@article {8446, title = {Whole Blood DNA Methylation Signatures of Diet Are Associated With Cardiovascular Disease Risk Factors and All-Cause Mortality.}, journal = {Circ Genom Precis Med}, volume = {13}, year = {2020}, month = {2020 Aug}, pages = {e002766}, abstract = {

BACKGROUND: DNA methylation patterns associated with habitual diet have not been well studied.

METHODS: Diet quality was characterized using a Mediterranean-style diet score and the Alternative Healthy Eating Index score. We conducted ethnicity-specific and trans-ethnic epigenome-wide association analyses for diet quality and leukocyte-derived DNA methylation at over 400 000 CpGs (cytosine-guanine dinucleotides) in 5 population-based cohorts including 6662 European ancestry, 2702 African ancestry, and 360 Hispanic ancestry participants. For diet-associated CpGs identified in epigenome-wide analyses, we conducted Mendelian randomization (MR) analysis to examine their relations to cardiovascular disease risk factors and examined their longitudinal associations with all-cause mortality.

RESULTS: We identified 30 CpGs associated with either Mediterranean-style diet score or Alternative Healthy Eating Index, or both, in European ancestry participants. Among these CpGs, 12 CpGs were significantly associated with all-cause mortality (Bonferroni corrected <1.6{\texttimes}10). Hypermethylation of cg18181703 () was associated with higher scores of both Mediterranean-style diet score and Alternative Healthy Eating Index and lower risk for all-cause mortality (=5.7{\texttimes}10). Ten additional diet-associated CpGs were nominally associated with all-cause mortality (<0.05). MR analysis revealed 8 putatively causal associations for 6 CpGs with 4 cardiovascular disease risk factors (body mass index, triglycerides, high-density lipoprotein cholesterol concentrations, and type 2 diabetes mellitus; Bonferroni corrected MR <4.5{\texttimes}10). For example, hypermethylation of cg11250194 () was associated with lower triglyceride concentrations (MR, =1.5{\texttimes}10).and hypermethylation of cg02079413 (; ) was associated with body mass index (corrected MR, =1{\texttimes}10).

CONCLUSIONS: Habitual diet quality was associated with differential peripheral leukocyte DNA methylation levels of 30 CpGs, most of which were also associated with multiple health outcomes, in European ancestry individuals. These findings demonstrate that integrative genomic analysis of dietary information may reveal molecular targets for disease prevention and treatment.

}, issn = {2574-8300}, doi = {10.1161/CIRCGEN.119.002766}, author = {Ma, Jiantao and Rebholz, Casey M and Braun, Kim V E and Reynolds, Lindsay M and Aslibekyan, Stella and Xia, Rui and Biligowda, Niranjan G and Huan, Tianxiao and Liu, Chunyu and Mendelson, Michael M and Joehanes, Roby and Hu, Emily A and Vitolins, Mara Z and Wood, Alexis C and Lohman, Kurt and Ochoa-Rosales, Carolina and van Meurs, Joyce and Uitterlinden, Andre and Liu, Yongmei and Elhadad, Mohamed A and Heier, Margit and Waldenberger, Melanie and Peters, Annette and Colicino, Elena and Whitsel, Eric A and Baldassari, Antoine and Gharib, Sina A and Sotoodehnia, Nona and Brody, Jennifer A and Sitlani, Colleen M and Tanaka, Toshiko and Hill, W David and Corley, Janie and Deary, Ian J and Zhang, Yan and Sch{\"o}ttker, Ben and Brenner, Hermann and Walker, Maura E and Ye, Shumao and Nguyen, Steve and Pankow, Jim and Demerath, Ellen W and Zheng, Yinan and Hou, Lifang and Liang, Liming and Lichtenstein, Alice H and Hu, Frank B and Fornage, Myriam and Voortman, Trudy and Levy, Daniel} } @article {9456, title = {Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: pooled analysis of 19 cohorts.}, journal = {BMJ}, volume = {380}, year = {2023}, month = {2023 Jan 18}, pages = {e072909}, abstract = {

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.

}, keywords = {alpha-Linolenic Acid, Fatty Acids, Omega-3, Fatty Acids, Unsaturated, Humans, Middle Aged, Prospective Studies, Renal Insufficiency, Chronic, Risk Factors}, issn = {1756-1833}, doi = {10.1136/bmj-2022-072909}, author = {Ong, Kwok Leung and Marklund, Matti and Huang, Liping and Rye, Kerry-Anne and Hui, Nicholas and Pan, Xiong-Fei and Rebholz, Casey M and Kim, Hyunju and Steffen, Lyn M and van Westing, Anniek C and Geleijnse, Johanna M and Hoogeveen, Ellen K and Chen, Yun-Yu and Chien, Kuo-Liong and Fretts, Amanda M and Lemaitre, Rozenn N and Imamura, Fumiaki and Forouhi, Nita G and Wareham, Nicholas J and Birukov, Anna and J{\"a}ger, Susanne and Kuxhaus, Olga and Schulze, Matthias B and de Mello, Vanessa Derenji and Tuomilehto, Jaakko and Uusitupa, Matti and Lindstr{\"o}m, Jaana and Tintle, Nathan and Harris, William S and Yamasaki, Keisuke and Hirakawa, Yoichiro and Ninomiya, Toshiharu and Tanaka, Toshiko and Ferrucci, Luigi and Bandinelli, Stefania and Virtanen, Jyrki K and Voutilainen, Ari and Jayasena, Tharusha and Thalamuthu, Anbupalam and Poljak, Anne and Bustamante, Sonia and Sachdev, Perminder S and Senn, Mackenzie K and Rich, Stephen S and Tsai, Michael Y and Wood, Alexis C and Laakso, Markku and Lankinen, Maria and Yang, Xiaowei and Sun, Liang and Li, Huaixing and Lin, Xu and Nowak, Christoph and Arnl{\"o}v, Johan and Riserus, Ulf and Lind, Lars and Le Goff, M{\'e}lanie and Samieri, Cecilia and Helmer, Catherine and Qian, Frank and Micha, Renata and Tin, Adrienne and K{\"o}ttgen, Anna and de Boer, Ian H and Siscovick, David S and Mozaffarian, Dariush and Wu, Jason HY} } @article {9583, title = {Genome-Wide Interaction Analysis with DASH Diet Score Identified Novel Loci for Systolic Blood Pressure.}, journal = {medRxiv}, year = {2023}, month = {2023 Nov 11}, abstract = {

OBJECTIVE: We examined interactions between genotype and a Dietary Approaches to Stop Hypertension (DASH) diet score in relation to systolic blood pressure (SBP).

METHODS: We analyzed up to 9,420,585 biallelic imputed single nucleotide polymorphisms (SNPs) in up to 127,282 individuals of six population groups (91\% of European population) from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (CHARGE; n=35,660) and UK Biobank (n=91,622) and performed European population-specific and cross-population meta-analyses.

RESULTS: We identified three loci in European-specific analyses and an additional four loci in cross-population analyses at P for interaction < 5e-8. We observed a consistent interaction between rs117878928 at 15q25.1 (minor allele frequency = 0.03) and the DASH diet score (P for interaction = 4e-8; P for heterogeneity = 0.35) in European population, where the interaction effect size was 0.42{\textpm}0.09 mm Hg (P for interaction = 9.4e-7) and 0.20{\textpm}0.06 mm Hg (P for interaction = 0.001) in CHARGE and the UK Biobank, respectively. The 1 Mb region surrounding rs117878928 was enriched with -expression quantitative trait loci (eQTL) variants (P = 4e-273) and -DNA methylation quantitative trait loci (mQTL) variants (P = 1e-300). While the closest gene for rs117878928 is , the highest narrow sense heritability accounted by SNPs potentially interacting with the DASH diet score in this locus was for gene at 15q25.1.

CONCLUSION: We demonstrated gene-DASH diet score interaction effects on SBP in several loci. Studies with larger diverse populations are needed to validate our findings.

}, doi = {10.1101/2023.11.10.23298402}, author = {Guirette, Melanie and Lan, Jessie and McKeown, Nicola and Brown, Michael R and Chen, Han and de Vries, Paul S and Kim, Hyunju and Rebholz, Casey M and Morrison, Alanna C and Bartz, Traci M and Fretts, Amanda M and Guo, Xiuqing and Lemaitre, Rozenn N and Liu, Ching-Ti and Noordam, Raymond and de Mutsert, Ren{\'e}e and Rosendaal, Frits R and Wang, Carol A and Beilin, Lawrence and Mori, Trevor A and Oddy, Wendy H and Pennell, Craig E and Chai, Jin Fang and Whitton, Clare and van Dam, Rob M and Liu, Jianjun and Tai, E Shyong and Sim, Xueling and Neuhouser, Marian L and Kooperberg, Charles and Tinker, Lesley and Franceschini, Nora and Huan, Tianxiao and Winkler, Thomas W and Bentley, Amy R and Gauderman, W James and Heerkens, Luc and Tanaka, Toshiko and van Rooij, Jeroen and Munroe, Patricia B and Warren, Helen R and Voortman, Trudy and Chen, Honglei and Rao, D C and Levy, Daniel and Ma, Jiantao} }