.E., Cupples, L.A., Loos, RJF, and Kilpeläinen, T.O.

Abstract

[This corrects the article DOI: 10.1371/journal.pgen.1006528.].

Published
2017

27. Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study.

Author

Østergaard, Søren D, Østergaard, Søren D, Mukherjee, Shubhabrata, Sharp, Stephen J, Proitsi, Petroula, Lotta, Luca A, Day, Felix, Perry, John RB, Boehme, Kevin L, Walter, Stefan, Kauwe, John S, Gibbons, Laura E, Alzheimer’s Disease Genetics Consortium, GERAD1 Consortium, EPIC-InterAct Consortium, Larson, Eric B, Powell, John F, Langenberg, Claudia, Crane, Paul K, Wareham, Nicholas J, Scott, Robert A, Østergaard, Søren D, Østergaard, Søren D, Mukherjee, Shubhabrata, Sharp, Stephen J, Proitsi, Petroula, Lotta, Luca A, Day, Felix, Perry, John RB, Boehme, Kevin L, Walter, Stefan, Kauwe, John S, Gibbons, Laura E, Alzheimer’s Disease Genetics Consortium, GERAD1 Consortium, EPIC-InterAct Consortium, Larson, Eric B, Powell, John F, Langenberg, Claudia, Crane, Paul K, Wareham, Nicholas J, and Scott, Robert A

Abstract

BackgroundPotentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD) and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR).Methods and findingsWe used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, NSNPs = 49), fasting glucose (NSNPs = 36), insulin resistance (NSNPs = 10), body mass index (BMI, NSNPs = 32), total cholesterol (NSNPs = 73), HDL-cholesterol (NSNPs = 71), LDL-cholesterol (NSNPs = 57), triglycerides (NSNPs = 39), systolic blood pressure (SBP, NSNPs = 24), smoking initiation (NSNPs = 1), smoking quantity (NSNPs = 3), university completion (NSNPs = 2), and years of education (NSNPs = 1). We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP-AD associations from the International Genomics of Alzheimer's Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62-0.91]; p = 3.4 × 10(-3)). Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10(-8)). Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51-0.89]; p = 6.5 × 10(-3)), although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28). We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1). Pote

Published
2015

28. Associations between Potentially Modifiable Risk Factors and Alzheimer Disease : A Mendelian Randomization Study

Author

Ostergaard, Soren D., Mukherjee, Shubhabrata, Sharp, Stephen J., Proitsi, Petroula, Lotta, Luca A., Day, Felix, Perry, John R. B., Boehme, Kevin L., Walter, Stefan, Kauwe, John S., Gibbons, Laura E., Larson, Eric B., Powell, John F., Langenberg, Claudia, Crane, Paul K., Wareham, Nicholas J., Scott, Robert A., Alzheimer's Dis Genetics, GERAD1 Consortium, EPIC-InterAct Consortium, van der Schouw, YT, Ostergaard, Soren D., Mukherjee, Shubhabrata, Sharp, Stephen J., Proitsi, Petroula, Lotta, Luca A., Day, Felix, Perry, John R. B., Boehme, Kevin L., Walter, Stefan, Kauwe, John S., Gibbons, Laura E., Larson, Eric B., Powell, John F., Langenberg, Claudia, Crane, Paul K., Wareham, Nicholas J., Scott, Robert A., Alzheimer's Dis Genetics, GERAD1 Consortium, EPIC-InterAct Consortium, and van der Schouw, YT

Published
2015

29. Rare coding variants and X-linked loci associated with age at menarche

Author

Lunetta, Kathryn L., Day, Felix R., Sulem, Patrick, Ruth, Katherine S., Tung, Joyce Y., Hinds, David A., Esko, Tonu, Elks, Cathy E., Altmaier, Elisabeth, He, Chunyan, Huffman, Jennifer E., Mihailov, Evelin, Porcu, Eleonora, Robino, Antonietta, Rose, Lynda M., Schick, Ursula M., Stolk, Lisette, Teumer, Alexander, Thompson, Deborah J., Traglia, Michela, Wang, Carol A., Yerges-Armstrong, Laura M., Antoniou, Antonis C., Barbieri, Caterina, Coviello, Andrea D., Cucca, Francesco, Demerath, Ellen W., Dunning, Alison M., Gandin, Ilaria, Grove, Megan L., Gudbjartsson, Daniel F., Hocking, Lynne J., Hofman, Albert, Huang, Jinyan, Jackson, Rebecca D., Karasik, David, Kriebel, Jennifer, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Li, Xin, Luan, Jian'an, Maegi, Reedik, Morrison, Alanna C., Padmanabhan, Sandosh, Pirie, Ailith, Polasek, Ozren, Porteous, David, Reiner, Alex P., van der Schouw, Yvonne T., EPIC-InterAct Consortium, Generation Scotland, Lunetta, Kathryn L., Day, Felix R., Sulem, Patrick, Ruth, Katherine S., Tung, Joyce Y., Hinds, David A., Esko, Tonu, Elks, Cathy E., Altmaier, Elisabeth, He, Chunyan, Huffman, Jennifer E., Mihailov, Evelin, Porcu, Eleonora, Robino, Antonietta, Rose, Lynda M., Schick, Ursula M., Stolk, Lisette, Teumer, Alexander, Thompson, Deborah J., Traglia, Michela, Wang, Carol A., Yerges-Armstrong, Laura M., Antoniou, Antonis C., Barbieri, Caterina, Coviello, Andrea D., Cucca, Francesco, Demerath, Ellen W., Dunning, Alison M., Gandin, Ilaria, Grove, Megan L., Gudbjartsson, Daniel F., Hocking, Lynne J., Hofman, Albert, Huang, Jinyan, Jackson, Rebecca D., Karasik, David, Kriebel, Jennifer, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Li, Xin, Luan, Jian'an, Maegi, Reedik, Morrison, Alanna C., Padmanabhan, Sandosh, Pirie, Ailith, Polasek, Ozren, Porteous, David, Reiner, Alex P., van der Schouw, Yvonne T., EPIC-InterAct Consortium, and Generation Scotland

Published
2015

30. Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility

Author

Wessel, Jennifer, Chu, Audrey Y., Willems, Sara M., Wang, Shuai, Yaghootkar, Hanieh, Brody, Jennifer A., Dauriz, Marco, Hivert, Marie-France, Raghavan, Sridharan, Lipovich, Leonard, Hidalgo, Bertha, Fox, Keolu, Huffman, Jennifer E., An, Ping, Lu, Yingchang, Rasmussen-Torvik, Laura J., Grarup, Niels, Ehm, Margaret G., Li, Li, Baldridge, Abigail S., Stancakova, Alena, Abrol, Ravinder, Besse, Celine, Boland, Anne, Bork-Jensen, Jette, Fornage, Myriam, Freitag, Daniel F., Garcia, Melissa E., Guo, Xiuqing, Hara, Kazuo, Isaacs, Aaron, Jakobsdottir, Johanna, Lange, Leslie A., Layton, Jill C., Li, Man, Zhao, Jing Hua, Meidtner, Karina, Morrison, Alanna C., Nalls, Mike A., Peters, Marjolein J., Sabater-Lleal, Maria, Schurmann, Claudia, Silveira, Angela, Smith, Albert V., Southam, Lorraine, Stoiber, Marcus H., Strawbridge, Rona J., Taylor, Kent D., Varga, Tibor V., van der Schouw, Yvonne T., The EPIC-InterAct Consortium, Wessel, Jennifer, Chu, Audrey Y., Willems, Sara M., Wang, Shuai, Yaghootkar, Hanieh, Brody, Jennifer A., Dauriz, Marco, Hivert, Marie-France, Raghavan, Sridharan, Lipovich, Leonard, Hidalgo, Bertha, Fox, Keolu, Huffman, Jennifer E., An, Ping, Lu, Yingchang, Rasmussen-Torvik, Laura J., Grarup, Niels, Ehm, Margaret G., Li, Li, Baldridge, Abigail S., Stancakova, Alena, Abrol, Ravinder, Besse, Celine, Boland, Anne, Bork-Jensen, Jette, Fornage, Myriam, Freitag, Daniel F., Garcia, Melissa E., Guo, Xiuqing, Hara, Kazuo, Isaacs, Aaron, Jakobsdottir, Johanna, Lange, Leslie A., Layton, Jill C., Li, Man, Zhao, Jing Hua, Meidtner, Karina, Morrison, Alanna C., Nalls, Mike A., Peters, Marjolein J., Sabater-Lleal, Maria, Schurmann, Claudia, Silveira, Angela, Smith, Albert V., Southam, Lorraine, Stoiber, Marcus H., Strawbridge, Rona J., Taylor, Kent D., Varga, Tibor V., van der Schouw, Yvonne T., and The EPIC-InterAct Consortium

Published
2015

31. Associations between Potentially Modifiable Risk Factors and Alzheimer Disease : A Mendelian Randomization Study

Author

Ostergaard, Soren D., Mukherjee, Shubhabrata, Sharp, Stephen J., Proitsi, Petroula, Lotta, Luca A., Day, Felix, Perry, John R. B., Boehme, Kevin L., Walter, Stefan, Kauwe, John S., Gibbons, Laura E., Larson, Eric B., Powell, John F., Langenberg, Claudia, Crane, Paul K., Wareham, Nicholas J., Scott, Robert A., Alzheimer's Dis Genetics, GERAD1 Consortium, EPIC-InterAct Consortium, van der Schouw, YT, Ostergaard, Soren D., Mukherjee, Shubhabrata, Sharp, Stephen J., Proitsi, Petroula, Lotta, Luca A., Day, Felix, Perry, John R. B., Boehme, Kevin L., Walter, Stefan, Kauwe, John S., Gibbons, Laura E., Larson, Eric B., Powell, John F., Langenberg, Claudia, Crane, Paul K., Wareham, Nicholas J., Scott, Robert A., Alzheimer's Dis Genetics, GERAD1 Consortium, EPIC-InterAct Consortium, and van der Schouw, YT

Published
2015

32. Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility

Author

Wessel, Jennifer, Chu, Audrey Y., Willems, Sara M., Wang, Shuai, Yaghootkar, Hanieh, Brody, Jennifer A., Dauriz, Marco, Hivert, Marie-France, Raghavan, Sridharan, Lipovich, Leonard, Hidalgo, Bertha, Fox, Keolu, Huffman, Jennifer E., An, Ping, Lu, Yingchang, Rasmussen-Torvik, Laura J., Grarup, Niels, Ehm, Margaret G., Li, Li, Baldridge, Abigail S., Stancakova, Alena, Abrol, Ravinder, Besse, Celine, Boland, Anne, Bork-Jensen, Jette, Fornage, Myriam, Freitag, Daniel F., Garcia, Melissa E., Guo, Xiuqing, Hara, Kazuo, Isaacs, Aaron, Jakobsdottir, Johanna, Lange, Leslie A., Layton, Jill C., Li, Man, Zhao, Jing Hua, Meidtner, Karina, Morrison, Alanna C., Nalls, Mike A., Peters, Marjolein J., Sabater-Lleal, Maria, Schurmann, Claudia, Silveira, Angela, Smith, Albert V., Southam, Lorraine, Stoiber, Marcus H., Strawbridge, Rona J., Taylor, Kent D., Varga, Tibor V., van der Schouw, Yvonne T., The EPIC-InterAct Consortium, Wessel, Jennifer, Chu, Audrey Y., Willems, Sara M., Wang, Shuai, Yaghootkar, Hanieh, Brody, Jennifer A., Dauriz, Marco, Hivert, Marie-France, Raghavan, Sridharan, Lipovich, Leonard, Hidalgo, Bertha, Fox, Keolu, Huffman, Jennifer E., An, Ping, Lu, Yingchang, Rasmussen-Torvik, Laura J., Grarup, Niels, Ehm, Margaret G., Li, Li, Baldridge, Abigail S., Stancakova, Alena, Abrol, Ravinder, Besse, Celine, Boland, Anne, Bork-Jensen, Jette, Fornage, Myriam, Freitag, Daniel F., Garcia, Melissa E., Guo, Xiuqing, Hara, Kazuo, Isaacs, Aaron, Jakobsdottir, Johanna, Lange, Leslie A., Layton, Jill C., Li, Man, Zhao, Jing Hua, Meidtner, Karina, Morrison, Alanna C., Nalls, Mike A., Peters, Marjolein J., Sabater-Lleal, Maria, Schurmann, Claudia, Silveira, Angela, Smith, Albert V., Southam, Lorraine, Stoiber, Marcus H., Strawbridge, Rona J., Taylor, Kent D., Varga, Tibor V., van der Schouw, Yvonne T., and The EPIC-InterAct Consortium

Published
2015

33. Rare coding variants and X-linked loci associated with age at menarche

Author

Lunetta, Kathryn L., Day, Felix R., Sulem, Patrick, Ruth, Katherine S., Tung, Joyce Y., Hinds, David A., Esko, Tonu, Elks, Cathy E., Altmaier, Elisabeth, He, Chunyan, Huffman, Jennifer E., Mihailov, Evelin, Porcu, Eleonora, Robino, Antonietta, Rose, Lynda M., Schick, Ursula M., Stolk, Lisette, Teumer, Alexander, Thompson, Deborah J., Traglia, Michela, Wang, Carol A., Yerges-Armstrong, Laura M., Antoniou, Antonis C., Barbieri, Caterina, Coviello, Andrea D., Cucca, Francesco, Demerath, Ellen W., Dunning, Alison M., Gandin, Ilaria, Grove, Megan L., Gudbjartsson, Daniel F., Hocking, Lynne J., Hofman, Albert, Huang, Jinyan, Jackson, Rebecca D., Karasik, David, Kriebel, Jennifer, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Li, Xin, Luan, Jian'an, Maegi, Reedik, Morrison, Alanna C., Padmanabhan, Sandosh, Pirie, Ailith, Polasek, Ozren, Porteous, David, Reiner, Alex P., van der Schouw, Yvonne T., EPIC-InterAct Consortium, Generation Scotland, Lunetta, Kathryn L., Day, Felix R., Sulem, Patrick, Ruth, Katherine S., Tung, Joyce Y., Hinds, David A., Esko, Tonu, Elks, Cathy E., Altmaier, Elisabeth, He, Chunyan, Huffman, Jennifer E., Mihailov, Evelin, Porcu, Eleonora, Robino, Antonietta, Rose, Lynda M., Schick, Ursula M., Stolk, Lisette, Teumer, Alexander, Thompson, Deborah J., Traglia, Michela, Wang, Carol A., Yerges-Armstrong, Laura M., Antoniou, Antonis C., Barbieri, Caterina, Coviello, Andrea D., Cucca, Francesco, Demerath, Ellen W., Dunning, Alison M., Gandin, Ilaria, Grove, Megan L., Gudbjartsson, Daniel F., Hocking, Lynne J., Hofman, Albert, Huang, Jinyan, Jackson, Rebecca D., Karasik, David, Kriebel, Jennifer, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Li, Xin, Luan, Jian'an, Maegi, Reedik, Morrison, Alanna C., Padmanabhan, Sandosh, Pirie, Ailith, Polasek, Ozren, Porteous, David, Reiner, Alex P., van der Schouw, Yvonne T., EPIC-InterAct Consortium, and Generation Scotland

Published
2015

34. Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study.

Author

Østergaard, Søren D, Gandy, Sam1, Østergaard, Søren D, Mukherjee, Shubhabrata, Sharp, Stephen J, Proitsi, Petroula, Lotta, Luca A, Day, Felix, Perry, John RB, Boehme, Kevin L, Walter, Stefan, Kauwe, John S, Gibbons, Laura E, Alzheimer’s Disease Genetics Consortium, GERAD1 Consortium, EPIC-InterAct Consortium, Larson, Eric B, Powell, John F, Langenberg, Claudia, Crane, Paul K, Wareham, Nicholas J, Scott, Robert A, Østergaard, Søren D, Gandy, Sam1, Østergaard, Søren D, Mukherjee, Shubhabrata, Sharp, Stephen J, Proitsi, Petroula, Lotta, Luca A, Day, Felix, Perry, John RB, Boehme, Kevin L, Walter, Stefan, Kauwe, John S, Gibbons, Laura E, Alzheimer’s Disease Genetics Consortium, GERAD1 Consortium, EPIC-InterAct Consortium, Larson, Eric B, Powell, John F, Langenberg, Claudia, Crane, Paul K, Wareham, Nicholas J, and Scott, Robert A

Abstract

BackgroundPotentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD) and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR).Methods and findingsWe used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, NSNPs = 49), fasting glucose (NSNPs = 36), insulin resistance (NSNPs = 10), body mass index (BMI, NSNPs = 32), total cholesterol (NSNPs = 73), HDL-cholesterol (NSNPs = 71), LDL-cholesterol (NSNPs = 57), triglycerides (NSNPs = 39), systolic blood pressure (SBP, NSNPs = 24), smoking initiation (NSNPs = 1), smoking quantity (NSNPs = 3), university completion (NSNPs = 2), and years of education (NSNPs = 1). We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP-AD associations from the International Genomics of Alzheimer's Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62-0.91]; p = 3.4 × 10(-3)). Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10(-8)). Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51-0.89]; p = 6.5 × 10(-3)), although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28). We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1). Pote

Published
2015

35. Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility

Author

Wessel, Jennifer, Chu, Audrey Y., Willems, Sara M., Wang, Shuai, Yaghootkar, Hanieh, Brody, Jennifer A., Dauriz, Marco, Hivert, Marie-France, Raghavan, Sridharan, Lipovich, Leonard, Hidalgo, Bertha, Fox, Keolu, Huffman, Jennifer E., An, Ping, Lu, Yingchang, Rasmussen-Torvik, Laura J., Grarup, Niels, Ehm, Margaret G., Li, Li, Baldridge, Abigail S., Stancakova, Alena, Abrol, Ravinder, Besse, Celine, Boland, Anne, Bork-Jensen, Jette, Fornage, Myriam, Freitag, Daniel F., Garcia, Melissa E., Guo, Xiuqing, Hara, Kazuo, Isaacs, Aaron, Jakobsdottir, Johanna, Lange, Leslie A., Layton, Jill C., Li, Man, Zhao, Jing Hua, Meidtner, Karina, Morrison, Alanna C., Nalls, Mike A., Peters, Marjolein J., Sabater-Lleal, Maria, Schurmann, Claudia, Silveira, Angela, Smith, Albert V., Southam, Lorraine, Stoiber, Marcus H., Strawbridge, Rona J., Taylor, Kent D., Varga, Tibor V., van der Schouw, Yvonne T., The EPIC-InterAct Consortium, Wessel, Jennifer, Chu, Audrey Y., Willems, Sara M., Wang, Shuai, Yaghootkar, Hanieh, Brody, Jennifer A., Dauriz, Marco, Hivert, Marie-France, Raghavan, Sridharan, Lipovich, Leonard, Hidalgo, Bertha, Fox, Keolu, Huffman, Jennifer E., An, Ping, Lu, Yingchang, Rasmussen-Torvik, Laura J., Grarup, Niels, Ehm, Margaret G., Li, Li, Baldridge, Abigail S., Stancakova, Alena, Abrol, Ravinder, Besse, Celine, Boland, Anne, Bork-Jensen, Jette, Fornage, Myriam, Freitag, Daniel F., Garcia, Melissa E., Guo, Xiuqing, Hara, Kazuo, Isaacs, Aaron, Jakobsdottir, Johanna, Lange, Leslie A., Layton, Jill C., Li, Man, Zhao, Jing Hua, Meidtner, Karina, Morrison, Alanna C., Nalls, Mike A., Peters, Marjolein J., Sabater-Lleal, Maria, Schurmann, Claudia, Silveira, Angela, Smith, Albert V., Southam, Lorraine, Stoiber, Marcus H., Strawbridge, Rona J., Taylor, Kent D., Varga, Tibor V., van der Schouw, Yvonne T., and The EPIC-InterAct Consortium

Published
2015

36. Rare coding variants and X-linked loci associated with age at menarche

Author

Lunetta, Kathryn L., Day, Felix R., Sulem, Patrick, Ruth, Katherine S., Tung, Joyce Y., Hinds, David A., Esko, Tonu, Elks, Cathy E., Altmaier, Elisabeth, He, Chunyan, Huffman, Jennifer E., Mihailov, Evelin, Porcu, Eleonora, Robino, Antonietta, Rose, Lynda M., Schick, Ursula M., Stolk, Lisette, Teumer, Alexander, Thompson, Deborah J., Traglia, Michela, Wang, Carol A., Yerges-Armstrong, Laura M., Antoniou, Antonis C., Barbieri, Caterina, Coviello, Andrea D., Cucca, Francesco, Demerath, Ellen W., Dunning, Alison M., Gandin, Ilaria, Grove, Megan L., Gudbjartsson, Daniel F., Hocking, Lynne J., Hofman, Albert, Huang, Jinyan, Jackson, Rebecca D., Karasik, David, Kriebel, Jennifer, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Li, Xin, Luan, Jian'an, Maegi, Reedik, Morrison, Alanna C., Padmanabhan, Sandosh, Pirie, Ailith, Polasek, Ozren, Porteous, David, Reiner, Alex P., van der Schouw, Yvonne T., EPIC-InterAct Consortium, Generation Scotland, Lunetta, Kathryn L., Day, Felix R., Sulem, Patrick, Ruth, Katherine S., Tung, Joyce Y., Hinds, David A., Esko, Tonu, Elks, Cathy E., Altmaier, Elisabeth, He, Chunyan, Huffman, Jennifer E., Mihailov, Evelin, Porcu, Eleonora, Robino, Antonietta, Rose, Lynda M., Schick, Ursula M., Stolk, Lisette, Teumer, Alexander, Thompson, Deborah J., Traglia, Michela, Wang, Carol A., Yerges-Armstrong, Laura M., Antoniou, Antonis C., Barbieri, Caterina, Coviello, Andrea D., Cucca, Francesco, Demerath, Ellen W., Dunning, Alison M., Gandin, Ilaria, Grove, Megan L., Gudbjartsson, Daniel F., Hocking, Lynne J., Hofman, Albert, Huang, Jinyan, Jackson, Rebecca D., Karasik, David, Kriebel, Jennifer, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Li, Xin, Luan, Jian'an, Maegi, Reedik, Morrison, Alanna C., Padmanabhan, Sandosh, Pirie, Ailith, Polasek, Ozren, Porteous, David, Reiner, Alex P., van der Schouw, Yvonne T., EPIC-InterAct Consortium, and Generation Scotland

Published
2015

37. Associations between Potentially Modifiable Risk Factors and Alzheimer Disease : A Mendelian Randomization Study

Author

Ostergaard, Soren D., Mukherjee, Shubhabrata, Sharp, Stephen J., Proitsi, Petroula, Lotta, Luca A., Day, Felix, Perry, John R. B., Boehme, Kevin L., Walter, Stefan, Kauwe, John S., Gibbons, Laura E., Larson, Eric B., Powell, John F., Langenberg, Claudia, Crane, Paul K., Wareham, Nicholas J., Scott, Robert A., Alzheimer's Dis Genetics, GERAD1 Consortium, EPIC-InterAct Consortium, van der Schouw, YT, Ostergaard, Soren D., Mukherjee, Shubhabrata, Sharp, Stephen J., Proitsi, Petroula, Lotta, Luca A., Day, Felix, Perry, John R. B., Boehme, Kevin L., Walter, Stefan, Kauwe, John S., Gibbons, Laura E., Larson, Eric B., Powell, John F., Langenberg, Claudia, Crane, Paul K., Wareham, Nicholas J., Scott, Robert A., Alzheimer's Dis Genetics, GERAD1 Consortium, EPIC-InterAct Consortium, and van der Schouw, YT

Published
2015

38. Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study

Author

JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Circulatory Health, Cardiovasculaire Epidemiologie, Ostergaard, Soren D., Mukherjee, Shubhabrata, Sharp, Stephen J., Proitsi, Petroula, Lotta, Luca A., Day, Felix, Perry, John R. B., Boehme, Kevin L., Walter, Stefan, Kauwe, John S., Gibbons, Laura E., Larson, Eric B., Powell, John F., Langenberg, Claudia, Crane, Paul K., Wareham, Nicholas J., Scott, Robert A., Alzheimer's Dis Genetics, GERAD1 Consortium, EPIC InterAct Consortium, van der Schouw, YT, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Circulatory Health, Cardiovasculaire Epidemiologie, Ostergaard, Soren D., Mukherjee, Shubhabrata, Sharp, Stephen J., Proitsi, Petroula, Lotta, Luca A., Day, Felix, Perry, John R. B., Boehme, Kevin L., Walter, Stefan, Kauwe, John S., Gibbons, Laura E., Larson, Eric B., Powell, John F., Langenberg, Claudia, Crane, Paul K., Wareham, Nicholas J., Scott, Robert A., Alzheimer's Dis Genetics, GERAD1 Consortium, EPIC InterAct Consortium, and van der Schouw, YT

Published
2015

39. Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility

Author

JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Circulatory Health, Cardiovasculaire Epidemiologie, Wessel, Jennifer, Chu, Audrey Y., Willems, Sara M., Wang, Shuai, Yaghootkar, Hanieh, Brody, Jennifer A., Dauriz, Marco, Hivert, Marie-France, Raghavan, Sridharan, Lipovich, Leonard, Hidalgo, Bertha, Fox, Keolu, Huffman, Jennifer E., An, Ping, Lu, Yingchang, Rasmussen-Torvik, Laura J., Grarup, Niels, Ehm, Margaret G., Li, Li, Baldridge, Abigail S., Stancakova, Alena, Abrol, Ravinder, Besse, Celine, Boland, Anne, Bork-Jensen, Jette, Fornage, Myriam, Freitag, Daniel F., Garcia, Melissa E., Guo, Xiuqing, Hara, Kazuo, Isaacs, Aaron, Jakobsdottir, Johanna, Lange, Leslie A., Layton, Jill C., Li, Man, Zhao, Jing Hua, Meidtner, Karina, Morrison, Alanna C., Nalls, Mike A., Peters, Marjolein J., Sabater-Lleal, Maria, Schurmann, Claudia, Silveira, Angela, Smith, Albert V., Southam, Lorraine, Stoiber, Marcus H., Strawbridge, Rona J., Taylor, Kent D., Varga, Tibor V., van der Schouw, Yvonne T., The EPIC-InterAct Consortium, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Circulatory Health, Cardiovasculaire Epidemiologie, Wessel, Jennifer, Chu, Audrey Y., Willems, Sara M., Wang, Shuai, Yaghootkar, Hanieh, Brody, Jennifer A., Dauriz, Marco, Hivert, Marie-France, Raghavan, Sridharan, Lipovich, Leonard, Hidalgo, Bertha, Fox, Keolu, Huffman, Jennifer E., An, Ping, Lu, Yingchang, Rasmussen-Torvik, Laura J., Grarup, Niels, Ehm, Margaret G., Li, Li, Baldridge, Abigail S., Stancakova, Alena, Abrol, Ravinder, Besse, Celine, Boland, Anne, Bork-Jensen, Jette, Fornage, Myriam, Freitag, Daniel F., Garcia, Melissa E., Guo, Xiuqing, Hara, Kazuo, Isaacs, Aaron, Jakobsdottir, Johanna, Lange, Leslie A., Layton, Jill C., Li, Man, Zhao, Jing Hua, Meidtner, Karina, Morrison, Alanna C., Nalls, Mike A., Peters, Marjolein J., Sabater-Lleal, Maria, Schurmann, Claudia, Silveira, Angela, Smith, Albert V., Southam, Lorraine, Stoiber, Marcus H., Strawbridge, Rona J., Taylor, Kent D., Varga, Tibor V., van der Schouw, Yvonne T., and The EPIC-InterAct Consortium

Published
2015

40. Rare coding variants and X-linked loci associated with age at menarche

Author

JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Circulatory Health, Cardiovasculaire Epidemiologie, Lunetta, Kathryn L., Day, Felix R., Sulem, Patrick, Ruth, Katherine S., Tung, Joyce Y., Hinds, David A., Esko, Tonu, Elks, Cathy E., Altmaier, Elisabeth, He, Chunyan, Huffman, Jennifer E., Mihailov, Evelin, Porcu, Eleonora, Robino, Antonietta, Rose, Lynda M., Schick, Ursula M., Stolk, Lisette, Teumer, Alexander, Thompson, Deborah J., Traglia, Michela, Wang, Carol A., Yerges-Armstrong, Laura M., Antoniou, Antonis C., Barbieri, Caterina, Coviello, Andrea D., Cucca, Francesco, Demerath, Ellen W., Dunning, Alison M., Gandin, Ilaria, Grove, Megan L., Gudbjartsson, Daniel F., Hocking, Lynne J., Hofman, Albert, Huang, Jinyan, Jackson, Rebecca D., Karasik, David, Kriebel, Jennifer, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Li, Xin, Luan, Jian'an, Maegi, Reedik, Morrison, Alanna C., Padmanabhan, Sandosh, Pirie, Ailith, Polasek, Ozren, Porteous, David, Reiner, Alex P., van der Schouw, Yvonne T., EPIC InterAct Consortium, Generation Scotland, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Circulatory Health, Cardiovasculaire Epidemiologie, Lunetta, Kathryn L., Day, Felix R., Sulem, Patrick, Ruth, Katherine S., Tung, Joyce Y., Hinds, David A., Esko, Tonu, Elks, Cathy E., Altmaier, Elisabeth, He, Chunyan, Huffman, Jennifer E., Mihailov, Evelin, Porcu, Eleonora, Robino, Antonietta, Rose, Lynda M., Schick, Ursula M., Stolk, Lisette, Teumer, Alexander, Thompson, Deborah J., Traglia, Michela, Wang, Carol A., Yerges-Armstrong, Laura M., Antoniou, Antonis C., Barbieri, Caterina, Coviello, Andrea D., Cucca, Francesco, Demerath, Ellen W., Dunning, Alison M., Gandin, Ilaria, Grove, Megan L., Gudbjartsson, Daniel F., Hocking, Lynne J., Hofman, Albert, Huang, Jinyan, Jackson, Rebecca D., Karasik, David, Kriebel, Jennifer, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Li, Xin, Luan, Jian'an, Maegi, Reedik, Morrison, Alanna C., Padmanabhan, Sandosh, Pirie, Ailith, Polasek, Ozren, Porteous, David, Reiner, Alex P., van der Schouw, Yvonne T., EPIC InterAct Consortium, and Generation Scotland

Published
2015

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