@article {1213, title = {Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies.}, journal = {Lancet}, volume = {375}, year = {2010}, month = {2010 Jun 26}, pages = {2215-22}, abstract = {

BACKGROUND: Uncertainties persist about the magnitude of associations of diabetes mellitus and fasting glucose concentration with risk of coronary heart disease and major stroke subtypes. We aimed to quantify these associations for a wide range of circumstances.

METHODS: We undertook a meta-analysis of individual records of diabetes, fasting blood glucose concentration, and other risk factors in people without initial vascular disease from studies in the Emerging Risk Factors Collaboration. We combined within-study regressions that were adjusted for age, sex, smoking, systolic blood pressure, and body-mass index to calculate hazard ratios (HRs) for vascular disease.

FINDINGS: Analyses included data for 698 782 people (52 765 non-fatal or fatal vascular outcomes; 8.49 million person-years at risk) from 102 prospective studies. Adjusted HRs with diabetes were: 2.00 (95\% CI 1.83-2.19) for coronary heart disease; 2.27 (1.95-2.65) for ischaemic stroke; 1.56 (1.19-2.05) for haemorrhagic stroke; 1.84 (1.59-2.13) for unclassified stroke; and 1.73 (1.51-1.98) for the aggregate of other vascular deaths. HRs did not change appreciably after further adjustment for lipid, inflammatory, or renal markers. HRs for coronary heart disease were higher in women than in men, at 40-59 years than at 70 years and older, and with fatal than with non-fatal disease. At an adult population-wide prevalence of 10\%, diabetes was estimated to account for 11\% (10-12\%) of vascular deaths. Fasting blood glucose concentration was non-linearly related to vascular risk, with no significant associations between 3.90 mmol/L and 5.59 mmol/L. Compared with fasting blood glucose concentrations of 3.90-5.59 mmol/L, HRs for coronary heart disease were: 1.07 (0.97-1.18) for lower than 3.90 mmol/L; 1.11 (1.04-1.18) for 5.60-6.09 mmol/L; and 1.17 (1.08-1.26) for 6.10-6.99 mmol/L. In people without a history of diabetes, information about fasting blood glucose concentration or impaired fasting glucose status did not significantly improve metrics of vascular disease prediction when added to information about several conventional risk factors.

INTERPRETATION: Diabetes confers about a two-fold excess risk for a wide range of vascular diseases, independently from other conventional risk factors. In people without diabetes, fasting blood glucose concentration is modestly and non-linearly associated with risk of vascular disease.

FUNDING: British Heart Foundation, UK Medical Research Council, and Pfizer.

}, keywords = {Adult, Aged, Blood Glucose, Coronary Disease, Diabetes Complications, Diabetes Mellitus, Fasting, Female, Humans, Male, Middle Aged, Risk Factors, Stroke}, issn = {1474-547X}, doi = {10.1016/S0140-6736(10)60484-9}, author = {Sarwar, N and Gao, P and Seshasai, S R Kondapally and Gobin, R and Kaptoge, S and Di Angelantonio, E and Ingelsson, E and Lawlor, D A and Selvin, E and Stampfer, M and Stehouwer, C D A and Lewington, S and Pennells, L and Thompson, A and Sattar, N and White, I R and Ray, K K and Danesh, J} } @article {6606, title = {Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption.}, journal = {Mol Psychiatry}, volume = {20}, year = {2015}, month = {2015 May}, pages = {647-56}, abstract = {

Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91,462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 {\texttimes} 10(-8)).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee.

}, keywords = {Adaptor Proteins, Signal Transducing, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Brain-Derived Neurotrophic Factor, Coffea, Cytochrome P-450 CYP1A2, Food Habits, Genome-Wide Association Study, Humans, Phenotype, Polymorphism, Single Nucleotide}, issn = {1476-5578}, doi = {10.1038/mp.2014.107}, author = {Cornelis, M C and Byrne, E M and Esko, T and Nalls, M A and Ganna, A and Paynter, N and Monda, K L and Amin, N and Fischer, K and Renstrom, F and Ngwa, J S and Huikari, V and Cavadino, A and Nolte, I M and Teumer, A and Yu, K and Marques-Vidal, P and Rawal, R and Manichaikul, A and Wojczynski, M K and Vink, J M and Zhao, J H and Burlutsky, G and Lahti, J and Mikkil{\"a}, V and Lemaitre, R N and Eriksson, J and Musani, S K and Tanaka, T and Geller, F and Luan, J and Hui, J and M{\"a}gi, R and Dimitriou, M and Garcia, M E and Ho, W-K and Wright, M J and Rose, L M and Magnusson, P K E and Pedersen, N L and Couper, D and Oostra, B A and Hofman, A and Ikram, M A and Tiemeier, H W and Uitterlinden, A G and van Rooij, F J A and Barroso, I and Johansson, I and Xue, L and Kaakinen, M and Milani, L and Power, C and Snieder, H and Stolk, R P and Baumeister, S E and Biffar, R and Gu, F and Bastardot, F and Kutalik, Z and Jacobs, D R and Forouhi, N G and Mihailov, E and Lind, L and Lindgren, C and Micha{\"e}lsson, K and Morris, A and Jensen, M and Khaw, K-T and Luben, R N and Wang, J J and M{\"a}nnist{\"o}, S and Per{\"a}l{\"a}, M-M and K{\"a}h{\"o}nen, M and Lehtim{\"a}ki, T and Viikari, J and Mozaffarian, D and Mukamal, K and Psaty, B M and D{\"o}ring, A and Heath, A C and Montgomery, G W and Dahmen, N and Carithers, T and Tucker, K L and Ferrucci, L and Boyd, H A and Melbye, M and Treur, J L and Mellstr{\"o}m, D and Hottenga, J J and Prokopenko, I and T{\"o}njes, A and Deloukas, P and Kanoni, S and Lorentzon, M and Houston, D K and Liu, Y and Danesh, J and Rasheed, A and Mason, M A and Zonderman, A B and Franke, L and Kristal, B S and Karjalainen, J and Reed, D R and Westra, H-J and Evans, M K and Saleheen, D and Harris, T B and Dedoussis, G and Curhan, G and Stumvoll, M and Beilby, J and Pasquale, L R and Feenstra, B and Bandinelli, S and Ordov{\'a}s, J M and Chan, A T and Peters, U and Ohlsson, C and Gieger, C and Martin, N G and Waldenberger, M and Siscovick, D S and Raitakari, O and Eriksson, J G and Mitchell, P and Hunter, D J and Kraft, P and Rimm, E B and Boomsma, D I and Borecki, I B and Loos, R J F and Wareham, N J and Vollenweider, P and Caporaso, N and Grabe, H J and Neuhouser, M L and Wolffenbuttel, B H R and Hu, F B and Hypponen, E and J{\"a}rvelin, M-R and Cupples, L A and Franks, P W and Ridker, P M and van Duijn, C M and Heiss, G and Metspalu, A and North, K E and Ingelsson, E and Nettleton, J A and van Dam, R M and Chasman, D I} } @article {7375, title = {A DNA methylation biomarker of alcohol consumption.}, journal = {Mol Psychiatry}, year = {2016}, month = {2016 Nov 15}, abstract = {

The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54\% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1 {\texttimes} 10(-7). Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P<1 {\texttimes} 10(-7). In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.Molecular Psychiatry advance online publication, 15 November 2016; doi:10.1038/mp.2016.192.

}, issn = {1476-5578}, doi = {10.1038/mp.2016.192}, author = {Liu, C and Marioni, R E and Hedman, {\r A} K and Pfeiffer, L and Tsai, P-C and Reynolds, L M and Just, A C and Duan, Q and Boer, C G and Tanaka, T and Elks, C E and Aslibekyan, S and Brody, J A and K{\"u}hnel, B and Herder, C and Almli, L M and Zhi, D and Wang, Y and Huan, T and Yao, C and Mendelson, M M and Joehanes, R and Liang, L and Love, S-A and Guan, W and Shah, S and McRae, A F and Kretschmer, A and Prokisch, H and Strauch, K and Peters, A and Visscher, P M and Wray, N R and Guo, X and Wiggins, K L and Smith, A K and Binder, E B and Ressler, K J and Irvin, M R and Absher, D M and Hernandez, D and Ferrucci, L and Bandinelli, S and Lohman, K and Ding, J and Trevisi, L and Gustafsson, S and Sandling, J H and Stolk, L and Uitterlinden, A G and Yet, I and Castillo-Fernandez, J E and Spector, T D and Schwartz, J D and Vokonas, P and Lind, L and Li, Y and Fornage, M and Arnett, D K and Wareham, N J and Sotoodehnia, N and Ong, K K and van Meurs, J B J and Conneely, K N and Baccarelli, A A and Deary, I J and Bell, J T and North, K E and Liu, Y and Waldenberger, M and London, S J and Ingelsson, E and Levy, D} }