TY - JOUR T1 - Genome-wide association and functional follow-up reveals new loci for kidney function. JF - PLoS Genet Y1 - 2012 A1 - Pattaro, Cristian A1 - Köttgen, Anna A1 - Teumer, Alexander A1 - Garnaas, Maija A1 - Böger, Carsten A A1 - Fuchsberger, Christian A1 - Olden, Matthias A1 - Chen, Ming-Huei A1 - Tin, Adrienne A1 - Taliun, Daniel A1 - Li, Man A1 - Gao, Xiaoyi A1 - Gorski, Mathias A1 - Yang, Qiong A1 - Hundertmark, Claudia A1 - Foster, Meredith C A1 - O'Seaghdha, Conall M A1 - Glazer, Nicole A1 - Isaacs, Aaron A1 - Liu, Ching-Ti A1 - Smith, Albert V A1 - O'Connell, Jeffrey R A1 - Struchalin, Maksim A1 - Tanaka, Toshiko A1 - Li, Guo A1 - Johnson, Andrew D A1 - Gierman, Hinco J A1 - Feitosa, Mary A1 - Hwang, Shih-Jen A1 - Atkinson, Elizabeth J A1 - Lohman, Kurt A1 - Cornelis, Marilyn C A1 - Johansson, Asa A1 - Tönjes, Anke A1 - Dehghan, Abbas A1 - Chouraki, Vincent A1 - Holliday, Elizabeth G A1 - Sorice, Rossella A1 - Kutalik, Zoltán A1 - Lehtimäki, Terho A1 - Esko, Tõnu A1 - Deshmukh, Harshal A1 - Ulivi, Sheila A1 - Chu, Audrey Y A1 - Murgia, Federico A1 - Trompet, Stella A1 - Imboden, Medea A1 - Kollerits, Barbara A1 - Pistis, Giorgio A1 - Harris, Tamara B A1 - Launer, Lenore J A1 - Aspelund, Thor A1 - Eiriksdottir, Gudny A1 - Mitchell, Braxton D A1 - Boerwinkle, Eric A1 - Schmidt, Helena A1 - Cavalieri, Margherita A1 - Rao, Madhumathi A1 - Hu, Frank B A1 - Demirkan, Ayse A1 - Oostra, Ben A A1 - de Andrade, Mariza A1 - Turner, Stephen T A1 - Ding, Jingzhong A1 - Andrews, Jeanette S A1 - Freedman, Barry I A1 - Koenig, Wolfgang A1 - Illig, Thomas A1 - Döring, Angela A1 - Wichmann, H-Erich A1 - Kolcic, Ivana A1 - Zemunik, Tatijana A1 - Boban, Mladen A1 - Minelli, Cosetta A1 - Wheeler, Heather E A1 - Igl, Wilmar A1 - Zaboli, Ghazal A1 - Wild, Sarah H A1 - Wright, Alan F A1 - Campbell, Harry A1 - Ellinghaus, David A1 - Nöthlings, Ute A1 - Jacobs, Gunnar A1 - Biffar, Reiner A1 - Endlich, Karlhans A1 - Ernst, Florian A1 - Homuth, Georg A1 - Kroemer, Heyo K A1 - Nauck, Matthias A1 - Stracke, Sylvia A1 - Völker, Uwe A1 - Völzke, Henry A1 - Kovacs, Peter A1 - Stumvoll, Michael A1 - Mägi, Reedik A1 - Hofman, Albert A1 - Uitterlinden, André G A1 - Rivadeneira, Fernando A1 - Aulchenko, Yurii S A1 - Polasek, Ozren A1 - Hastie, Nick A1 - Vitart, Veronique A1 - Helmer, Catherine A1 - Wang, Jie Jin A1 - Ruggiero, Daniela A1 - Bergmann, Sven A1 - Kähönen, Mika A1 - Viikari, Jorma A1 - Nikopensius, Tiit A1 - Province, Michael A1 - Ketkar, Shamika A1 - Colhoun, Helen A1 - Doney, Alex A1 - Robino, Antonietta A1 - Giulianini, Franco A1 - Krämer, Bernhard K A1 - Portas, Laura A1 - Ford, Ian A1 - Buckley, Brendan M A1 - Adam, Martin A1 - Thun, Gian-Andri A1 - Paulweber, Bernhard A1 - Haun, Margot A1 - Sala, Cinzia A1 - Metzger, Marie A1 - Mitchell, Paul A1 - Ciullo, Marina A1 - Kim, Stuart K A1 - Vollenweider, Peter A1 - Raitakari, Olli A1 - Metspalu, Andres A1 - Palmer, Colin A1 - Gasparini, Paolo A1 - Pirastu, Mario A1 - Jukema, J Wouter A1 - Probst-Hensch, Nicole M A1 - Kronenberg, Florian A1 - Toniolo, Daniela A1 - Gudnason, Vilmundur A1 - Shuldiner, Alan R A1 - Coresh, Josef A1 - Schmidt, Reinhold A1 - Ferrucci, Luigi A1 - Siscovick, David S A1 - van Duijn, Cornelia M A1 - Borecki, Ingrid A1 - Kardia, Sharon L R A1 - Liu, Yongmei A1 - Curhan, Gary C A1 - Rudan, Igor A1 - Gyllensten, Ulf A1 - Wilson, James F A1 - Franke, Andre A1 - Pramstaller, Peter P A1 - Rettig, Rainer A1 - Prokopenko, Inga A1 - Witteman, Jacqueline C M A1 - Hayward, Caroline A1 - Ridker, Paul A1 - Parsa, Afshin A1 - Bochud, Murielle A1 - Heid, Iris M A1 - Goessling, Wolfram A1 - Chasman, Daniel I A1 - Kao, W H Linda A1 - Fox, Caroline S KW - African Americans KW - Aged KW - Animals KW - Caspase 9 KW - Cyclin-Dependent Kinases KW - DEAD-box RNA Helicases KW - DNA Helicases KW - European Continental Ancestry Group KW - Female KW - Follow-Up Studies KW - Gene Knockdown Techniques KW - Genome-Wide Association Study KW - Glomerular Filtration Rate KW - Humans KW - Kidney KW - Kidney Failure, Chronic KW - Male KW - Middle Aged KW - Phosphoric Diester Hydrolases KW - Zebrafish AB -

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.

VL - 8 IS - 3 U1 - http://www.ncbi.nlm.nih.gov/pubmed/22479191?dopt=Abstract ER - TY - JOUR T1 - Common variants in Mendelian kidney disease genes and their association with renal function. JF - J Am Soc Nephrol Y1 - 2013 A1 - Parsa, Afshin A1 - Fuchsberger, Christian A1 - Köttgen, Anna A1 - O'Seaghdha, Conall M A1 - Pattaro, Cristian A1 - de Andrade, Mariza A1 - Chasman, Daniel I A1 - Teumer, Alexander A1 - Endlich, Karlhans A1 - Olden, Matthias A1 - Chen, Ming-Huei A1 - Tin, Adrienne A1 - Kim, Young J A1 - Taliun, Daniel A1 - Li, Man A1 - Feitosa, Mary A1 - Gorski, Mathias A1 - Yang, Qiong A1 - Hundertmark, Claudia A1 - Foster, Meredith C A1 - Glazer, Nicole A1 - Isaacs, Aaron A1 - Rao, Madhumathi A1 - Smith, Albert V A1 - O'Connell, Jeffrey R A1 - Struchalin, Maksim A1 - Tanaka, Toshiko A1 - Li, Guo A1 - Hwang, Shih-Jen A1 - Atkinson, Elizabeth J A1 - Lohman, Kurt A1 - Cornelis, Marilyn C A1 - Johansson, Asa A1 - Tönjes, Anke A1 - Dehghan, Abbas A1 - Couraki, Vincent A1 - Holliday, Elizabeth G A1 - Sorice, Rossella A1 - Kutalik, Zoltán A1 - Lehtimäki, Terho A1 - Esko, Tõnu A1 - Deshmukh, Harshal A1 - Ulivi, Sheila A1 - Chu, Audrey Y A1 - Murgia, Federico A1 - Trompet, Stella A1 - Imboden, Medea A1 - Kollerits, Barbara A1 - Pistis, Giorgio A1 - Harris, Tamara B A1 - Launer, Lenore J A1 - Aspelund, Thor A1 - Eiriksdottir, Gudny A1 - Mitchell, Braxton D A1 - Boerwinkle, Eric A1 - Schmidt, Helena A1 - Hofer, Edith A1 - Hu, Frank A1 - Demirkan, Ayse A1 - Oostra, Ben A A1 - Turner, Stephen T A1 - Ding, Jingzhong A1 - Andrews, Jeanette S A1 - Freedman, Barry I A1 - Giulianini, Franco A1 - Koenig, Wolfgang A1 - Illig, Thomas A1 - Döring, Angela A1 - Wichmann, H-Erich A1 - Zgaga, Lina A1 - Zemunik, Tatijana A1 - Boban, Mladen A1 - Minelli, Cosetta A1 - Wheeler, Heather E A1 - Igl, Wilmar A1 - Zaboli, Ghazal A1 - Wild, Sarah H A1 - Wright, Alan F A1 - Campbell, Harry A1 - Ellinghaus, David A1 - Nöthlings, Ute A1 - Jacobs, Gunnar A1 - Biffar, Reiner A1 - Ernst, Florian A1 - Homuth, Georg A1 - Kroemer, Heyo K A1 - Nauck, Matthias A1 - Stracke, Sylvia A1 - Völker, Uwe A1 - Völzke, Henry A1 - Kovacs, Peter A1 - Stumvoll, Michael A1 - Mägi, Reedik A1 - Hofman, Albert A1 - Uitterlinden, André G A1 - Rivadeneira, Fernando A1 - Aulchenko, Yurii S A1 - Polasek, Ozren A1 - Hastie, Nick A1 - Vitart, Veronique A1 - Helmer, Catherine A1 - Wang, Jie Jin A1 - Stengel, Bénédicte A1 - Ruggiero, Daniela A1 - Bergmann, Sven A1 - Kähönen, Mika A1 - Viikari, Jorma A1 - Nikopensius, Tiit A1 - Province, Michael A1 - Colhoun, Helen A1 - Doney, Alex A1 - Robino, Antonietta A1 - Krämer, Bernhard K A1 - Portas, Laura A1 - Ford, Ian A1 - Buckley, Brendan M A1 - Adam, Martin A1 - Thun, Gian-Andri A1 - Paulweber, Bernhard A1 - Haun, Margot A1 - Sala, Cinzia A1 - Mitchell, Paul A1 - Ciullo, Marina A1 - Vollenweider, Peter A1 - Raitakari, Olli A1 - Metspalu, Andres A1 - Palmer, Colin A1 - Gasparini, Paolo A1 - Pirastu, Mario A1 - Jukema, J Wouter A1 - Probst-Hensch, Nicole M A1 - Kronenberg, Florian A1 - Toniolo, Daniela A1 - Gudnason, Vilmundur A1 - Shuldiner, Alan R A1 - Coresh, Josef A1 - Schmidt, Reinhold A1 - Ferrucci, Luigi A1 - van Duijn, Cornelia M A1 - Borecki, Ingrid A1 - Kardia, Sharon L R A1 - Liu, Yongmei A1 - Curhan, Gary C A1 - Rudan, Igor A1 - Gyllensten, Ulf A1 - Wilson, James F A1 - Franke, Andre A1 - Pramstaller, Peter P A1 - Rettig, Rainer A1 - Prokopenko, Inga A1 - Witteman, Jacqueline A1 - Hayward, Caroline A1 - Ridker, Paul M A1 - Bochud, Murielle A1 - Heid, Iris M A1 - Siscovick, David S A1 - Fox, Caroline S A1 - Kao, W Linda A1 - Böger, Carsten A KW - Databases, Genetic KW - European Continental Ancestry Group KW - Gene Frequency KW - Genetic Variation KW - Genome-Wide Association Study KW - Humans KW - Kidney KW - Mendelian Randomization Analysis KW - Phenotype KW - Polymorphism, Single Nucleotide KW - Renal Insufficiency, Chronic AB -

Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.

VL - 24 IS - 12 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24029420?dopt=Abstract ER - TY - JOUR T1 - Trends in the incidence of dementia: design and methods in the Alzheimer Cohorts Consortium. JF - Eur J Epidemiol Y1 - 2017 A1 - Chibnik, Lori B A1 - Wolters, Frank J A1 - Bäckman, Kristoffer A1 - Beiser, Alexa A1 - Berr, Claudine A1 - Bis, Joshua C A1 - Boerwinkle, Eric A1 - Bos, Daniel A1 - Brayne, Carol A1 - Dartigues, Jean-François A1 - Darweesh, Sirwan K L A1 - Debette, Stephanie A1 - Davis-Plourde, Kendra L A1 - Dufouil, Carole A1 - Fornage, Myriam A1 - Grasset, Leslie A1 - Gudnason, Vilmundur A1 - Hadjichrysanthou, Christoforos A1 - Helmer, Catherine A1 - Ikram, M Arfan A1 - Ikram, M Kamran A1 - Kern, Silke A1 - Kuller, Lewis H A1 - Launer, Lenore A1 - Lopez, Oscar L A1 - Matthews, Fiona A1 - Meirelles, Osorio A1 - Mosley, Thomas A1 - Ower, Alison A1 - Psaty, Bruce M A1 - Satizabal, Claudia L A1 - Seshadri, Sudha A1 - Skoog, Ingmar A1 - Stephan, Blossom C M A1 - Tzourio, Christophe A1 - Waziry, Reem A1 - Wong, Mei Mei A1 - Zettergren, Anna A1 - Hofman, Albert AB -

Several studies have reported a decline in incidence of dementia which may have large implications for the projected burden of disease, and provide important guidance to preventive efforts. However, reports are conflicting or inconclusive with regard to the impact of gender and education with underlying causes of a presumed declining trend remaining largely unidentified. The Alzheimer Cohorts Consortium aggregates data from nine international population-based cohorts to determine changes in the incidence of dementia since 1990. We will employ Poisson regression models to calculate incidence rates in each cohort and Cox proportional hazard regression to compare 5-year cumulative hazards across study-specific epochs. Finally, we will meta-analyse changes per decade across cohorts, and repeat all analysis stratified by sex, education and APOE genotype. In all cohorts combined, there are data on almost 69,000 people at risk of dementia with the range of follow-up years between 2 and 27. The average age at baseline is similar across cohorts ranging between 72 and 77. Uniting a wide range of disease-specific and methodological expertise in research teams, the first analyses within the Alzheimer Cohorts Consortium are underway to tackle outstanding challenges in the assessment of time-trends in dementia occurrence.

VL - 32 IS - 10 ER - TY - JOUR T1 - Fatty acid biomarkers of dairy fat consumption and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies. JF - PLoS Med Y1 - 2018 A1 - Imamura, Fumiaki A1 - Fretts, Amanda A1 - Marklund, Matti A1 - Ardisson Korat, Andres V A1 - Yang, Wei-Sin A1 - Lankinen, Maria A1 - Qureshi, Waqas A1 - Helmer, Catherine A1 - Chen, Tzu-An A1 - Wong, Kerry A1 - Bassett, Julie K A1 - Murphy, Rachel A1 - Tintle, Nathan A1 - Yu, Chaoyu Ian A1 - Brouwer, Ingeborg A A1 - Chien, Kuo-Liong A1 - Frazier-Wood, Alexis C A1 - Del Gobbo, Liana C A1 - Djoussé, Luc A1 - Geleijnse, Johanna M A1 - Giles, Graham G A1 - de Goede, Janette A1 - Gudnason, Vilmundur A1 - Harris, William S A1 - Hodge, Allison A1 - Hu, Frank A1 - Koulman, Albert A1 - Laakso, Markku A1 - Lind, Lars A1 - Lin, Hung-Ju A1 - McKnight, Barbara A1 - Rajaobelina, Kalina A1 - Riserus, Ulf A1 - Robinson, Jennifer G A1 - Samieri, Cecilia A1 - Siscovick, David S A1 - Soedamah-Muthu, Sabita S A1 - Sotoodehnia, Nona A1 - Sun, Qi A1 - Tsai, Michael Y A1 - Uusitupa, Matti A1 - Wagenknecht, Lynne E A1 - Wareham, Nick J A1 - Wu, Jason HY A1 - Micha, Renata A1 - Forouhi, Nita G A1 - Lemaitre, Rozenn N A1 - Mozaffarian, Dariush KW - Aged KW - Australia KW - Biomarkers KW - Dairy Products KW - Diabetes Mellitus, Type 2 KW - Dietary Fats KW - Europe KW - Fatty Acids KW - Fatty Acids, Monounsaturated KW - Female KW - Humans KW - Incidence KW - Male KW - Middle Aged KW - Prospective Studies KW - Sex Factors KW - Taiwan KW - United States AB -

BACKGROUND: We aimed to investigate prospective associations of circulating or adipose tissue odd-chain fatty acids 15:0 and 17:0 and trans-palmitoleic acid, t16:1n-7, as potential biomarkers of dairy fat intake, with incident type 2 diabetes (T2D).

METHODS AND FINDINGS: Sixteen prospective cohorts from 12 countries (7 from the United States, 7 from Europe, 1 from Australia, 1 from Taiwan) performed new harmonised individual-level analysis for the prospective associations according to a standardised plan. In total, 63,682 participants with a broad range of baseline ages and BMIs and 15,180 incident cases of T2D over the average of 9 years of follow-up were evaluated. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Prespecified interactions by age, sex, BMI, and race/ethnicity were explored in each cohort and were meta-analysed. Potential heterogeneity by cohort-specific characteristics (regions, lipid compartments used for fatty acid assays) was assessed with metaregression. After adjustment for potential confounders, including measures of adiposity (BMI, waist circumference) and lipogenesis (levels of palmitate, triglycerides), higher levels of 15:0, 17:0, and t16:1n-7 were associated with lower incidence of T2D. In the most adjusted model, the hazard ratio (95% CI) for incident T2D per cohort-specific 10th to 90th percentile range of 15:0 was 0.80 (0.73-0.87); of 17:0, 0.65 (0.59-0.72); of t16:1n7, 0.82 (0.70-0.96); and of their sum, 0.71 (0.63-0.79). In exploratory analyses, similar associations for 15:0, 17:0, and the sum of all three fatty acids were present in both genders but stronger in women than in men (pinteraction < 0.001). Whereas studying associations with biomarkers has several advantages, as limitations, the biomarkers do not distinguish between different food sources of dairy fat (e.g., cheese, yogurt, milk), and residual confounding by unmeasured or imprecisely measured confounders may exist.

CONCLUSIONS: In a large meta-analysis that pooled the findings from 16 prospective cohort studies, higher levels of 15:0, 17:0, and t16:1n-7 were associated with a lower risk of T2D.

VL - 15 IS - 10 ER - TY - JOUR T1 - Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality. JF - Circulation Y1 - 2019 A1 - Marklund, Matti A1 - Wu, Jason H Y A1 - Imamura, Fumiaki A1 - Del Gobbo, Liana C A1 - Fretts, Amanda A1 - de Goede, Janette A1 - Shi, Peilin A1 - Tintle, Nathan A1 - Wennberg, Maria A1 - Aslibekyan, Stella A1 - Chen, Tzu-An A1 - de Oliveira Otto, Marcia C A1 - Hirakawa, Yoichiro A1 - Eriksen, Helle Højmark A1 - Kröger, Janine A1 - Laguzzi, Federica A1 - Lankinen, Maria A1 - Murphy, Rachel A A1 - Prem, Kiesha A1 - Samieri, Cecilia A1 - Virtanen, Jyrki A1 - Wood, Alexis C A1 - Wong, Kerry A1 - Yang, Wei-Sin A1 - Zhou, Xia A1 - Baylin, Ana A1 - Boer, Jolanda M A A1 - Brouwer, Ingeborg A A1 - Campos, Hannia A1 - Chaves, Paulo H M A1 - Chien, Kuo-Liong A1 - de Faire, Ulf A1 - Djoussé, Luc A1 - Eiriksdottir, Gudny A1 - El-Abbadi, Naglaa A1 - Forouhi, Nita G A1 - Michael Gaziano, J A1 - Geleijnse, Johanna M A1 - Gigante, Bruna A1 - Giles, Graham A1 - Guallar, Eliseo A1 - Gudnason, Vilmundur A1 - Harris, Tamara A1 - Harris, William S A1 - Helmer, Catherine A1 - Hellenius, Mai-Lis A1 - Hodge, Allison A1 - Hu, Frank B A1 - Jacques, Paul F A1 - Jansson, Jan-Håkan A1 - Kalsbeek, Anya A1 - Khaw, Kay-Tee A1 - Koh, Woon-Puay A1 - Laakso, Markku A1 - Leander, Karin A1 - Lin, Hung-Ju A1 - Lind, Lars A1 - Luben, Robert A1 - Luo, Juhua A1 - McKnight, Barbara A1 - Mursu, Jaakko A1 - Ninomiya, Toshiharu A1 - Overvad, Kim A1 - Psaty, Bruce M A1 - Rimm, Eric A1 - Schulze, Matthias B A1 - Siscovick, David A1 - Skjelbo Nielsen, Michael A1 - Smith, Albert V A1 - Steffen, Brian T A1 - Steffen, Lyn A1 - Sun, Qi A1 - Sundström, Johan A1 - Tsai, Michael Y A1 - Tunstall-Pedoe, Hugh A1 - Uusitupa, Matti I J A1 - van Dam, Rob M A1 - Veenstra, Jenna A1 - Monique Verschuren, W M A1 - Wareham, Nick A1 - Willett, Walter A1 - Woodward, Mark A1 - Yuan, Jian-Min A1 - Micha, Renata A1 - Lemaitre, Rozenn N A1 - Mozaffarian, Dariush A1 - Riserus, Ulf AB -

BACKGROUND: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.

METHODS: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available).

RESULTS: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships.

CONCLUSIONS: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.

VL - 139 IS - 21 ER - TY - JOUR T1 - Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies. JF - Nat Commun Y1 - 2021 A1 - Harris, William S A1 - Tintle, Nathan L A1 - Imamura, Fumiaki A1 - Qian, Frank A1 - Korat, Andres V Ardisson A1 - Marklund, Matti A1 - Djoussé, Luc A1 - Bassett, Julie K A1 - Carmichael, Pierre-Hugues A1 - Chen, Yun-Yu A1 - Hirakawa, Yoichiro A1 - Küpers, Leanne K A1 - Laguzzi, Federica A1 - Lankinen, Maria A1 - Murphy, Rachel A A1 - Samieri, Cecilia A1 - Senn, Mackenzie K A1 - Shi, Peilin A1 - Virtanen, Jyrki K A1 - Brouwer, Ingeborg A A1 - Chien, Kuo-Liong A1 - Eiriksdottir, Gudny A1 - Forouhi, Nita G A1 - Geleijnse, Johanna M A1 - Giles, Graham G A1 - Gudnason, Vilmundur A1 - Helmer, Catherine A1 - Hodge, Allison A1 - Jackson, Rebecca A1 - Khaw, Kay-Tee A1 - Laakso, Markku A1 - Lai, Heidi A1 - Laurin, Danielle A1 - Leander, Karin A1 - Lindsay, Joan A1 - Micha, Renata A1 - Mursu, Jaako A1 - Ninomiya, Toshiharu A1 - Post, Wendy A1 - Psaty, Bruce M A1 - Riserus, Ulf A1 - Robinson, Jennifer G A1 - Shadyab, Aladdin H A1 - Snetselaar, Linda A1 - Sala-Vila, Aleix A1 - Sun, Yangbo A1 - Steffen, Lyn M A1 - Tsai, Michael Y A1 - Wareham, Nicholas J A1 - Wood, Alexis C A1 - Wu, Jason H Y A1 - Hu, Frank A1 - Sun, Qi A1 - Siscovick, David S A1 - Lemaitre, Rozenn N A1 - Mozaffarian, Dariush KW - Aged KW - Aged, 80 and over KW - Cause of Death KW - Fatty Acids, Omega-3 KW - Female KW - Follow-Up Studies KW - Humans KW - Male KW - Middle Aged KW - Mortality, Premature KW - Prospective Studies KW - Protective Factors KW - Risk Factors AB -

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.

VL - 12 IS - 1 ER - TY - JOUR T1 - Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: pooled analysis of 19 cohorts. JF - BMJ Y1 - 2023 A1 - Ong, Kwok Leung A1 - Marklund, Matti A1 - Huang, Liping A1 - Rye, Kerry-Anne A1 - Hui, Nicholas A1 - Pan, Xiong-Fei A1 - Rebholz, Casey M A1 - Kim, Hyunju A1 - Steffen, Lyn M A1 - van Westing, Anniek C A1 - Geleijnse, Johanna M A1 - Hoogeveen, Ellen K A1 - Chen, Yun-Yu A1 - Chien, Kuo-Liong A1 - Fretts, Amanda M A1 - Lemaitre, Rozenn N A1 - Imamura, Fumiaki A1 - Forouhi, Nita G A1 - Wareham, Nicholas J A1 - Birukov, Anna A1 - Jäger, Susanne A1 - Kuxhaus, Olga A1 - Schulze, Matthias B A1 - de Mello, Vanessa Derenji A1 - Tuomilehto, Jaakko A1 - Uusitupa, Matti A1 - Lindström, Jaana A1 - Tintle, Nathan A1 - Harris, William S A1 - Yamasaki, Keisuke A1 - Hirakawa, Yoichiro A1 - Ninomiya, Toshiharu A1 - Tanaka, Toshiko A1 - Ferrucci, Luigi A1 - Bandinelli, Stefania A1 - Virtanen, Jyrki K A1 - Voutilainen, Ari A1 - Jayasena, Tharusha A1 - Thalamuthu, Anbupalam A1 - Poljak, Anne A1 - Bustamante, Sonia A1 - Sachdev, Perminder S A1 - Senn, Mackenzie K A1 - Rich, Stephen S A1 - Tsai, Michael Y A1 - Wood, Alexis C A1 - Laakso, Markku A1 - Lankinen, Maria A1 - Yang, Xiaowei A1 - Sun, Liang A1 - Li, Huaixing A1 - Lin, Xu A1 - Nowak, Christoph A1 - Arnlöv, Johan A1 - Riserus, Ulf A1 - Lind, Lars A1 - Le Goff, Mélanie A1 - Samieri, Cecilia A1 - Helmer, Catherine A1 - Qian, Frank A1 - Micha, Renata A1 - Tin, Adrienne A1 - Köttgen, Anna A1 - de Boer, Ian H A1 - Siscovick, David S A1 - Mozaffarian, Dariush A1 - Wu, Jason HY KW - alpha-Linolenic Acid KW - Fatty Acids, Omega-3 KW - Fatty Acids, Unsaturated KW - Humans KW - Middle Aged KW - Prospective Studies KW - Renal Insufficiency, Chronic KW - Risk Factors AB -

OBJECTIVE: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD).

DESIGN: Pooled analysis.

DATA SOURCES: A consortium of 19 studies from 12 countries identified up to May 2020.

STUDY SELECTION: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate.

DATA EXTRACTION AND SYNTHESIS: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were pooled across cohorts using inverse variance weighted meta-analysis.

MAIN OUTCOME MEASURES: Primary outcome of incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m. In a sensitivity analysis, incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m and <75% of baseline rate.

RESULTS: 25 570 participants were included in the primary outcome analysis and 4944 (19.3%) developed incident CKD during follow-up (weighted median 11.3 years). In multivariable adjusted models, higher levels of total seafood n-3 PUFAs were associated with a lower incident CKD risk (relative risk per interquintile range 0.92, 95% confidence interval 0.86 to 0.98; P=0.009, I=9.9%). In categorical analyses, participants with total seafood n-3 PUFA level in the highest fifth had 13% lower risk of incident CKD compared with those in the lowest fifth (0.87, 0.80 to 0.96; P=0.005, I=0.0%). Plant derived α linolenic acid levels were not associated with incident CKD (1.00, 0.94 to 1.06; P=0.94, I=5.8%). Similar results were obtained in the sensitivity analysis. The association appeared consistent across subgroups by age (≥60 <60 years), estimated glomerular filtration rate (60-89 ≥90 mL/min/1.73 m), hypertension, diabetes, and coronary heart disease at baseline.

CONCLUSIONS: Higher seafood derived n-3 PUFA levels were associated with lower risk of incident CKD, although this association was not found for plant derived n-3 PUFAs. These results support a favourable role for seafood derived n-3 PUFAs in preventing CKD.

VL - 380 ER -