Search

Your search keyword '"Hu, F.B."' showing total 164 results
Start Over Author "Hu, F.B."
164 results on '"Hu, F.B."'

2. Modifiable Risk Factors and Long-term Risk of Type 2 Diabetes Among Individuals With a History of Gestational Diabetes Mellitus: Prospective Cohort Study

Author

Yang, J., primary, Qian, F., additional, Cavarro, J.E., additional, Ley, S.H., additional, Tobais, D.K., additional, Yeung, E., additional, Hinkle, S.N., additional, Bao, W., additional, Li, M., additional, Liu, A., additional, Mills, J.L., additional, Sun, Q., additional, Willett, W.C., additional, Hu, F.B., additional, and Zhang, C., additional

Published
2023
Full Text
View/download PDF

3. Carbohydrate quality, fecal microbiota and cardiometabolic health in older adults: a cohort study.

Author

Atzeni, A., Nishi, S.K., Babio, N., Belzer, C., Konstanti, P., Vioque, J., Corella, D., Castañer, O., Vidal, J., Moreno-Indias, I., Torres-Collado, L., Asensio, E.M., Fitó, M., Gomez-Perez, A.M., Arias, A., Ruiz-Canela, M., Hu, F.B., Tinahones, F.J., Salas-Salvadó, J., Atzeni, A., Nishi, S.K., Babio, N., Belzer, C., Konstanti, P., Vioque, J., Corella, D., Castañer, O., Vidal, J., Moreno-Indias, I., Torres-Collado, L., Asensio, E.M., Fitó, M., Gomez-Perez, A.M., Arias, A., Ruiz-Canela, M., Hu, F.B., Tinahones, F.J., and Salas-Salvadó, J.

Abstract

01 december 2023, Item does not contain fulltext, The impact of carbohydrate quality, measured by the carbohydrate quality index (CQI), on gut microbiota and health has been scarcely investigated. The aim of this study was to cross-sectionally and longitudinally explore the relationships between CQI, fecal microbiota, and cardiometabolic risk factors in an elderly Mediterranean population at high cardiovascular risk. At baseline and 1-year, CQI was assessed from food frequency questionnaires data, cardiometabolic risk factors were measured, and fecal microbiota profiled from 16S sequencing. Multivariable-adjusted linear regression models were fitted to assess the associations between tertiles of baseline CQI, fecal microbiota, and cardiometabolic risk factors at baseline, and between tertiles of 1-year change in CQI, 1-year change in fecal microbiota and cardiometabolic risk factors. Cross-sectionally, higher CQI was positively associated with Shannon alpha diversity index, and abundance of genera Faecalibacterium and Christensenellaceae R7 group, and negatively associated with the abundance of Odoribacter, and uncultured Rhodospirillales genera. Some of these genera were associated with higher glycated hemoglobin and lower body mass index. In addition, we observed a positive association between CQI, and some pathways related with the metabolism of butyrate precursors and plants-origin molecules. Longitudinally, 1-year improvement in CQI was associated with a concurrent increase in the abundance of genera Butyrivibrio. Increased abundance of this genera was associated with 1-year improvement in insulin status. These observations suggest that a better quality of carbohydrate intake is associated with improved metabolic health, and this improvement could be modulated by greater alpha diversity and abundance of specific genera linked to beneficial metabolic outcomes.

Published
2023

4. The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trial

Author

Meir, A.Y., Keller, M., Hoffmann, A., Rinott, E., Tsaban, G., Kaplan, A., Zelicha, H., Hagemann, T., Ceglarek, U., Isermann, B., Shelef, I., Blüher, M., Stumvoll, M., Li, J., Haange, Sven Bastiaan, Engelmann, Beatrice, Rolle-Kampczyk, Ulrike, von Bergen, Martin, Hu, F.B., Stampfer, M.J., Kovacs, P., Liang, L., Shai, I., Meir, A.Y., Keller, M., Hoffmann, A., Rinott, E., Tsaban, G., Kaplan, A., Zelicha, H., Hagemann, T., Ceglarek, U., Isermann, B., Shelef, I., Blüher, M., Stumvoll, M., Li, J., Haange, Sven Bastiaan, Engelmann, Beatrice, Rolle-Kampczyk, Ulrike, von Bergen, Martin, Hu, F.B., Stampfer, M.J., Kovacs, P., Liang, L., and Shai, I.

Abstract

Background Epigenetic age is an estimator of biological age based on DNA methylation; its discrepancy from chronologic age warrants further investigation. We recently reported that greater polyphenol intake benefitted ectopic fats, brain function, and gut microbiota profile, corresponding with elevated urine polyphenols. The effect of polyphenol-rich dietary interventions on biological aging is yet to be determined. Methods We calculated different biological aging epigenetic clocks of different generations (Horvath2013, Hannum2013, Li2018, Horvath skin and blood2018, PhenoAge2018, PCGrimAge2022), their corresponding age and intrinsic age accelerations, and DunedinPACE, all based on DNA methylation (Illumina EPIC array; pre-specified secondary outcome) for 256 participants with abdominal obesity or dyslipidemia, before and after the 18-month DIRECT PLUS randomized controlled trial. Three interventions were assigned: healthy dietary guidelines, a Mediterranean (MED) diet, and a polyphenol-rich, low-red/processed meat Green-MED diet. Both MED groups consumed 28 g walnuts/day (+ 440 mg/day polyphenols). The Green-MED group consumed green tea (3–4 cups/day) and Mankai (Wolffia globosa strain) 500-ml green shake (+ 800 mg/day polyphenols). Adherence to the Green-MED diet was assessed by questionnaire and urine polyphenols metabolomics (high-performance liquid chromatography quadrupole time of flight). Results Baseline chronological age (51.3 ± 10.6 years) was significantly correlated with all methylation age (mAge) clocks with correlations ranging from 0.83 to 0.95; p < 2.2e − 16 for all. While all interventions did not differ in terms of changes between mAge clocks, greater Green-Med diet adherence was associated with a lower 18-month relative change (i.e., greater mAge attenuation) in Li and Hannum mAge (beta = − 0.41, p = 0.004 and beta = − 0.38, p = 0.03, respectively; multivariate models). Greater Li mAge attenuation (multivariate models adjusted for age, se

Published
2023

5. Nut consumption and risk of colorectal cancer in women

Author

Yang, M., Hu, F.B., Giovannucci, E.L., Stampfer, M.J., Willett, W.C., Fuchs, C.S., Wu, K., and Bao, Y.

Subjects
Women -- Health aspects, Nuts -- Health aspects, Colorectal cancer -- Risk factors, Food/cooking/nutrition, Health
Abstract

BACKGROUND/OBJECTIVES: Increasing nut consumption has been associated with reduced risk of obesity and type II diabetes, the risk factors for colorectal cancer. However, the association between nut consumption and colorectal cancer risk is unclear. We aimed to examine the association of long-term nut consumption with risk of colorectal cancer. SUBJECTS/METHODS: We prospectively followed 75 680 women who were free of cancer at baseline in the Nurses' Health Study, and examined the association between nut consumption and colorectal cancer risk. Nut consumption was assessed at baseline and updated every 2-4 years. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. RESULTS: During 2 103 037 person-years of follow-up, we identified 1503 colorectal cancer cases. After adjustment for other known or suspected risk factors, women who consumed nuts 2 or more times per week (that is, ≥ 56 g per week) had a 13% lower risk of colorectal cancer compared with those who rarely consumed nuts, but the association was not statistically significant (RR: 0.87;95% CI: 0.72-1.05;P-trend: 0.06). No association was observed for peanut butter. CONCLUSIONS: In this large prospective cohort of women, frequent nut consumption was not significantly associated with colorectal cancer risk after adjusting for other risk factors. European Journal of Clinical Nutrition (2016) 70, 333-337; doi:10.1038/ejcn.2015.66; published online 6 May 2015, INTRODUCTION Colorectal cancer is the second most common cancer in women and the third most common cancer in men worldwide. (1) Beyond well-known risk factors such as older age, family [...]

Published
2016
Full Text
View/download PDF

6. The effect of high-polyphenol Mediterranean diet on visceral adiposity: the DIRECT PLUS randomized controlled trial

Author

Zelicha, H., Kloting, N., Kaplan, A., Meir, A.Y., Rinott, E., Tsaban, G., Chassidim, Y., Bluher, M., Ceglarek, U., Isermann, B., Stumvoll, M., Quayson, R.N., von Bergen, Martin, Engelmann, Beatrice, Rolle-Kampczyk, Ulrike, Haange, Sven Bastiaan, Tuohy, K.M., Diotallevi, C., Shelef, I., Hu, F.B., Stampfer, M.J., Shai, I., Zelicha, H., Kloting, N., Kaplan, A., Meir, A.Y., Rinott, E., Tsaban, G., Chassidim, Y., Bluher, M., Ceglarek, U., Isermann, B., Stumvoll, M., Quayson, R.N., von Bergen, Martin, Engelmann, Beatrice, Rolle-Kampczyk, Ulrike, Haange, Sven Bastiaan, Tuohy, K.M., Diotallevi, C., Shelef, I., Hu, F.B., Stampfer, M.J., and Shai, I.

Abstract

BackgroundMediterranean (MED) diet is a rich source of polyphenols, which benefit adiposity by several mechanisms. We explored the effect of the green-MED diet, twice fortified in dietary polyphenols and lower in red/processed meat, on visceral adipose tissue (VAT).MethodsIn the 18-month Dietary Intervention Randomized Controlled Trial PoLyphenols UnproceSsed (DIRECT-PLUS) weight-loss trial, 294 participants were randomized to (A) healthy dietary guidelines (HDG), (B) MED, or (C) green-MED diets, all combined with physical activity. Both isocaloric MED groups consumed 28 g/day of walnuts (+ 440 mg/day polyphenols). The green-MED group further consumed green tea (3–4 cups/day) and Wolffia globosa (duckweed strain) plant green shake (100 g frozen cubes/day) (+ 800mg/day polyphenols) and reduced red meat intake. We used magnetic resonance imaging (MRI) to quantify the abdominal adipose tissues.ResultsParticipants (age = 51 years; 88% men; body mass index = 31.2 kg/m2; 29% VAT) had an 89.8% retention rate and 79.3% completed eligible MRIs. While both MED diets reached similar moderate weight (MED: − 2.7%, green-MED: − 3.9%) and waist circumference (MED: − 4.7%, green-MED: − 5.7%) loss, the green-MED dieters doubled the VAT loss (HDG: − 4.2%, MED: − 6.0%, green-MED: − 14.1%; p < 0.05, independent of age, sex, waist circumference, or weight loss). Higher dietary consumption of green tea, walnuts, and Wolffia globosa; lower red meat intake; higher total plasma polyphenols (mainly hippuric acid), and elevated urine urolithin A polyphenol were significantly related to greater VAT loss (p < 0.05, multivariate models).ConclusionsA green-MED diet, enriched with plant-based polyphenols and lower in red/processed meat, may be a potent intervention to promote visceral adiposity regression.

Published
2022

9. Plasma 25-hydroxyvitamin D and risk of metabolic syndrome: an ancillary analysis in the Diabetes Prevention Program

Author

Mitri, J., Nelson, J., Ruthazer, R., Garganta, C., Nathan, D.M., Hu, F.B., Dawson-Hughes, B., and Pittas, A.G.

Subjects
Alfacalcidol -- Health aspects, Diabetes -- Prevention, Health promotion -- Management, Calcifediol -- Health aspects, Vitamin D -- Health aspects, Metabolic diseases -- Risk factors, Company business management, Food/cooking/nutrition, Health
Abstract

BACKGROUND/OBJECTIVES: Low blood levels of 25-hydroxyvitamin D (25OHD) have been associated with cardiometabolic disease but results are inconsistent. The objective of the study was to investigate the association of 25OHD with metabolic syndrome in a population at increased risk for diabetes. SUBJECTS/METHODS: Using baseline data from the placebo and lifestyle intervention arms of the Diabetes Prevention Program (N = 2000), multivariable logistic regression models were used to estimate the odds of prevalent metabolic syndrome and each of its individual components across 25OHD tertiles. Multivariable linear regression was used to estimate the adjusted mean difference of insulin secretion and sensitivity across the same 25OHD tertiles. In participants free of metabolic syndrome at baseline (N = 546), incident metabolic syndrome in the first 2 years of follow-up was assessed using discrete-time proportional hazards regression to test its association with 25OHD concentration. RESULTS: After multivariate adjustment, participants in the highest tertile of 25OHD had lower odds of prevalent metabolic syndrome (odds ratio = 0.62;95% confidence interval (CI) = 0.45-0.84), smaller waist circumference, higher high-density lipoprotein and lower fasting plasma glucose compared with participants in the lowest tertile of 25OHD. Higher plasma 25OHD concentration was associated with greater insulin sensitivity and lower insulin secretion. After multivariate adjustment, there was a nonsignificant lower risk of metabolic syndrome in the highest tertile of 25OHD (hazard ratio = 0.79;95% CI = 0.48-1.32) compared with the lowest tertile. CONCLUSIONS: In a population at increased risk for diabetes, higher plasma 25OHD concentration was inversely associated with prevalent metabolic syndrome and nonsignificantly with incident metabolic syndrome. European Journal of Clinical Nutrition (2014) 68, 376-383; doi:10.1038/ejcn.2013.293; published online 22 January 2014 Keywords: metabolic syndrome; vitamin D; diabetes; Diabetes Prevention Program, INTRODUCTION A growing body of evidence suggests that low 25-hydroxyvitamin D (25OHD) concentration is associated with cardiometabolic disease. (1-3) The apparent link may be explained by vitamin D modifying cardiovascular [...]

Published
2014
Full Text
View/download PDF

10. N-3 fatty acid biomarkers and incident type 2 diabetes: An individual participant-level pooling project of 20 prospective cohort studies.

Author

Qian F., Ardisson Korat A.V., Imamura F., Marklund M., Tintle N., Virtanen J.K., Zhou X., Bassett J.K., Lai H., Hirakawa Y., Chien K.-L., Wood A.C., Lankinen M., Murphy R.A., Samieri C., Pertiwi K., de Mello V.D., Guan W., Forouhi N.G., Wareham N., Consortium I., Hu F.B., Riserus U., Lind L., Harris W.S., Shadyab A.H., Robinson J.G., Steffen L.M., Hodge A., Giles G.G., Ninomiya T., Uusitupa M., Tuomilehto J., Lindstrom J., Laakso M., Siscovick D.S., Helmer C., Geleijnse J.M., Wu J.H.Y., Fretts A., Lemaitre R.N., Micha R., Mozaffarian D., Sun Q., Qian F., Ardisson Korat A.V., Imamura F., Marklund M., Tintle N., Virtanen J.K., Zhou X., Bassett J.K., Lai H., Hirakawa Y., Chien K.-L., Wood A.C., Lankinen M., Murphy R.A., Samieri C., Pertiwi K., de Mello V.D., Guan W., Forouhi N.G., Wareham N., Consortium I., Hu F.B., Riserus U., Lind L., Harris W.S., Shadyab A.H., Robinson J.G., Steffen L.M., Hodge A., Giles G.G., Ninomiya T., Uusitupa M., Tuomilehto J., Lindstrom J., Laakso M., Siscovick D.S., Helmer C., Geleijnse J.M., Wu J.H.Y., Fretts A., Lemaitre R.N., Micha R., Mozaffarian D., and Sun Q.

Abstract

OBJECTIVE Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of a-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis. RESEARCH DESIGN AND METHODS For our analysis we incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed in each cohort following a prespecified protocol, and cohort-specific associations were pooled using inverse variance-weighted meta-analysis. RESULTS A total of 16,693 incident T2D cases were identified during follow-up (median follow-up ranging from 2.5 to 21.2 years). In pooled multivariable analysis, per interquintile range (difference between the 90th and 10th percentiles for each fatty acid), EPA, DPA, DHA, and their sum were associated with lower T2D incidence, with hazard ratios (HRs) and 95% CIs of 0.92 (0.87, 0.96), 0.79 (0.73, 0.85), 0.82 (0.76, 0.89), and 0.81 (0.75, 0.88), respectively (all P < 0.001). ALA was not associated with T2D (HR 0.97 [95% CI 0.92, 1.02]) per interquintile range. Associations were robust across prespecified subgroups as well as in sensitivity analyses. CONCLUSIONS Highercirculating biomarkers of seafood-derivedn-3 fattyacids, including EPA,DPA, DHA, and their sum, were associated with lower risk of T2D in a global consortium of prospective studies. The biomarker of plant-derived ALA was not significantly associated with T2D risk.Copyright © 2021 by the American Diabetes Association.

Published
2021

12. Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus

Author

Van Zuydam, N.R. (Natalie R.), Ladenvall, C. (Claes), Voight, B.F. (Benjamin), Strawbridge, R.J. (Rona), Fernandez-Tajes, J. (Juan), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil R.), Mahajan, A. (Anubha), Vlachopoulou, E. (Efthymia), Goel, A. (Anuj), Kleber, M.E. (Marcus), Nelson, C.P. (Christopher P.), Kwee, L.C. (Lydia Coulter), Esko, T. (Tõnu), Mihailov, E. (Evelin), Mägi, R. (Reedik), Milani, L. (Lili), Fischer, K. (Krista), Kanoni, S. (Stavroula), Kumar, J. (Jitender), Song, C. (Ci), Hartiala, J.A. (Jaana A.), Pedersen, N.L. (Nancy), Perola, M. (Markus), Gieger, C. (Christian), Peters, A. (Annette), Qu, L. (Liming), Willems, S.M. (Sara), Doney, A.S.F. (Alex), Morris, A.D. (Andrew D.), Zheng, Y. (Yan), Sesti, G. (Giorgio), Hu, F.B. (Frank), Qi, L. (Lu), Laakso, M. (Markku), Thorsteinsdottir, U. (Unnur), Grallert, H. (Harald), Duijn, C.M. (Cornelia) van, Reilly, M.P. (Muredach), Ingelsson, E. (Erik), Deloukas, P. (Panos), Kathiresan, S. (Sek), Metspalu, A. (Andres), Shah, S.H. (Svati), Sinisalo, J. (Juha), Salomaa, V. (Veikko), Hamsten, A. (Anders), Samani, N.J. (Nilesh), Ye, S. (Shu), Hazen, S.L. (Stanley), Watkins, H. (Hugh), Saleheen, D. (Danish), Morris, A.P. (Andrew), Colhoun, H.M. (H.), Groop, L. (Leif), McCarthy, M.I. (Mark), Palmer, C.N.A. (Colin), Van Zuydam, N.R. (Natalie R.), Ladenvall, C. (Claes), Voight, B.F. (Benjamin), Strawbridge, R.J. (Rona), Fernandez-Tajes, J. (Juan), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil R.), Mahajan, A. (Anubha), Vlachopoulou, E. (Efthymia), Goel, A. (Anuj), Kleber, M.E. (Marcus), Nelson, C.P. (Christopher P.), Kwee, L.C. (Lydia Coulter), Esko, T. (Tõnu), Mihailov, E. (Evelin), Mägi, R. (Reedik), Milani, L. (Lili), Fischer, K. (Krista), Kanoni, S. (Stavroula), Kumar, J. (Jitender), Song, C. (Ci), Hartiala, J.A. (Jaana A.), Pedersen, N.L. (Nancy), Perola, M. (Markus), Gieger, C. (Christian), Peters, A. (Annette), Qu, L. (Liming), Willems, S.M. (Sara), Doney, A.S.F. (Alex), Morris, A.D. (Andrew D.), Zheng, Y. (Yan), Sesti, G. (Giorgio), Hu, F.B. (Frank), Qi, L. (Lu), Laakso, M. (Markku), Thorsteinsdottir, U. (Unnur), Grallert, H. (Harald), Duijn, C.M. (Cornelia) van, Reilly, M.P. (Muredach), Ingelsson, E. (Erik), Deloukas, P. (Panos), Kathiresan, S. (Sek), Metspalu, A. (Andres), Shah, S.H. (Svati), Sinisalo, J. (Juha), Salomaa, V. (Veikko), Hamsten, A. (Anders), Samani, N.J. (Nilesh), Ye, S. (Shu), Hazen, S.L. (Stanley), Watkins, H. (Hugh), Saleheen, D. (Danish), Morris, A.P. (Andrew), Colhoun, H.M. (H.), Groop, L. (Leif), McCarthy, M.I. (Mark), and Palmer, C.N.A. (Colin)

Abstract

Background: Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (T2D). Methods: To test whether this reflects differential genetic influences on CAD risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66 643 subjects (27 708 with CAD and 24 259 with T2D). Variants showing apparent association with CAD in stratified analyses or evidence of interaction were evaluated in a further 117 787 subjects (16 694 with CAD and 11 537 with T2D). Results: None of the previously characterized CAD loci was found to have specific effects on CAD in T2D individuals, and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background. Conclusions: This study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D.

Published
2020
Full Text
View/download PDF

13. Healthy lifestyle and life expectancy free of cancer, cardiovascular disease, and type 2 diabetes: prospective cohort study

Author

Li, Y. (Yanping), Schoufour, J.D. (Josje), Wang, D.D. (Dong D.), Dhana, K. (Klodian), Pan, A. (Amy), Liu, X. (Xiaoran), Song, M. (Mingyang), Liu, G. (Gang), Shin, H.J. (Hyun Joon), Sun, Q. (Qi), Al-Shaar, L. (Laila), Wang, M. (Molin), Rimm, E.B. (Eric B.), Hertzmark, E. (Ellen), Stampfer, M.J. (Meir), Willett, W.C. (Walter C.), Franco, O.H. (Oscar H.), Hu, F.B. (Frank B.), Li, Y. (Yanping), Schoufour, J.D. (Josje), Wang, D.D. (Dong D.), Dhana, K. (Klodian), Pan, A. (Amy), Liu, X. (Xiaoran), Song, M. (Mingyang), Liu, G. (Gang), Shin, H.J. (Hyun Joon), Sun, Q. (Qi), Al-Shaar, L. (Laila), Wang, M. (Molin), Rimm, E.B. (Eric B.), Hertzmark, E. (Ellen), Stampfer, M.J. (Meir), Willett, W.C. (Walter C.), Franco, O.H. (Oscar H.), and Hu, F.B. (Frank B.)

Abstract

OBJECTIVE: To examine how a healthy lifestyle is related to life expectancy that is free from major chronic diseases. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: The Nurses' Health Study (1980-2014; n=73 196) and the Health Professionals Follow-Up Study (1986-2014; n=38 366). MAIN EXPOSURES: Five low risk lifestyle factors: never smoking, body mass index 18.5-24.9, moderate to vigorous physical activity (≥30 minutes/day), moderate alcohol intake (women: 5-15 g/day; men 5-30 g/day), and a higher diet quality score (upper 40%). MAIN OUTCOME: Life expectancy free of diabetes, cardiovascular diseases, and cancer. RESULTS: The life expectancy free of diabetes, cardiovascular diseases, and cancer at age 50 was 23.7 years (95% confidence interval 22.6 to 24.7) for women who adopted no low risk lifestyle factors, in contrast to 34.4 years (33.1 to 35.5) for women who adopted four or five low risk factors. At age 50, the life expectancy free of any of these chronic diseases was 23.5 (22.3 to 24.7) years among men who adopted no low risk lifestyle factors and 31.1 (29.5 to 32.5) years in men who adopted four or five low risk lifestyle factors. For current male smokers who smoked heavily (≥15 cigarettes/day) or obese men and women (body mass index ≥30), their disease-free life expectancies accounted for the lowest proportion (≤75%) of total life expectancy at age 50. CONCLUSION: Adherence to a healthy lifestyle at mid-life is associated with a longer life expectancy free of major chronic diseases.

Published
2020
Full Text
View/download PDF

18. Olive oil and prevention of chronic diseases: summary of an International conference

Author

Visioli, F. (Francesco), Franco, M. (M.), Toledo, E. (Estefanía), Luchsinger, J. (J.), Willett, W.C. (W. C.), Hu, F.B. (Frank B.), and Martinez-Gonzalez, M.A. (Miguel Ángel)

Subjects
Mediterranean diet, Socioeconomic status, Fatty acids, Neurodegeneration, Cardiovascular disease, Olive oil, Cancer
Abstract

Olive oil is the foremost source of fat in the Mediterranean area and, among other features, sets the Mediterranean diet apart from other dietary regimens. In January 2018, the International Olive Council convened several worldwide experts at the Robert Mondavi Institute (Davis, CA), to discuss and summarize the available data on the effects of olive oil consumption on human health. In this paper, we critically provide a synthesis of the main reported findings, which underscore how and why consuming this oil as part of a balanced diet and healthful lifestyle improves prognosis and extends life- and health-spans.

Published
2018

21. Impact of Healthy Lifestyle Factors on Life Expectancies in the US Population

Author

Li, Y. (Yanping), Pan, A. (An), Wang, D.D. (Dong D.), Liu, X. (Xiaoran), Dhana, K. (Klodian), Franco, O.H. (Oscar), Kaptoge, S. (Stephen), Angelantonio, E. (Emanuele) di, Stampfer, M.J. (Meir J.), Willett, W.C. (Walter C.), Hu, F.B. (Frank B.), Li, Y. (Yanping), Pan, A. (An), Wang, D.D. (Dong D.), Liu, X. (Xiaoran), Dhana, K. (Klodian), Franco, O.H. (Oscar), Kaptoge, S. (Stephen), Angelantonio, E. (Emanuele) di, Stampfer, M.J. (Meir J.), Willett, W.C. (Walter C.), and Hu, F.B. (Frank B.)

Abstract

BACKGROUND: Americans have a shorter life expectancy compared with residents of almost all other high-income countries. We aim to estimate the impact of lifestyle factors on premature mortality and life expectancy in the US population. METHODS: Using data from the Nurses' Health Study (1980-2014; n=78 865) and the Health Professionals Follow-up Study (1986-2014, n=44 354), we defined 5 low-risk lifestyle factors as never smoking, body mass index of 18.5 to 24.9 kg/m2, ≥30 min/d of moderate to vigorous physical activity, moderate alcohol intake, and a high diet quality score (upper 40%), and estimated hazard ratios for the association of total lifestyle score (0-5 scale) with mortality. We used data from the N

Published
2018
Full Text
View/download PDF

23. Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

Author

Hinney, A. (Anke), Kesselmeier, M. (M.), Jall, S. (S.), Volckmar, A.-L. (A. L.), Föcker, M. (M.), Antel, J. (J.), Heid, I.M. (Iris), Winkler, T.W. (Thomas W.), Grant, S.F.A. (S. F.A.), Guo, Y. (Yongli), Bergen, A.W. (Andrew), Grant, S.F.A. (Struan), Berrettini, W. (Wade), Hakonarson, H. (Hakon), Herpertz-Dahlmann, B. (B.), De Zwaan, M. (M.), Herzog, W. (W.), Ehrlich, S.M. (Stefan), Zipfel, S. (S.), Egberts, K. (Karin), Adan, R. (R.), Brandys, M. (M.), Elburg, A.A. (Annemarie) van, Boraska Perica, V. (V.), Müller, T.D., Tschöp, M.H. (M. H.), Zeggini, E. (Eleftheria), Bulik, C.M. (C. M.), Collier, D.A. (David), Scherag, A. (A.), Hebebrand, J. (J.), Tschop, M. (Matthias), Floyd, J. (Jamie), Thornton, L.M. (Laura), Huckins, L.M. (Laura M), Southam, L. (Lorraine), Rayner, N.W. (Nigel William), Tachmazidou, I. (Ioanna), Klump, K.L. (K. L.), Treasure, J. (Janet), Lewis, C.M. (Cathryn), Schmidt, U. (Ulrike), Tozzi, F. (Federica), Iezebrink, K. (Kirsty), Gorwood, P. (Philip), Kas, M.J.H. (Martien), Favaro, A. (Angela), Santonastaso, P. (Paolo), Fernández-Aranda, F. (Fernando), Gratacos, M. (Monica), Rybakowski, F. (Filip), Dmitrzak-Weglarz, M. (Monika), Kaprio, J. (Jaakko), Keski-Rahkonen, A. (Anna), Raevuori-Helkamaa, A. (Anu), Furth, E.F. (Eric) van, Slof-Op’t Landt, M.C.T. (Margarita C. T.), Hudson, J.I. (James I), Knudsen, G.P.S. (Gun Peggy S.), Monteleone, P. (Palmiero), Kaplan, A.S. (Allan S), Karwautz, A. (Andreas), Li, D. (Dong), Komaki, G. (Gen), Ando, T. (Tetsuya), Inoko, H. (Hidetoshi), Esko, T. (T.), Fischer, K. (Krista), Männik, K. (Katrin), Metspalu, A. (Andres), Baker, J.H. (Jessica H), Cone, R.D. (Roger D), Esko, T. (Tõnu), DeSocio, J.E. (Janiece E), Hilliard, C.E. (Christopher E), O’Toole, J.K. (Julie K), Pantel, J. (Jacques), Szatkiewicz, J.P. (Jin P), Taico, C. (Chrysecolla), Zerwas, S. (Stephanie), Trace, S.E. (Sara E), Davis, O.S.P. (Oliver S.), Helder, S. (Sietske), Bühren, K. (Katharina), Burghardt, R. (Roland), Imgart, H. (Hartmut), Scherag, A. (Andre), Boni, C. (Claudette), Ramoz, N. (Nicolas), Versini, A. (Audrey), Danner, U.N. (Unna N), de Kove, C. (Carolien), Hendriks, J. (Judith), Koeleman, B.P.C. (Bobby P. C.), Ophoff, R.A. (Roel), Strengman, E. (Eric), Bruson, A. (Alice), Clementi, M. (Maurizio), Degortes, D. (Daniela), Forzan, M. (Monica), Tenconi, E. (Elena), Docampo, E. (Elisa), Jiménez-Murcia, G.E.S. (Geòrgia Escaramí Susana), Lissowska, J. (Jolanta), Rajewski, A. (Andrzej), Szeszenia-Dabrowska, N. (Neonila), Slopien, A. (Agnieszka), Hauser, J. (J.), Karhunen, L. (Leila), Meulenbelt, I. (Ingrid), Slagboom, P.E. (Eline), Tortorella, A. (Alfonso), Maj, M. (Mario), Dedoussis, G.V. (George), Dedoussis, G.V. (G. V.), Koeleman, B.P.C. (Bobby), Gonidakis, F. (Fragiskos), Tziouvas, K. (Konstantinos), Tsitsika, A. (Artemis), Papezova, H. (Hana), Slachtova, L. (Lenka), Martaskova, D. (Debora), Kennedy, J.L., Levitan, R.D. (Robert D), Yilmaz, Z. (Zeynep), Huemer, J. (Julia), Koubek, D. (Doris), Merl, E. (Elisabeth), Wagner, G. (Gudrun), Lichtenstein, P. (Paul), Breen, G. (Gerome), Cohen-Woods, S. (Sarah), Farmer, A.E. (Anne E), Mcguffin, P. (Peter), Cichon, S. (Sven), Giegling, I. (Ina), Herms, S. (Stefan), Rujescu, D. (Dan), Schreiber, S. (Stefan), Wichmann, H.E. (Heinz Erich), Sladek, R. (Rob), Gambaro, G. (Giovanni), Soranzo, N. (Nicole), Julia, A. (Antonio), Marsal, S. (Sara), Rabionet, R. (Raquel), Gaborieau, V. (Valerie), Dick, D.M. (Danielle), Palotie, A. (A.), Ripatti, S. (Samuli), Widen, E., Espeseth, T. (Thomas), Lundervold, A.J. (Astri), Reinvang, I. (Ivar), Steen, V.M. (Vidar), Le Hellard, S. (Stephanie), Mattingsdal, M. (Morten), Ntalla, I. (Ioanna), Bencko, V. (Vladimir), Foretova, L. (Lenka), Janout, V. (Vladimir), Navratilova, M. (Marie), Pinto, D. (Dalila), Scherer, S.W. (Stephen W), Carlberg, L. (Laura), Schosser, A. (Alexandra), Alfredsson, L. (Lars), Pinto, D. (Duane), Scherer, S.W. (Stephen), Padyukov, L. (Leonid), Finan, C. (Chris), Kalsi, G. (Gursharan), Roberts, M. (Marion), Logan, D.W. (Darren W), Peltonen, L. (Leena Johanna), Ritchie, G.R.S. (Graham R.S.), Barrett, J.C. (Jeffrey), Estivill, X. (Xavier), Sullivan, P.F. (Patrick), Anderson, C.A. (Carl A), McGinnis, R. (Ralph), Sambrook, J. (Jennifer), Stephens, J. (Jonathan), Ouwehand, W.H. (Willem), McArdle, P.F. (P. F.), Ring, S.M. (Susan), Strachan, D.P. (David), Alexander, G. (Graeme), Conlon, P.J. (Peter J), Dominiczak, A. (Anna), Duncanson, A. (Audrey), Padyukov, L. (L.), Langford, C. (Cordelia), Lord, G. (Graham), Conlon, P. (Peter), Sandford, R. (Richard), Sheerin, N. (Neil), Vannberg, F.O. (Frederik O), Blackburn, H. (Hannah), Maxwell, A.P. (A.), Edkins, T. (Ted), Gillman, M.W. (Matthew W.), Gray, E. (Emma), Hunt, S.E. (Sarah E), Nengut, S.-G. (Suna-Gumuscu), Potter, S.C. (Simon), Rich, S.S. (Stephen), Simpkin, D. (Douglas), Whittaker, P. (Pamela), Ang, W.Q. (Wei), Atalay, M. (Mustafa), Beijsterveldt, C.E.M. (Toos) van, Bergen, N. (N.), Benke, K. (K.), Berry, D. (Diane), Boomsma, D.I. (Dorret), Bradfield, J.P. (Jonathan), Charoen, P. (Pimphen), Coin, L. (Lachlan), Cooper, C. (C.), Cousminer, D.L. (Diana), Das, S. (Shikta), Elliott, P. (P.), Evans, D.M. (D. M.), Feenstra, B. (B.), Flexeder, C. (Claudia), Frayling, T.M. (Timothy), Freathy, R.M. (Rachel), Gaillard, R. (R.), Geller, F. (Frank), Groen-Blokhuis, M. (Maria), Goh, L.K. (L. K.), Guxens Junyent, M. (Mònica), Hattersley, A.T. (Andrew), Haworth, C.M.A. (Claire M.), Hadley, D. (D.), Heinrich, J. (J.), Hirschhorn, J.N. (Joel), Hocher, B. (Berthold), Holloway, J.W. (J. W.), Holst, J.J., Hottenga, J.J. (Jouke Jan), Horikoshi, M. (Momoko), Huikari, V. (Ville), Hypponen, E. (E.), Iñiguez, C. (C.), Jaddoe, V.W. (V. W.), Jarvelin, M.R. (M. R.), Kaakinen, M. (M.), Kilpeläinen, T.O. (Tuomas), Hypponen, E. (Elina), Kowgier, M. (Matthew), Lakka, T.A. (Timo), Cooper, C. (Charles), Lange, L.A. (Leslie), Lawlor, D.A. (D. A.), Lehtimäki, T. (Terho), Lewin, A. (Alex), Elliott, P. (Paul), Lindi, V. (Virpi), Maggi, R. (Reedik), Feenstra, B. (Bjarke), McCarthy, M.I. (M. I.), Melbye, M. (Mads), Middeldorp, C.M. (Christel), Millwood, I.Y. (Iona), Mohlke, K.L. (Karen), Mook-Kanamori, D.O. (D. O.), Murray, J.C. (Jeffrey), Nivard, M. (Michel), Nohr, C. (Christian), Oken, E. (Emily), Ong, K.K. (K. K.), O'Reilly, P.F. (P. F.), Palmer, C. (Cameron), Panoutsopoulou, K. (K.), Pararajasingham, J. (Jennifer), Pearson, E.R. (E. R.), Pennell, C.E. (Craig), Power, C. (Christopher), Price, T.S. (Thomas), Prokopenko, I. (Inga), Raitakari, O.T. (O. T.), Rodriguez, A. (A.), Salem, R.M. (Rany), Saw, S.M. (S. M.), Sebert, S. (S.), Siitonen, N. (Niina), Jaddoe, V.W.V. (Vincent), Sørensen, T.I.A. (Thorkild), Sovio, U. (Ulla), Lawlor, D.A. (Debbie), Sunyer, J. (J.), Taal, H.R. (Rob), Teo, Y.Y. (Y. Y.), Thiering, E. (Elisabeth), Tiesler, C. (C.), Timpson, N.J. (Nicholas), Uitterlinden, A.G. (André), Valcárcel, B. (Beatriz), Teo, Y.Y. (Yik Ying), White, S.J. (Stefan), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (J. F.), Yaghootkar, H. (H.), Elks, C.E. (Cathy), Perry, J.R. (J. R.), Sulem, P. (Patrick), Chasman, D.I. (Daniel), Franceschini, N. (Nora), He, C. (C.), Lunetta, K.L. (Kathryn), Visser, J.A. (Jenny), Byrne, E.M. (E. M.), Gudbjartsson, D.F. (Daniel), Koller, D.L. (Daniel), Kutalik, Z. (Zoltán), Lin, P. (P.), Mangino, M. (Massimo), Byrne, E.M. (Enda), Smith, A.V. (Albert), Stolk, L. (Lisette), Wingerden, S. (Sophie) van, Zhao, J.H. (J. H.), Albrecht, E. (Eva), Corre, T. (Tanguy), Ingelsson, E. (Erik), Hayward, C. (Caroline), Magnusson, P.K. (Patrik), Smith, A.V. (Davey), Chanock, S.J. (Stephen), Warrington, M. (M.), Zgaga, L. (L.), Alavere, H. (Helene), Amin, N. (Najaf), Aspelund, T. (T.), Ulivi, S. (Shelia), Sunyer, J. (Jordi), Berenson, G. (Gerald), Bergmann, S.M. (Sven), Boerwinkle, E. (E.), Buring, J.E. (Julie), Busonero, F. (F.), Barroso, I.E. (Inês), Chanock, S.J. (S. J.), Warrington, N.M. (Nicole), Couper, D.J. (David), Coviello, A.D. (Andrea), Busonero, F., Faire, U. (Ulf) de, de Geus, E.J. (E. J.), Deloukas, P. (Panagiotis), Döring, A. (Angela), Davey Smith, G. (G.), Adamo, P. (Pio) d', Eiriksdottir, G. (Gudny), Geus, E.J.C. (Eco) de, Hagen, K. (Knut), Ferrucci, L. (L.), Folsom, A.R. (A. R.), Foroud, T. (T.), Garcia, M.E. (M.), Gasparini, P. (P.), Gieger, C. (Christian), Gudnason, V. (V.), Folsom, A.R. (Aaron), Hankinson, S.E. (S. E.), Ferreli, L. (Liana), Gasparini, P. (Paolo), Hernandez, D.G. (Dena), Hofman, A. (Albert), Hu, F.B. (F. B.), Illig, T. (T.), Jarvelin, M.-R. (Marjo-Riitta), Johnson, A.D. (Andrew), Karasik, D. (David), Khaw, K.T. (K. T.), Kiel, D.P. (Douglas P.), Kolcic, I. (Ivana), Kraft, P. (Peter), Launer, L.J. (Lenore), Laven, J.S. (J. S.), Li, S. (S.), Liu, J. (J.), Levy, D. (D.), Martin, N.G. (N. G.), Aspelund, T. (Thor), Nalls, M.A. (Michael), Navarro, P. (Pau), Nelis, M. (M.), Ness, A.R. (A. R.), Boerwinkle, E.A. (Eric), Oostra, B.A. (Ben), Peacock, M. (M.), Pare, G. (Guillame), Parker, A.N. (Alex), Pedersen, N.L. (Nancy), Cornelis, M. (Marilyn), Polasek, O. (Ozren), Plump, A.S. (A. S.), Peacock, M. (Munro), Porcu, E. (Eleonora), Rafnar, T. (Thorunn), Rice, J.P. (John), Rivadeneira, F. (F.), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D. (D.), Scuteri, A. (A.), Segrè, A.V. (Ayellet), Foroud, T. (Tatiana), Srinivasan, S.R. (Sathanur), Tammesoo, M.L. (M. L.), Tikkanen, E. (Emmi), Toniolo, D. (Daniela), Scuteri, A. (Angelo), Tryggvadottir, L. (Laufey), Tyrer, J. (J.), Uda, M. (M.), van Dam, R.M. (R. M.), Meurs, J.B.J. (Joyce) van, Vollenweider, P. (Peter), Waeber, G. (Gérard), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Weedon, M.N. (Michael), Wright, A.F. (Alan), Young, L. (L.), Zhai, G. (G.), Zhuang, W.V. (W. V.), Bierut, L.J. (L. J.), Boyd, H.A. (H. A.), Crisponi, L. (Laura), Demerath, E.W. (E. W.), Duijn, C.M. (Cornelia) van, Econs, M.J. (M. J.), Harris, T.B. (Tamara), Bierut, L.J. (Laura), Loos, R.J.F. (Ruth), Ridker, P.M. (Paul), Demerath, E.W. (Ellen), Streeten, E.A. (Elizabeth), Econs, M.J. (Michael), Thorsteinsdottir, U. (Unnur), Widen, E. (E.), Murabito, J. (Joanne), Ness, A.R. (Andrew), Spector, T.D. (Timothy), Crawford, S. (Steve), Crow, S. (Scott), Fichter, M.M. (M. M.), Halmi, K.A. (K. A.), Palotie, A. (Aarno), La Via, M. (Maria), Mitchell, J. (James), Strober, M. (Michael), Rotondo, A. (Alessandro), Woodside, D.B. (D Blake), Keel, P. (Pamela), Lilenfeld, L. (Lisa), Rivadeneira Ramirez, F. (Fernando), Magistretti, P. (Pierre), Montgomery, G.W. (G. W.), Hinney, A. (Anke), Kesselmeier, M. (M.), Jall, S. (S.), Volckmar, A.-L. (A. L.), Föcker, M. (M.), Antel, J. (J.), Heid, I.M. (Iris), Winkler, T.W. (Thomas W.), Grant, S.F.A. (S. F.A.), Guo, Y. (Yongli), Bergen, A.W. (Andrew), Grant, S.F.A. (Struan), Berrettini, W. (Wade), Hakonarson, H. (Hakon), Herpertz-Dahlmann, B. (B.), De Zwaan, M. (M.), Herzog, W. (W.), Ehrlich, S.M. (Stefan), Zipfel, S. (S.), Egberts, K. (Karin), Adan, R. (R.), Brandys, M. (M.), Elburg, A.A. (Annemarie) van, Boraska Perica, V. (V.), Müller, T.D., Tschöp, M.H. (M. H.), Zeggini, E. (Eleftheria), Bulik, C.M. (C. M.), Collier, D.A. (David), Scherag, A. (A.), Hebebrand, J. (J.), Tschop, M. (Matthias), Floyd, J. (Jamie), Thornton, L.M. (Laura), Huckins, L.M. (Laura M), Southam, L. (Lorraine), Rayner, N.W. (Nigel William), Tachmazidou, I. (Ioanna), Klump, K.L. (K. L.), Treasure, J. (Janet), Lewis, C.M. (Cathryn), Schmidt, U. (Ulrike), Tozzi, F. (Federica), Iezebrink, K. (Kirsty), Gorwood, P. (Philip), Kas, M.J.H. (Martien), Favaro, A. (Angela), Santonastaso, P. (Paolo), Fernández-Aranda, F. (Fernando), Gratacos, M. (Monica), Rybakowski, F. (Filip), Dmitrzak-Weglarz, M. (Monika), Kaprio, J. (Jaakko), Keski-Rahkonen, A. (Anna), Raevuori-Helkamaa, A. (Anu), Furth, E.F. (Eric) van, Slof-Op’t Landt, M.C.T. (Margarita C. T.), Hudson, J.I. (James I), Knudsen, G.P.S. (Gun Peggy S.), Monteleone, P. (Palmiero), Kaplan, A.S. (Allan S), Karwautz, A. (Andreas), Li, D. (Dong), Komaki, G. (Gen), Ando, T. (Tetsuya), Inoko, H. (Hidetoshi), Esko, T. (T.), Fischer, K. (Krista), Männik, K. (Katrin), Metspalu, A. (Andres), Baker, J.H. (Jessica H), Cone, R.D. (Roger D), Esko, T. (Tõnu), DeSocio, J.E. (Janiece E), Hilliard, C.E. (Christopher E), O’Toole, J.K. (Julie K), Pantel, J. (Jacques), Szatkiewicz, J.P. (Jin P), Taico, C. (Chrysecolla), Zerwas, S. (Stephanie), Trace, S.E. (Sara E), Davis, O.S.P. (Oliver S.), Helder, S. (Sietske), Bühren, K. (Katharina), Burghardt, R. (Roland), Imgart, H. (Hartmut), Scherag, A. (Andre), Boni, C. (Claudette), Ramoz, N. (Nicolas), Versini, A. (Audrey), Danner, U.N. (Unna N), de Kove, C. (Carolien), Hendriks, J. (Judith), Koeleman, B.P.C. (Bobby P. C.), Ophoff, R.A. (Roel), Strengman, E. (Eric), Bruson, A. (Alice), Clementi, M. (Maurizio), Degortes, D. (Daniela), Forzan, M. (Monica), Tenconi, E. (Elena), Docampo, E. (Elisa), Jiménez-Murcia, G.E.S. (Geòrgia Escaramí Susana), Lissowska, J. (Jolanta), Rajewski, A. (Andrzej), Szeszenia-Dabrowska, N. (Neonila), Slopien, A. (Agnieszka), Hauser, J. (J.), Karhunen, L. (Leila), Meulenbelt, I. (Ingrid), Slagboom, P.E. (Eline), Tortorella, A. (Alfonso), Maj, M. (Mario), Dedoussis, G.V. (George), Dedoussis, G.V. (G. V.), Koeleman, B.P.C. (Bobby), Gonidakis, F. (Fragiskos), Tziouvas, K. (Konstantinos), Tsitsika, A. (Artemis), Papezova, H. (Hana), Slachtova, L. (Lenka), Martaskova, D. (Debora), Kennedy, J.L., Levitan, R.D. (Robert D), Yilmaz, Z. (Zeynep), Huemer, J. (Julia), Koubek, D. (Doris), Merl, E. (Elisabeth), Wagner, G. (Gudrun), Lichtenstein, P. (Paul), Breen, G. (Gerome), Cohen-Woods, S. (Sarah), Farmer, A.E. (Anne E), Mcguffin, P. (Peter), Cichon, S. (Sven), Giegling, I. (Ina), Herms, S. (Stefan), Rujescu, D. (Dan), Schreiber, S. (Stefan), Wichmann, H.E. (Heinz Erich), Sladek, R. (Rob), Gambaro, G. (Giovanni), Soranzo, N. (Nicole), Julia, A. (Antonio), Marsal, S. (Sara), Rabionet, R. (Raquel), Gaborieau, V. (Valerie), Dick, D.M. (Danielle), Palotie, A. (A.), Ripatti, S. (Samuli), Widen, E., Espeseth, T. (Thomas), Lundervold, A.J. (Astri), Reinvang, I. (Ivar), Steen, V.M. (Vidar), Le Hellard, S. (Stephanie), Mattingsdal, M. (Morten), Ntalla, I. (Ioanna), Bencko, V. (Vladimir), Foretova, L. (Lenka), Janout, V. (Vladimir), Navratilova, M. (Marie), Pinto, D. (Dalila), Scherer, S.W. (Stephen W), Carlberg, L. (Laura), Schosser, A. (Alexandra), Alfredsson, L. (Lars), Pinto, D. (Duane), Scherer, S.W. (Stephen), Padyukov, L. (Leonid), Finan, C. (Chris), Kalsi, G. (Gursharan), Roberts, M. (Marion), Logan, D.W. (Darren W), Peltonen, L. (Leena Johanna), Ritchie, G.R.S. (Graham R.S.), Barrett, J.C. (Jeffrey), Estivill, X. (Xavier), Sullivan, P.F. (Patrick), Anderson, C.A. (Carl A), McGinnis, R. (Ralph), Sambrook, J. (Jennifer), Stephens, J. (Jonathan), Ouwehand, W.H. (Willem), McArdle, P.F. (P. F.), Ring, S.M. (Susan), Strachan, D.P. (David), Alexander, G. (Graeme), Conlon, P.J. (Peter J), Dominiczak, A. (Anna), Duncanson, A. (Audrey), Padyukov, L. (L.), Langford, C. (Cordelia), Lord, G. (Graham), Conlon, P. (Peter), Sandford, R. (Richard), Sheerin, N. (Neil), Vannberg, F.O. (Frederik O), Blackburn, H. (Hannah), Maxwell, A.P. (A.), Edkins, T. (Ted), Gillman, M.W. (Matthew W.), Gray, E. (Emma), Hunt, S.E. (Sarah E), Nengut, S.-G. (Suna-Gumuscu), Potter, S.C. (Simon), Rich, S.S. (Stephen), Simpkin, D. (Douglas), Whittaker, P. (Pamela), Ang, W.Q. (Wei), Atalay, M. (Mustafa), Beijsterveldt, C.E.M. (Toos) van, Bergen, N. (N.), Benke, K. (K.), Berry, D. (Diane), Boomsma, D.I. (Dorret), Bradfield, J.P. (Jonathan), Charoen, P. (Pimphen), Coin, L. (Lachlan), Cooper, C. (C.), Cousminer, D.L. (Diana), Das, S. (Shikta), Elliott, P. (P.), Evans, D.M. (D. M.), Feenstra, B. (B.), Flexeder, C. (Claudia), Frayling, T.M. (Timothy), Freathy, R.M. (Rachel), Gaillard, R. (R.), Geller, F. (Frank), Groen-Blokhuis, M. (Maria), Goh, L.K. (L. K.), Guxens Junyent, M. (Mònica), Hattersley, A.T. (Andrew), Haworth, C.M.A. (Claire M.), Hadley, D. (D.), Heinrich, J. (J.), Hirschhorn, J.N. (Joel), Hocher, B. (Berthold), Holloway, J.W. (J. W.), Holst, J.J., Hottenga, J.J. (Jouke Jan), Horikoshi, M. (Momoko), Huikari, V. (Ville), Hypponen, E. (E.), Iñiguez, C. (C.), Jaddoe, V.W. (V. W.), Jarvelin, M.R. (M. R.), Kaakinen, M. (M.), Kilpeläinen, T.O. (Tuomas), Hypponen, E. (Elina), Kowgier, M. (Matthew), Lakka, T.A. (Timo), Cooper, C. (Charles), Lange, L.A. (Leslie), Lawlor, D.A. (D. A.), Lehtimäki, T. (Terho), Lewin, A. (Alex), Elliott, P. (Paul), Lindi, V. (Virpi), Maggi, R. (Reedik), Feenstra, B. (Bjarke), McCarthy, M.I. (M. I.), Melbye, M. (Mads), Middeldorp, C.M. (Christel), Millwood, I.Y. (Iona), Mohlke, K.L. (Karen), Mook-Kanamori, D.O. (D. O.), Murray, J.C. (Jeffrey), Nivard, M. (Michel), Nohr, C. (Christian), Oken, E. (Emily), Ong, K.K. (K. K.), O'Reilly, P.F. (P. F.), Palmer, C. (Cameron), Panoutsopoulou, K. (K.), Pararajasingham, J. (Jennifer), Pearson, E.R. (E. R.), Pennell, C.E. (Craig), Power, C. (Christopher), Price, T.S. (Thomas), Prokopenko, I. (Inga), Raitakari, O.T. (O. T.), Rodriguez, A. (A.), Salem, R.M. (Rany), Saw, S.M. (S. M.), Sebert, S. (S.), Siitonen, N. (Niina), Jaddoe, V.W.V. (Vincent), Sørensen, T.I.A. (Thorkild), Sovio, U. (Ulla), Lawlor, D.A. (Debbie), Sunyer, J. (J.), Taal, H.R. (Rob), Teo, Y.Y. (Y. Y.), Thiering, E. (Elisabeth), Tiesler, C. (C.), Timpson, N.J. (Nicholas), Uitterlinden, A.G. (André), Valcárcel, B. (Beatriz), Teo, Y.Y. (Yik Ying), White, S.J. (Stefan), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (J. F.), Yaghootkar, H. (H.), Elks, C.E. (Cathy), Perry, J.R. (J. R.), Sulem, P. (Patrick), Chasman, D.I. (Daniel), Franceschini, N. (Nora), He, C. (C.), Lunetta, K.L. (Kathryn), Visser, J.A. (Jenny), Byrne, E.M. (E. M.), Gudbjartsson, D.F. (Daniel), Koller, D.L. (Daniel), Kutalik, Z. (Zoltán), Lin, P. (P.), Mangino, M. (Massimo), Byrne, E.M. (Enda), Smith, A.V. (Albert), Stolk, L. (Lisette), Wingerden, S. (Sophie) van, Zhao, J.H. (J. H.), Albrecht, E. (Eva), Corre, T. (Tanguy), Ingelsson, E. (Erik), Hayward, C. (Caroline), Magnusson, P.K. (Patrik), Smith, A.V. (Davey), Chanock, S.J. (Stephen), Warrington, M. (M.), Zgaga, L. (L.), Alavere, H. (Helene), Amin, N. (Najaf), Aspelund, T. (T.), Ulivi, S. (Shelia), Sunyer, J. (Jordi), Berenson, G. (Gerald), Bergmann, S.M. (Sven), Boerwinkle, E. (E.), Buring, J.E. (Julie), Busonero, F. (F.), Barroso, I.E. (Inês), Chanock, S.J. (S. J.), Warrington, N.M. (Nicole), Couper, D.J. (David), Coviello, A.D. (Andrea), Busonero, F., Faire, U. (Ulf) de, de Geus, E.J. (E. J.), Deloukas, P. (Panagiotis), Döring, A. (Angela), Davey Smith, G. (G.), Adamo, P. (Pio) d', Eiriksdottir, G. (Gudny), Geus, E.J.C. (Eco) de, Hagen, K. (Knut), Ferrucci, L. (L.), Folsom, A.R. (A. R.), Foroud, T. (T.), Garcia, M.E. (M.), Gasparini, P. (P.), Gieger, C. (Christian), Gudnason, V. (V.), Folsom, A.R. (Aaron), Hankinson, S.E. (S. E.), Ferreli, L. (Liana), Gasparini, P. (Paolo), Hernandez, D.G. (Dena), Hofman, A. (Albert), Hu, F.B. (F. B.), Illig, T. (T.), Jarvelin, M.-R. (Marjo-Riitta), Johnson, A.D. (Andrew), Karasik, D. (David), Khaw, K.T. (K. T.), Kiel, D.P. (Douglas P.), Kolcic, I. (Ivana), Kraft, P. (Peter), Launer, L.J. (Lenore), Laven, J.S. (J. S.), Li, S. (S.), Liu, J. (J.), Levy, D. (D.), Martin, N.G. (N. G.), Aspelund, T. (Thor), Nalls, M.A. (Michael), Navarro, P. (Pau), Nelis, M. (M.), Ness, A.R. (A. R.), Boerwinkle, E.A. (Eric), Oostra, B.A. (Ben), Peacock, M. (M.), Pare, G. (Guillame), Parker, A.N. (Alex), Pedersen, N.L. (Nancy), Cornelis, M. (Marilyn), Polasek, O. (Ozren), Plump, A.S. (A. S.), Peacock, M. (Munro), Porcu, E. (Eleonora), Rafnar, T. (Thorunn), Rice, J.P. (John), Rivadeneira, F. (F.), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D. (D.), Scuteri, A. (A.), Segrè, A.V. (Ayellet), Foroud, T. (Tatiana), Srinivasan, S.R. (Sathanur), Tammesoo, M.L. (M. L.), Tikkanen, E. (Emmi), Toniolo, D. (Daniela), Scuteri, A. (Angelo), Tryggvadottir, L. (Laufey), Tyrer, J. (J.), Uda, M. (M.), van Dam, R.M. (R. M.), Meurs, J.B.J. (Joyce) van, Vollenweider, P. (Peter), Waeber, G. (Gérard), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Weedon, M.N. (Michael), Wright, A.F. (Alan), Young, L. (L.), Zhai, G. (G.), Zhuang, W.V. (W. V.), Bierut, L.J. (L. J.), Boyd, H.A. (H. A.), Crisponi, L. (Laura), Demerath, E.W. (E. W.), Duijn, C.M. (Cornelia) van, Econs, M.J. (M. J.), Harris, T.B. (Tamara), Bierut, L.J. (Laura), Loos, R.J.F. (Ruth), Ridker, P.M. (Paul), Demerath, E.W. (Ellen), Streeten, E.A. (Elizabeth), Econs, M.J. (Michael), Thorsteinsdottir, U. (Unnur), Widen, E. (E.), Murabito, J. (Joanne), Ness, A.R. (Andrew), Spector, T.D. (Timothy), Crawford, S. (Steve), Crow, S. (Scott), Fichter, M.M. (M. M.), Halmi, K.A. (K. A.), Palotie, A. (Aarno), La Via, M. (Maria), Mitchell, J. (James), Strober, M. (Michael), Rotondo, A. (Alessandro), Woodside, D.B. (D Blake), Keel, P. (Pamela), Lilenfeld, L. (Lisa), Rivadeneira Ramirez, F. (Fernando), Magistretti, P. (Pierre), and Montgomery, G.W. (G. W.)

Abstract

The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10-5, Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10-06/Pfemales: 3.45 × 10-07/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the associa

Published
2017
Full Text
View/download PDF

24. 1000 Genomes-based metaanalysis identifies 10 novel loci for kidney function

Author

Gorski, M. (Mathias), Most, P.J. (Peter) van der, Teumer, A. (Alexander), Chu, A.Y. (Audrey Y), Li, M. (Man), Mijatovic, V. (Vladan), Nolte, I.M. (Ilja), Cocca, M. (Massimiliano), Taliun, D. (Daniel), Gomez, F. (Felicia), Li, Y. (Yong), Tayo, B. (Bamidele), Tin, A. (Adrienne), Feitosa, M.F., Aspelund, T. (Thor), Attia, J. (John), Biffar, R. (Reiner), Bochud, M. (Murielle), Boerwinkle, E. (Eric), Borecki, I.B. (Ingrid), Bottinger, E.P. (Erwin), Chen, M.-H. (Ming-Huei), Chouraki, V. (Vincent), Ciullo, M. (Marina), Coresh, J. (Josef), Cornelis, M. (Marilyn), Curhan, G.C. (Gary), D'Adamo, A.P. (Adamo Pio), Dehghan, A. (Abbas), Dengler, L. (Laura), Ding, J. (Jingzhong), Eiriksdottir, G. (Gudny), Endlich, K. (Karlhans), Enroth, S. (Stefan), Esko, T. (Tõnu), Franco, O.H. (Oscar H.), Gasparini, P. (Paolo), Gieger, C. (Christian), Girotto, S., Gottesman, O. (Omri), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hancock, S.J. (Stephen J.), Harris, T.B. (Tamara), Helmer, C. (Catherine), Höllerer, S. (Simon), Hofer, E. (Edith), Hofman, A. (Albert), Holliday, E.G. (Elizabeth), Homuth, G. (Georg), Hu, F.B. (Frank), Huth, C. (Cornelia), Hutri-Kähönen, N. (Nina), Hwang, S.-J. (Shih-Jen), Imboden, M. (Medea), Johansson, A. (Åsa), Kähönen, M. (Mika), König, W. (Wolfgang), Kramer, H. (Holly), Krämer, B.K. (Bernhard), Kumar, A. (Ashish), Kutalik, Z. (Zoltán), Lambert, J.-C. (J.), Launer, L.J. (Lenore), Lehtimäki, T. (Terho), De Borst, M.H. (Martin H.), Navis, G. (Gerjan), Swertz, M. (Morris), Liu, Y. (YongMei), Lohman, K. (Kurt), Loos, R.J.F. (Ruth), Lu, Y. (Yingchang), Lyytikäinen, L.-P. (Leo-Pekka), McEvoy, M. (Mark), Meisinger, C. (Christa), Meitinger, T. (Thomas), Metspalu, A. (Andres), Metzger, M. (Marie), Mihailov, E. (Evelin), Mitchell, P. (Paul), Nauck, M. (Matthias), Oldehinkel, A.J. (Albertine), Olden, M. (Matthias), Penninx, B.W.J.H. (Brenda), Pistis, G. (Giorgio), Pramstaller, P.P. (Peter P.), Probst-Hensch, N.M. (Nicole M.), Raitakari, O.T. (Olli T.), Rettig, R. (Rainer), Ridker, P.M. (Paul), Rivadeneira, F. (Fernando), Robino, A. (Antonietta), Rosas, S.E. (Sylvia E.), Ruderfer, D. (Douglas), Ruggiero, D., Saba, Y. (Yasaman), Sala, C. (Cinzia), Schmidt, H. (Helena), Schmidt, R. (Reinhold), Scott, R.J. (Rodney J.), Sedaghat, S. (Sanaz), Smith, A.V. (Albert), Sorice, R., Stengel, B. (Bernd), Stracke, S. (Sylvia), Strauch, K. (Konstantin), Toniolo, D. (Daniela), Uitterlinden, A.G. (André), Ulivi, S. (Sheila), Viikari, J. (Jorma), Völker, U. (Uwe), Vollenweider, P. (Peter), Völzke, H. (Henry), Vuckovic, D. (Dragana), Waldenberger, M. (Melanie), Wang, J.J. (Jie Jin), Yang, Q. (Qiong Fang), Chasman, D.I. (Daniel), Tromp, G. (Gerard), Snieder, H. (Harold), Heid, I.M. (Iris), Fox, C.S. (Caroline), Köttgen, A. (Anna), Penninx, B.W.J.H., Böger, C.A. (Carsten), Fuchsberger, C. (Christian), Gorski, M. (Mathias), Most, P.J. (Peter) van der, Teumer, A. (Alexander), Chu, A.Y. (Audrey Y), Li, M. (Man), Mijatovic, V. (Vladan), Nolte, I.M. (Ilja), Cocca, M. (Massimiliano), Taliun, D. (Daniel), Gomez, F. (Felicia), Li, Y. (Yong), Tayo, B. (Bamidele), Tin, A. (Adrienne), Feitosa, M.F., Aspelund, T. (Thor), Attia, J. (John), Biffar, R. (Reiner), Bochud, M. (Murielle), Boerwinkle, E. (Eric), Borecki, I.B. (Ingrid), Bottinger, E.P. (Erwin), Chen, M.-H. (Ming-Huei), Chouraki, V. (Vincent), Ciullo, M. (Marina), Coresh, J. (Josef), Cornelis, M. (Marilyn), Curhan, G.C. (Gary), D'Adamo, A.P. (Adamo Pio), Dehghan, A. (Abbas), Dengler, L. (Laura), Ding, J. (Jingzhong), Eiriksdottir, G. (Gudny), Endlich, K. (Karlhans), Enroth, S. (Stefan), Esko, T. (Tõnu), Franco, O.H. (Oscar H.), Gasparini, P. (Paolo), Gieger, C. (Christian), Girotto, S., Gottesman, O. (Omri), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hancock, S.J. (Stephen J.), Harris, T.B. (Tamara), Helmer, C. (Catherine), Höllerer, S. (Simon), Hofer, E. (Edith), Hofman, A. (Albert), Holliday, E.G. (Elizabeth), Homuth, G. (Georg), Hu, F.B. (Frank), Huth, C. (Cornelia), Hutri-Kähönen, N. (Nina), Hwang, S.-J. (Shih-Jen), Imboden, M. (Medea), Johansson, A. (Åsa), Kähönen, M. (Mika), König, W. (Wolfgang), Kramer, H. (Holly), Krämer, B.K. (Bernhard), Kumar, A. (Ashish), Kutalik, Z. (Zoltán), Lambert, J.-C. (J.), Launer, L.J. (Lenore), Lehtimäki, T. (Terho), De Borst, M.H. (Martin H.), Navis, G. (Gerjan), Swertz, M. (Morris), Liu, Y. (YongMei), Lohman, K. (Kurt), Loos, R.J.F. (Ruth), Lu, Y. (Yingchang), Lyytikäinen, L.-P. (Leo-Pekka), McEvoy, M. (Mark), Meisinger, C. (Christa), Meitinger, T. (Thomas), Metspalu, A. (Andres), Metzger, M. (Marie), Mihailov, E. (Evelin), Mitchell, P. (Paul), Nauck, M. (Matthias), Oldehinkel, A.J. (Albertine), Olden, M. (Matthias), Penninx, B.W.J.H. (Brenda), Pistis, G. (Giorgio), Pramstaller, P.P. (Peter P.), Probst-Hensch, N.M. (Nicole M.), Raitakari, O.T. (Olli T.), Rettig, R. (Rainer), Ridker, P.M. (Paul), Rivadeneira, F. (Fernando), Robino, A. (Antonietta), Rosas, S.E. (Sylvia E.), Ruderfer, D. (Douglas), Ruggiero, D., Saba, Y. (Yasaman), Sala, C. (Cinzia), Schmidt, H. (Helena), Schmidt, R. (Reinhold), Scott, R.J. (Rodney J.), Sedaghat, S. (Sanaz), Smith, A.V. (Albert), Sorice, R., Stengel, B. (Bernd), Stracke, S. (Sylvia), Strauch, K. (Konstantin), Toniolo, D. (Daniela), Uitterlinden, A.G. (André), Ulivi, S. (Sheila), Viikari, J. (Jorma), Völker, U. (Uwe), Vollenweider, P. (Peter), Völzke, H. (Henry), Vuckovic, D. (Dragana), Waldenberger, M. (Melanie), Wang, J.J. (Jie Jin), Yang, Q. (Qiong Fang), Chasman, D.I. (Daniel), Tromp, G. (Gerard), Snieder, H. (Harold), Heid, I.M. (Iris), Fox, C.S. (Caroline), Köttgen, A. (Anna), Penninx, B.W.J.H., Böger, C.A. (Carsten), and Fuchsberger, C. (Christian)

Abstract

HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-Analysis of kidney function based on the estimated glomerular filtration rate (EGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10-8 previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, whi

Published
2017
Full Text
View/download PDF

25. Diet-dependent acid load and type 2 diabetes: pooled results from three prospective cohort studie

Author

Kiefte-de Jong, J.C. (Jessica), Li, Y. (Yanping), Chen, M. (Mu), Curhan, G.C. (Gary), Mattei, J. (Josiemer), Malik, V.S. (Vasanti S.), Forman, J.P. (John P.), Franco, O.H. (Oscar), Hu, F.B. (Frank), Kiefte-de Jong, J.C. (Jessica), Li, Y. (Yanping), Chen, M. (Mu), Curhan, G.C. (Gary), Mattei, J. (Josiemer), Malik, V.S. (Vasanti S.), Forman, J.P. (John P.), Franco, O.H. (Oscar), and Hu, F.B. (Frank)

Abstract

Aims/hypothesis: Studies suggest a potential link between low-grade metabolic acidosis and type 2 diabetes. A western dietary pattern increases daily acid load but the association between diet-dependent acid load and type 2 diabetes is still unclear. This study aimed to assess whether diet-dependent acid load is associated with the risk of type 2 diabetes. Methods: We examined the association between energy-adjusted net endogenous acid production (NEAP), potential renal acid load (PRAL) and animal protein-to-potassium ratio (A:P) on incident type 2 diabetes in 67,433 women from the Nurses’ Health Study, 84,310 women from the Nurses’ Health Study II and 35,743 men from the Health Professionals’ Follow-up Study who were free from type 2 diabetes, cardiovascular disease and cancer at baseline. Study-specific HRs were estimated using Cox proportional hazards models with time-varying covariates and were pooled using a random effects meta-analysis. Results: We documented 15,305 cases of type 2 diabetes during 4,025,131 person-years of follow-up. After adjustment for diabetes risk factors, dietary NEAP, PRAL and A:P were positively associated with type 2 diabetes (pooled HR [95% CI] for highest (Q5) vs lowest quintile (Q1): 1.29 [1.22, 1.37], ptrend <0.0001; 1.29 [1.22, 1.36], ptrend <0.0001 and 1.32 [1.24, 1.40], ptrend <0.0001 for NEAP, PRAL and A:P, respectively). These results were not fully explained by other dietary factors including glycaemic load and dietary quality (HR [95% CI] for Q5 vs Q1: 1.21 [1.09, 1.33], ptrend <0.0001; 1.19 [1.08, 1.30] and 1.26 [1.17, 1.36], ptrend <0.0001 for NEAP, PRAL and A:P, respectively). Conclusions/interpretation: This study suggests that higher diet-dependent acid load is associated with an increased risk of type 2 diabetes. This association is not fully explained by diabetes risk factors and overall diet quality.

Published
2017
Full Text
View/download PDF

26. Epigenome-wide association study (EWAS) on lipids: the Rotterdam Study

Author

Braun, K.V.E. (Kim), Dhana, K. (Klodian), Vries, P.S. (Paul) de, Voortman, R.G. (Trudy), Meurs, J.B.J. (Joyce) van, Uitterlinden, A.G. (André), Hofman, A. (Albert), Hu, F.B. (Frank B.), Franco, O.H. (Oscar), Dehghan, A. (Abbas), Braun, K.V.E. (Kim), Dhana, K. (Klodian), Vries, P.S. (Paul) de, Voortman, R.G. (Trudy), Meurs, J.B.J. (Joyce) van, Uitterlinden, A.G. (André), Hofman, A. (Albert), Hu, F.B. (Frank B.), Franco, O.H. (Oscar), and Dehghan, A. (Abbas)

Abstract

Background: DNA methylation is a key epigenetic mechanism that is suggested to be associated with blood lipid levels. We aimed to identify CpG sites at which DNA methylation levels are associated with blood levels of triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol in 725 participants of the Rotterdam Study, a population-based cohort study. Subsequently, we sought replication in a non-overlapping set of 760 participants. Results: Genome-wide methylation levels were measured in whole blood using the Illumina Methylation 450 array. Associations between lipid levels and DNA methylation beta values were examined using linear mixed-effect models. All models were adjusted for sex, age, smoking, white blood cell proportions, array number, and position on array. A Bonferroni-corrected p value lower than 1.08 × 10−7 was considered statistically significant. Five CpG sites annotated to genes including DHCR24, CPT1A, ABCG1, and SREBF1 were identified and replicated. Four CpG sites were associated with triglycerides, including CpG sites annotated to CPT1A (cg00574958 and cg17058475), ABCG1 (cg06500161), and SREBF1 (cg11024682). Two CpG sites were associated with HDL-C, including ABCG1 (cg06500161) and DHCR24 (cg17901584). No significant associations were observed with LDL-C or total cholesterol. Conclusions: We report an association of HDL-C levels with methylation of a CpG site near DHCR24, a protein-coding gene involved in cholesterol biosynthesis, which has previously been reported to be associated with other metabolic traits. Furthermore, we confirmed previously reported associations of methylation of CpG sites within CPT1A, ABCG1, and SREBF1 and lipids. These results provide insight in the mechanisms that are involved in lipid metabolism.

Published
2017
Full Text
View/download PDF

27. Corrigendum: 1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function.

Author

Gorski, M., Most, PJV, Teumer, A., Chu, A.Y., Li, M., Mijatovic, V., Nolte, I.M., Cocca, M., Taliun, D., Gomez, F., Li, Y., Tayo, B., Tin, A., Feitosa, M.F., Aspelund, T., Attia, J., Biffar, R., Bochud, M., Boerwinkle, E., Borecki, I., Bottinger, E.P., Chen, M.H., Chouraki, V., Ciullo, M., Coresh, J., Cornelis, M.C., Curhan, G.C., Adamo, A.P., Dehghan, A., Dengler, L., Ding, J., Eiriksdottir, G., Endlich, K., Enroth, S., Esko, T., Franco, O.H., Gasparini, P., Gieger, C., Girotto, G., Gottesman, O., Gudnason, V., Gyllensten, U., Hancock, S.J., Harris, T.B., Helmer, C., Höllerer, S., Hofer, E., Hofman, A., Holliday, E.G., Homuth, G., Hu, F.B., Huth, C., Hutri-Kähönen, N., Hwang, S.J., Imboden, M., Johansson, Å., Kähönen, M., König, W., Kramer, H., Krämer, B.K., Kumar, A., Kutalik, Z., Lambert, J.C., Launer, L.J., Lehtimäki, T., de Borst, M.H., Navis, G., Swertz, M., Liu, Y., Lohman, K., Loos, RJF, Lu, Y., Lyytikäinen, L.P., McEvoy, M.A., Meisinger, C., Meitinger, T., Metspalu, A., Metzger, M., Mihailov, E., Mitchell, P., Nauck, M., Oldehinkel, A.J., Olden, M., Wjh Penninx, B., Pistis, G., Pramstaller, P.P., Probst-Hensch, N., Raitakari, O.T., Rettig, R., Ridker, P.M., Rivadeneira, F., Robino, A., Rosas, S.E., Ruderfer, D., Ruggiero, D., Saba, Y., Sala, C., Schmidt, H., Schmidt, R., Scott, R.J., Sedaghat, S., Smith, A.V., Sorice, R., Stengel, B., Stracke, S., Strauch, K., Toniolo, D., Uitterlinden, A.G., Ulivi, S., Viikari, J.S., Völker, U., Vollenweider, P., Völzke, H., Vuckovic, D., Waldenberger, M., Wang, J.J., Yang, Q., Chasman, D.I., Tromp, G., Snieder, H., Heid, I.M., Fox, C.S., Köttgen, A., Pattaro, C., Böger, C.A., Fuchsberger, C., Gorski, M., Most, PJV, Teumer, A., Chu, A.Y., Li, M., Mijatovic, V., Nolte, I.M., Cocca, M., Taliun, D., Gomez, F., Li, Y., Tayo, B., Tin, A., Feitosa, M.F., Aspelund, T., Attia, J., Biffar, R., Bochud, M., Boerwinkle, E., Borecki, I., Bottinger, E.P., Chen, M.H., Chouraki, V., Ciullo, M., Coresh, J., Cornelis, M.C., Curhan, G.C., Adamo, A.P., Dehghan, A., Dengler, L., Ding, J., Eiriksdottir, G., Endlich, K., Enroth, S., Esko, T., Franco, O.H., Gasparini, P., Gieger, C., Girotto, G., Gottesman, O., Gudnason, V., Gyllensten, U., Hancock, S.J., Harris, T.B., Helmer, C., Höllerer, S., Hofer, E., Hofman, A., Holliday, E.G., Homuth, G., Hu, F.B., Huth, C., Hutri-Kähönen, N., Hwang, S.J., Imboden, M., Johansson, Å., Kähönen, M., König, W., Kramer, H., Krämer, B.K., Kumar, A., Kutalik, Z., Lambert, J.C., Launer, L.J., Lehtimäki, T., de Borst, M.H., Navis, G., Swertz, M., Liu, Y., Lohman, K., Loos, RJF, Lu, Y., Lyytikäinen, L.P., McEvoy, M.A., Meisinger, C., Meitinger, T., Metspalu, A., Metzger, M., Mihailov, E., Mitchell, P., Nauck, M., Oldehinkel, A.J., Olden, M., Wjh Penninx, B., Pistis, G., Pramstaller, P.P., Probst-Hensch, N., Raitakari, O.T., Rettig, R., Ridker, P.M., Rivadeneira, F., Robino, A., Rosas, S.E., Ruderfer, D., Ruggiero, D., Saba, Y., Sala, C., Schmidt, H., Schmidt, R., Scott, R.J., Sedaghat, S., Smith, A.V., Sorice, R., Stengel, B., Stracke, S., Strauch, K., Toniolo, D., Uitterlinden, A.G., Ulivi, S., Viikari, J.S., Völker, U., Vollenweider, P., Völzke, H., Vuckovic, D., Waldenberger, M., Wang, J.J., Yang, Q., Chasman, D.I., Tromp, G., Snieder, H., Heid, I.M., Fox, C.S., Köttgen, A., Pattaro, C., Böger, C.A., and Fuchsberger, C.

Abstract

This corrects the article DOI: 10.1038/srep45040.

Published
2017

28. Dietary [alfa]-linolenic acid, marine [omega]-3 fatty acids, and mortality in a population with high fish consumption: findings from the PREvención con DIeta MEDiterránea (PREDIMED) study

Author

Ros, E. (Emilio), Estruch, R. (Ramón), Martinez-Gonzalez, M.A. (Miguel Ángel), Salas-Salvado, J. (Jordi), Fito, M. (Montserrat), Corella, D. (Dolores), Martinez, J.A. (José Alfredo), Serra-Majem, L. (Luis), Muñoz, M.A. (Miguel Angel), Fiol, M. (Miquel), Aros, F. (Fernando), Sorli, J.V. (Jose V.), Lopez-Sabater, M.C. (M. Carmen), Serra-Mir, M. (Merce), Bullo, M. (Monica), Sanchez-Tainta, A. (Ana), Hu, F.B. (Frank B.), Guasch-Ferre, M. (Marta), and Sala-Vila, A. (Aleix)

Subjects
PREDIMED, Sudden cardiac death, Ciencias de la Salud::Medicina preventiva [Materias Investigacion], Fish consumption, Fatty acid, Dieta mediterránea, Ciencias de la vida::Metabolismo [Materias Investigacion], Nutrition
Abstract

Epidemiological evidence suggests a cardioprotective role of a-linolenic acid (ALA), a plant-derived x-3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine x-3 fatty acids (long-chain n-3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all-cause and cardiovascular disease mortality. We also examined the effect of meeting the society’s recommendation for long-chain n-3 polyunsaturated fatty acids (≥500 mg/day).

Published
2016

29. Adherence to the Mediterranean dietary pattern and BMI change among U.S. adolescents

Author

Martin-Calvo, N. (Nerea), Chavarro, J.E. (Jorge E.), Falbe, J. (Jennifer), Hu, F.B. (Frank B.), and Field, A.E. (A. E.)

Subjects
Área de Medicina Clínica y Epidemiología
Abstract

Background: Among adults, the Mediterranean dietary pattern (MDP) is inversely related to body mass index (BMI). Data are lacking on adherence to the MDP among youth in the United States and whether the MDP is related to weight change in that group. Objective: To assess whether adherence to the MDP was associated with BMI change among adolescents. To examine temporality, we studied the association between baseline and 2-3-year changes in adherence to the MDP with concurrent changes in BMI, as well as subsequent changes in BMI over a 7-year period. Methods: We prospectively followed 6002 females and 4916 males in the Growing Up Today Study II, aged 8-15 years in 2004, living across United States. Data were collected by questionnaire in 2004, 2006, 2008 and 2011. Dietary intake was assessed by the Youth/Adolescent Questionnaire. The KidMed Index was derived to measure the adherence to the MDP. We used generalized estimating equations with repeated measures within subjects to assess the association between MDP and BMI change. Results: A two-point increment in the KidMed Index was independently associated with a lower gain in BMI (-0.04 kg m(-2); P=0.001). A greater increase in adherence to the KidMed Index was independently related to a lower gain in BMI in both the concurrent (P-for-trend

Published
2016

30. Dietary a-Linolenic acid, Marine x-3 fatty acids, and mortality in a population with high fish consumption: findings from the PREevención con DIeta MEDiterránea (PREDIMED) study

Author

Ros, E. (Emilio), Estruch, R. (Ramón), Martinez-Gonzalez, M.A. (Miguel Ángel), Salas-Salvado, J. (Jordi), Fit, M. (Montserrat), Corella, D. (Dolores), Martinez, J.A. (José Alfredo), Serra-Majem, L. (Luis), Muñoz, M.A. (Miguel Angel), Fiol, M. (Miquel), Aros, F. (Fernando), Sorli, J.V. (Jose V.), Lopez-Sabater, M.C. (M. Carmen), Serra-Mir, M. (Merce), Bullo, M. (Monica), Sanchez-Tainta, A. (Ana), Hu, F.B. (Frank B.), Guasch-Ferre, M. (Marta), and Sala-Vila, A. (Aleix)

Subjects
Sudden cardiac death, Ciencias de la Salud::Medicina preventiva [Materias Investigacion], Fatty acid, Nutrition
Abstract

Epidemiological evidence suggests a cardioprotective role of α‐linolenic acid (ALA), a plant‐derived ω‐3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine x-3 fatty acids (long-chain n-3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all-cause and cardiovascular disease mortality. We also examined the effect of meeting the society’s recommendation for long-chain n-3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results-—We longitudinally evaluated 7202 participants in the PREvenci on con DIeta MEDiterr anea (PREDIMED) trial. Multivariable-adjusted Cox regressionmodels were fitted to estimate hazard ratios. ALA intake correlated towalnut consumption (r=0.94). During a 5.9-y follow-up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios formeeting ALArecommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56–0.92) for all-causemortality and 0.95 (95% CI 0.58–1.57) for fatal cardiovascular disease. The hazard ratios formeeting the recommendation for long-chain n-3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67–1.05) for all-causemortality, 0.61 (95% CI 0.39–0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29–0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22–1.01) for sudden cardiac death. The highest reduction in all-cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45–0.87]). Conclusions-—In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all-cause mortality, whereas protection from cardiac mortality is limited to fish-derived long-chain n-3 polyunsaturated fatty acids.

Published
2016

31. Corrigendum: Rare coding variants and X-linked loci associated with age at menarche

Author

Lunetta, K.L., Day, F.R., Sulem, P., Ruth, K.S., Tung, J.Y., Hinds, D.A., Esko, T., Elks, C.E., Altmaier, E., He, C., Huffman, J.E., Mihailov, E., Porcu, E., Robino, A., Rose, L.M., Schick, U.M., Stolk, L., Teumer, A., Thompson, D.J., Traglia, M., Wang, C.A., Yerges-Armstrong, L.M., Antoniou, A.C., Barbieri, C., Coviello, A.D., Cucca, F., Demerath, E.W., Dunning, A.M., Gandin, I., Grove, M.L., Gudbjartsson, D.F., Hocking, L.J., Hofman, A., Huang, J., Jackson, R.D., Karasik, D., Kriebel, J., Lange, E.M., Lange, L.A., Langenberg, C., Li, X., Luan, J., Mägi, R., Morrison, A.C., Padmanabhan, S., Pirie, A., Polasek, O., Porteous, D.J., Reiner, A.P., Rivadeneira, F., Rudan, I., Sala, C.F., Schlessinger, D., Scott, R.A., Stöckl, D., Visser, J.A., Völker, U., Vozzi, D., Wilson, J.G., Zygmunt, M., EPIC-Interact Consortium (), Generation Scotland Consortium (), Boerwinkle, E., Buring, J.E., Crisponi, L., Easton, D.F., Hayward, C., Hu, F.B., Liu, S., Metspalu, A., Pennell, C.E., Ridker, P.M., Strauch, K., Streeten, E.A., Toniolo, D., Uitterlinden, A.G., Ulivi, S., Völzke, H., Wareham, N.J., Wellons, M., Franceschini, N., Chasman, D.I., Thorsteinsdottir, U., Murray, A., Stefansson, K., Murabito, J.M., Ong, K.K., and Perry, J.R.

Subjects
Adult, Adolescent, Genotype, Mutation, Missense, Immunoglobulins, Cell Cycle Proteins, Penetrance, AMP-Activated Protein Kinases, Autoantigens, White People, Young Adult, Gene Frequency, Genes, X-Linked, Humans, Aged, Menarche, Chromosomes, Human, X, Hypogonadism, Fatty Acids, Age Factors, Genetic Variation, Membrane Proteins, Proteins, RNA-Binding Proteins, Receptors, Neurokinin-3, Middle Aged, Corrigenda, Amides, Phenotype, Codon, Nonsense, Female, RNA Interference, Laminin, Energy Metabolism, Signal Transduction
Abstract

More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only ∼3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency protein-coding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P5 × 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P=9.4 × 10(-13)) and FAAH2 (rs5914101, P=4.9 × 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P=2.8 × 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain ∼0.5% variance, indicating that these overlooked sources of variation do not substantially explain the 'missing heritability' of this complex trait.

Published
2015

32. Parental origin of sequence variants associated with complex diseases

Author

Voight, B.F., Raychaudhuri, S., Purcell, S., McCarroll, S.A., Segrè, A.V., Ardlie, K., Burtt, N.P., Crawford, G., Elliott, A.L., Green, T., Guiducci, C., Saxena, R., Daly, M.J., Florez, J.C., Altshuler, D., Meigs, J.B., Scott, L.J., Welch, R.P., Willer, C.J., Ganser, M., Jackson, A.U., Stringham, H.M., Abecasis, G.R., Boehnke, M., Steinthorsdottir, V., Thorleifsson, G., Kong, A., Walters, G.B., Thorsteinsdottir, U., Stefansson, K., Dina, C., Proença, C., Cauchi, S., Froguel, P., Zeggini, E., Bumpstead, S., Payne, F., Smith, N., Barroso, I., Ferreira, T., Elliott, K.S., Lindgren, C.M., Prokopenko, I., Rayner, N.W., Robertson, N.R., Morris, A.P., McCarthy, M.I., Huth, C., Grallert, H., Gieger, C., Klopp, N., Meitinger, T., Petersen, A.-K., Thorand, B., Wichmann, H.-E., Illig, T., Aulchenko, Y.S., Amin, N., Witteman, J., Hofman, A., Van Duijn, C.M., McCulloch, L.J., Bennett, A.J., Groves, C.J., Hassanali, N., Owen, K.R., Gloyn, A.L., Wu, G., Stein, L.D., Langenberg, C., Griffin, S., Wareham, N.J., Hoffmann, O.M., Hide, W.A., Dupuis, J., Qi, L., Kraft, P., Sun, Q., Hunter, D., Hu, F.B., Cornelis, M., VanDam, R., Van Hoek, M., Van Herpt, T., Sijbrands, E., Uitterlinden, A., Navarro, P., Balkau, B., Benediktsson, R., Sigurdsson, G., Blagieva, R., Boehm, B.O., Boerwinkle, E., Bonnycastle, L.L., Chines, P.S., Erdos, M.R., Morken, M.A., Narisu, N., Swift, A.J., Boström, K.B., Bravenboer, B., Charpentier, G., Couper, D.J., Doney, A.S.F., Morris, A.D., Palmer, C.N.A., Fox, C.S., Franklin, C.S., Rudan, I., Grarup, N., Hadjadj, S., Thomas Sparsø, [No Value], Campbell, H., Wilson, J.F., Hansen, T., Pedersen, O., Herder, C., Roden, M., Isomaa, B., Tuomi, T., Johnson, P.R.V., Jørgensen, T., Kao, W.H.L., Kuusisto, J., Laakso, M., Lauritzen, T., Li, M., Lieverse, A., Lyssenko, V., Nilsson, P., Groop, L., Marre, M., Midthjell, K., Platou, C., Hveem, K., Perry, J.R.B., Shields, B.M., Weedon, M.N., Frayling, T.M., Hattersley, A.T., Rathmann, W., Strassburger, K., Rocheleau, G., Sladek, R., Sampson, M.J., Shrader, P., Tichet, J., Bergman, R.N., Collins, F.S., Gyllensten, U., Hitman, G.A., Mohlke, K.L., Pramstaller, P.P., Tuomilehto, J., Walker, M., Watanabe, R.M., Pankow, J.S., and deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland. kong@decode.is

Subjects
Male, CCCTC-Binding Factor, Iceland, Mothers, Breast Neoplasms, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Fathers, Genomic Imprinting, 03 medical and health sciences, 0302 clinical medicine, Polymorphism (computer science), Humans, SNP, Genetic Predisposition to Disease, Allele, Alleles, 030304 developmental biology, Genetics, 0303 health sciences, Binding Sites, Multidisciplinary, Genome, Human, Chromosomes, Human, Pair 11, Haplotype, DNA Methylation, Pedigree, Repressor Proteins, Diabetes Mellitus, Type 2, Haplotypes, Carcinoma, Basal Cell, DNA methylation, Female, Human genome, Genomic imprinting, Chromosomes, Human, Pair 7, 030217 neurology & neurosurgery
Abstract

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field Effects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined. For this we used a combination of genealogy and long-range phasing. We then focused on SNPs that associate with diseases and are within 500 kilobases of known imprinted genes. Seven independent SNP associations were examined. Five-one with breast cancer, one with basal-cell carcinoma and three with type 2 diabetes-have parental-origin-specific associations. These variants are located in two genomic regions, 11p15 and 7q32, each harbouring a cluster of imprinted genes. Furthermore, we observed a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes. Here the allele that confers risk when paternally inherited is protective when maternally transmitted. We identified a differentially methylated CTCF-binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site. info:eu-repo/grantAgreement/EC/FP7/218071

Published
2009

33. Association of Cardiometabolic Multimorbidity With Mortality The Emerging Risk Factors Collaboration

Author

Angelantonio, E. di, Kaptoge, S., Wormser, D., Willeit, P., Butterworth, A.S., Bansal, N., O'Keeffe, L.M., Gao, P., Wood, A.M., Burgess, S., Freitag, D.F., Pennells, L., Peters, S.A., Hart, C.L., Haheim, L.L., Gillum, R.F., Nordestgaard, B.G., Psaty, B.M., Yeap, B.B., Knuiman, M.W., Nietert, P.J., Kauhanen, J., Salonen, J.T., Kuller, L.H., Simons, L.A., Schouw, Y.T. van der, Barrett-Connor, E., Selmer, R., Crespo, C.J., Rodriguez, B., Verschuren, W.M.M., Salomaa, V., Svardsudd, K., Harst, P. van der, Bjorkelund, C., Wilhelmsen, L., Wallace, R.B., Brenner, H., Amouyel, P., Barr, E.L.M., Iso, H., Onat, A., Trevisan, M., D'Agostino, R.B., Cooper, C., Kavousi, M., Welin, L., Roussel, R., Hu, F.B., Sato, S., Davidson, K.W., Howard, B.V., Leening, M., Rosengren, A., Dorr, M., Deeg, D.J.H., Kiechl, S., Stehouwer, C.D.A., Nissinen, A., Giampaoli, S., Donfrancesco, C., Kromhout, D., Price, J.F., Peters, A., Meade, T.W., Casiglia, E., Lawlor, D.A., Gallacher, J., Nagel, D., Franco, O.H., Assmann, G., Dagenais, G.R., Jukema, J.W., Sundstrom, J., Woodward, M., Brunner, E.J., Khaw, K.T., Wareham, N.J., Whitsel, E.A., Njolstad, I., Hedblad, B., Wassertheil-Smoller, S., Engstrom, G., Rosamond, W.D., Selvin, E., Sattar, N., Thompson, S.G., Danesh, J., and Emerging Risk Factors Collaboratio

Published
2015

34. Genetic variation in FTO and mortality

Author

Zimmermann, E., Angquist, L.H., Mirza, S.S., Zhao, J.H., Chasman, D.I., Fischer, K., Qi, Q., Smith, A.V., Thinggaard, M., Jarczok, M.N., Nalls, M.A., Trompet, S., Timpson, N.J., Schmidt, B., Jackson, A.U., Lyytikainen, L.P., Verweij, N., Mueller-Nurasyid, M., Vikstrom, M., Marques-Vidal, P., Wong, A., Meidtner, K., Middelberg, R.P., Strawbridge, R.J., Christiansen, L., Kyvik, K.O., Hamsten, A., Jaaskelainen, T., Tjonneland, A., Eriksson, J.G., Whitfield, J.B., Boeing, H., Hardy, R., Vollenweider, P., Leander, K., Peters, A., Harst, P. van der, Kumari, M., Lehtimaki, T., Meirhaeghe, A., Tuomilehto, J., Jockel, K.H., Ben-Shlomo, Y., Sattar, N., Baumeister, S.E., Smith, G.D., Casas, J.P., Houston, D.K., Marz, W., Christensen, K., Gudnason, V., Hu, F.B., Metspalu, A., Ridker, P.M., Wareham, N.J., Loos, R.J.F., Tiemeier, H., Sonestedt, E., Sorensen, T.I.A., The FTO-Mortality Collaborating, Epidemiology, Surgery, Erasmus MC other, Child and Adolescent Psychiatry / Psychology, FTO-Mortality Collaborating Group, Orho-Melander, M., Zillikens, C., Ikram, A., Hofman, A., Luan, J., Khaw, KT., Rose, LM., Läll, K., Mägi, R., Qi, L., Sun, Q., Harris, TB., Launer, LJ., Eiriksdottir, G., Kleber, ME., Delgado, G., Liu, Y., Garcia, M., Teumer, A., Grabe, H., Homuth, G., Jukema, JW., Ford, I., de Craen AJ., Gallacher, J., Yarnell, J., Mahabadi, AA., Nöthen, MM., Erbel, R., Stringham, HM., Boehnke, M., Amouyel, P., Ferrières, J., Arveiler, D., Kähönen, M., Nikus, K., Nieminen, T., Sanchez, A., Kivimaki, M., van Vliet-Ostaptchouk JV., Hampel, R., Thorand, B., De Faire, U., Nyberg, F., Kuh, D., Martin, NG., Montgomery, GW., Heath, AC., Madden, PA., Osmond, C., Pulizzi, N., Roswall, N., Halkjaer, J., Overvad, K., Uusitupa, M., Kinnunen, L., Lindström, J., Saramies, J., Keinänen-Kiukaanniemi, S., Uusitalo, H., Hussi, E., Baldassarre, D., Veglia, F., Humphries, S., Tremoli, E., and Heitmann, B.

Subjects
obesity, nutritional and metabolic diseases, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Genetic Variation, Proteins, mortality, Polymorphism, Single Nucleotide, Article, Body Mass Index, meta-analysis, Observational Studies as Topic, Humans, Genetic Predisposition to Disease, Waist Circumference, FTO, Adiposity, Genome-Wide Association Study
Abstract

Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m(-2) ; 95% CI 0.28-0.32, P

Published
2015

35. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Author

ICBP Consortium, AGEN Consortium, CHARGe-Heart Failure Group, ECHOGen Consortium, CARDIOGRAM, Abecasis, GR., Adair, LS., Alexander, M., Altshuler, D., Amin, N., Arking, DE., Arora, P., Aulchenko, Y., Bakker, SJ., Bandinelli, S., Barroso, I., Beckmann, JS., Beilby, JP., Bergman, RN., Bergmann, S., Bis, JC., Boehnke, M., Bonnycastle, LL., Bornstein, SR., Bots, ML., Bragg-Gresham, JL., Brand, SM., Brand, E., Braund, PS., Brown, MJ., Burton, PR., Casas, JP., Caulfield, MJ., Chakravarti, A., Chambers, JC., Chandak, GR., Chang, YP., Charchar, FJ., Chaturvedi, N., Shin Cho, Y., Clarke, R., Collins, FS., Collins, R., Connell, JM., Cooper, JA., Cooper, MN., Cooper, RS., Corsi, AM., Dörr, M., Dahgam, S., Danesh, J., Davey Smith, G., Day, IN., Deloukas, P., Denniff, M., Dominiczak, AF., Dong, Y., Doumatey, A., Elliott, P., Elosua, R., Erdmann, J., Eyheramendy, S., Farrall, M., Fava, C., Forrester, T., Fowkes, FG., Fox, ER., Frayling, TM., Galan, P., Ganesh, SK., Garcia, M., Gaunt, TR., Glazer, NL., Go, MJ., Goel, A., Grässler, J., Grobbee, DE., Groop, L., Guarrera, S., Guo, X., Hadley, D., Hamsten, A., Han, BG., Hardy, R., Hartikainen, AL., Heath, S., Heckbert, SR., Hedblad, B., Hercberg, S., Hernandez, D., Hicks, AA., Hilton, G., Hingorani, AD., Bolton, JA., Hopewell, JC., Howard, P., Humphries, SE., Hunt, SC., Hveem, K., Ikram, MA., Islam, M., Iwai, N., Jarvelin, MR., Jackson, AU., Jafar, TH., Janipalli, CS., Johnson, T., Kathiresan, S., Khaw, KT., Kim, HL., Kinra, S., Kita, Y., Kivimaki, M., Kooner, JS., Kumar, MJ., Kuh, D., Kulkarni, SR., Kumari, M., Kuusisto, J., Kuznetsova, T., Laakso, M., Laan, M., Laitinen, J., Lakatta, EG., Langefeld, CD., Larson, MG., Lathrop, M., Lawlor, DA., Lawrence, RW., Lee, JY., Lee, NR., Levy, D., Li, Y., Longstreth, WT., Luan£££Jian'an£££ J., Lucas, G., Ludwig, B., Mangino, M., Mani, KR., Marmot, MG., Mattace-Raso, FU., Matullo, G., McArdle, WL., McKenzie, CA., Meitinger, T., Melander, O., Meneton, P., Meschia, JF., Miki, T., Milaneschi, Y., Mohlke, KL., Mooser, V., Morken, MA., Morris, RW., Mosley, TH., Najjar, S., Narisu, N., Newton-Cheh, C., Nguyen, KD., Nilsson, P., Nyberg, F., O'Donnell, CJ., Ogihara, T., Ohkubo, T., Okamura, T., Ong, RT., Ongen, H., Onland-Moret, NC., O'Reilly, PF., Org, E., Orru, M., Palmas, W., Palmen, J., Palmer, LJ., Palmer, ND., Parker, AN., Peden, JF., Peltonen, L., Perola, M., Pihur, V., Platou, CG., Plump, A., Prabhakaran, D., Psaty, BM., Raffel, LJ., Rao, DC., Rasheed, A., Ricceri, F., Rice, KM., Rosengren, A., Rotter, JI., Rudock, ME., Sõber, S., Salako, T., Saleheen, D., Salomaa, V., Samani, NJ., Schwartz, SM., Schwarz, PE., Scott, LJ., Scott, J., Scuteri, A., Sehmi, JS., Seielstad, M., Seshadri, S., Sharma, P., Shaw-Hawkins, S., Shi, G., Shrine, NR., Sijbrands, EJ., Sim, X., Singleton, A., Sjögren, M., Smith, NL., Soler Artigas, M., Spector, TD., Staessen, JA., Stancakova, A., Steinle, NI., Strachan, DP., Stringham, HM., Sun, YV., Swift, AJ., Tabara, Y., Tai, ES., Talmud, PJ., Taylor, A., Terzic, J., Thelle, DS., Tobin, MD., Tomaszewski, M., Tripathy, V., Tuomilehto, J., Tzoulaki, I., Uda, M., Ueshima, H., Uiterwaal, CS., Umemura, S., van der Harst, P., van der Schouw YT., van Gilst WH., Vartiainen, E., Vasan, RS., Veldre, G., Verwoert, GC., Viigimaa, M., Vinay, DG., Vineis, P., Voight, BF., Vollenweider, P., Wagenknecht, LE., Wain, LV., Wang, X., Wang, TJ., Wareham, NJ., Watkins, H., Weder, AB., Whincup, PH., Wiggins, KL., Witteman, JC., Wong, A., Wu, Y., Yajnik, CS., Yao, J., Young, JH., Zelenika, D., Zhai, G., Zhang, W., Zhang, F., Zhao, JH., Zhu, H., Zhu, X., Zitting, P., Zukowska-Szczechowska, E., Okada, Y., Wu, JY., Gu, D., Takeuchi, F., Takahashi, A., Maeda, S., Tsunoda, T., Chen, P., Lim, SC., Wong, TY., Liu, J., Young, TL., Aung, T., Teo, YY., Kim, YJ., Kang, D., Chen, CH., Tsai, FJ., Chang, LC., Fann, SJ., Mei, H., Hixson, JE., Chen, S., Katsuya, T., Isono, M., Albrecht, E., Yamamoto, K., Kubo, M., Nakamura, Y., Kamatani, N., Kato, N., He, J., Chen, YT., Tanaka, T., Reilly, MP., Schunkert, H., Assimes, TL., Hall, A., Hengstenberg, C., König, IR., Laaksonen, R., McPherson, R., Thompson, JR., Thorsteinsdottir, U., Ziegler, A., Absher, D., Chen, L., Cupples, LA., Halperin, E., Li, M., Musunuru, K., Preuss, M., Schillert, A., Thorleifsson, G., Wells, GA., Holm, H., Roberts, R., Stewart, AF., Fortmann, S., Go, A., Hlatky, M., Iribarren, C., Knowles, J., Myers, R., Quertermous, T., Sidney, S., Risch, N., Tang, H., Blankenberg, S., Schnabel, R., Sinning, C., Lackner, KJ., Tiret, L., Nicaud, V., Cambien, F., Bickel, C., Rupprecht, HJ., Perret, C., Proust, C., Münzel, TF., Barbalic, M., Chen, IY., Demissie-Banjaw, S., Folsom, A., Lumley, T., Marciante, K., Taylor, KD., Volcik, K., Gretarsdottir, S., Gulcher, JR., Kong, A., Stefansson, K., Thorgeirsson, G., Andersen, K., Fischer, M., Grosshennig, A., Linsel-Nitschke, P., Stark, K., Schreiber, S., Aherrahrou, Z., Bruse, P., Doering, A., Klopp, N., Diemert, P., Loley, C., Medack, A., Nahrstedt, J., Peters, A., Wagner, AK., Willenborg, C., Böhm, BO., Dobnig, H., Grammer, TB., Hoffmann, MM., Meinitzer, A., Winkelmann, BR., Pilz, S., Renner, W., Scharnagl, H., Stojakovic, T., Tomaschitz, A., Winkler, K., Guiducci, C., Burtt, N., Gabriel, SB., Dandona, S., Jarinova, O., Qu, L., Wilensky, R., Matthai, W., Hakonarson, HH., Devaney, J., Burnett, MS., Pichard, AD., Kent, KM., Satler, L., Lindsay, JM., Waksman, R., Knouff, CW., Waterworth, DM., Walker, MC., Epstein, SE., Rader, DJ., Nelson, CP., Wright, BJ., Balmforth, AJ., Ball, SG., Loehr, LR., Rosamond, WD., Benjamin, E., Haritunians, T., Couper, D., Murabito, J., Wang, YA., Stricker, BH., Chang, PP., Willerson, JT., Felix, SB., Watzinger, N., Aragam, J., Zweiker, R., Lind, L., Rodeheffer, RJ., Greiser, KH., Deckers, JW., Stritzke, J., Ingelsson, E., Kullo, I., Haerting, J., Reffelmann, T., Redfield, MM., Werdan, K., Mitchell, GF., Arnett, DK., Gottdiener, JS., Blettner, M., Friedrich, N., Pattaro, C., Teumer, A., Gorski, M., Chu, A.Y., Mijatovic, V., Garnaas, M., Tin, A., Sorice, R., Taliun, D., Olden, M., Foster, M., Yang, Q., Chen, M.H., Pers, T.H., Johnson, A.D., Ko, Y.A., Fuchsberger, C., Tayo, B., Nalls, M., Feitosa, M.F., Isaacs, A., Dehghan, A., d'Adamo, P., Adeyemo, A., Dieffenbach, A.K., Zonderman, A.B., Nolte, I.M., van der Most, P.J., Wright, A.F., Shuldiner, A.R., Morrison, A.C., Hofman, A., Smith, A.V., Dreisbach, A.W., Franke, A., Uitterlinden, A.G., Metspalu, A., Tonjes, A., Lupo, A., Robino, A., Johansson, Å., Demirkan, A., Kollerits, B., Freedman, B.I., Ponte, B., Oostra, B.A., Paulweber, B., Krämer, B.K., Mitchell, B.D., Buckley, B.M., Peralta, C.A., Hayward, C., Helmer, C., Rotimi, C.N., Shaffer, C.M., Müller, C., Sala, C., van Duijn, C.M., Saint-Pierre, A., Ackermann, D., Shriner, D., Ruggiero, D., Toniolo, D., Lu, Y., Cusi, D., Czamara, D., Ellinghaus, D., Siscovick, D.S., Ruderfer, D., Gieger, C., Grallert, H., Rochtchina, E., Atkinson, E.J., Holliday, E.G., Boerwinkle, E., Salvi, E., Bottinger, E.P., Murgia, F., Rivadeneira, F., Ernst, F., Kronenberg, F., Hu, F.B., Navis, G.J., Curhan, G.C., Ehret, G.B., Homuth, G., Coassin, S., Thun, G.A., Pistis, G., Gambaro, G., Malerba, G., Montgomery, G.W., Eiriksdottir, G., Jacobs, G., Li, G., Wichmann, H.E., Campbell, H., Schmidt, H., Wallaschofski, H., Völzke, H., Brenner, H., Kroemer, H.K., Kramer, H., Lin, H., Leach, I.M., Ford, I., Guessous, I., Rudan, I., Prokopenko, I., Borecki, I., Heid, I.M., Kolcic, I., Persico, I., Jukema, J.W., Wilson, J.F., Felix, J.F., Divers, J., Lambert, J.C., Stafford, J.M., Gaspoz, J.M., Smith, J.A., Faul, J.D., Wang, J.J., Ding, J., Hirschhorn, J.N., Attia, J., Whitfield, J.B., Chalmers, J., Viikari, J., Coresh, J., Denny, J.C., Karjalainen, J., Fernandes, J.K., Endlich, K., Butterbach, K., Keene, K.L., Lohman, K., Portas, L., Launer, L.J., Lyytikäinen, L.P., Yengo, L., Franke, L., Ferrucci, L., Rose, L.M., Kedenko, L., Rao, M., Struchalin, M., Kleber, M.E., Cavalieri, M., Haun, M., Cornelis, M.C., Ciullo, M., Pirastu, M., de Andrade, M., McEvoy, M.A., Woodward, M., Adam, M., Cocca, M., Nauck, M., Imboden, M., Waldenberger, M., Pruijm, M., Metzger, M., Stumvoll, M., Evans, M.K., Sale, M.M., Kähönen, M., Boban, M., Bochud, M., Rheinberger, M., Verweij, N., Bouatia-Naji, N., Martin, N.G., Hastie, N., Probst-Hensch, N., Soranzo, N., Devuyst, O., Raitakari, O., Gottesman, O., Franco, O.H., Polasek, O., Gasparini, P., Munroe, P.B., Ridker, P.M., Mitchell, P., Muntner, P., Meisinger, C., Smit, J.H., Kovacs, P., Wild, P.S., Froguel, P., Rettig, R., Mägi, R., Biffar, R., Schmidt, R., Middelberg, R.P., Carroll, R.J., Penninx, B.W., Scott, R.J., Katz, R., Sedaghat, S., Wild, S.H., Kardia, S.L., Ulivi, S., Hwang, S.J., Enroth, S., Kloiber, S., Trompet, S., Stengel, B., Hancock, S.J., Turner, S.T., Rosas, S.E., Stracke, S., Harris, T.B., Zeller, T., Zemunik, T., Lehtimäki, T., Illig, T., Aspelund, T., Nikopensius, T., Esko, T., Gyllensten, U., Völker, U., Emilsson, V., Vitart, V., Aalto, V., Gudnason, V., Chouraki, V., Chen, W.M., Igl, W., März, W., Koenig, W., Lieb, W., Loos, R.J., Liu, Y., Snieder, H., Pramstaller, P.P., Parsa, A., O'Connell, J.R., Susztak, K., Hamet, P., Tremblay, J., de Boer, I.H., Böger, C.A., Goessling, W., Chasman, D.I., Köttgen, A., Kao, W.H., Fox, C.S., ICBP Consortium, AGEN Consortium, CHARGe-Heart Failure Group, ECHOGen Consortium, CARDIOGRAM, Abecasis, GR., Adair, LS., Alexander, M., Altshuler, D., Amin, N., Arking, DE., Arora, P., Aulchenko, Y., Bakker, SJ., Bandinelli, S., Barroso, I., Beckmann, JS., Beilby, JP., Bergman, RN., Bergmann, S., Bis, JC., Boehnke, M., Bonnycastle, LL., Bornstein, SR., Bots, ML., Bragg-Gresham, JL., Brand, SM., Brand, E., Braund, PS., Brown, MJ., Burton, PR., Casas, JP., Caulfield, MJ., Chakravarti, A., Chambers, JC., Chandak, GR., Chang, YP., Charchar, FJ., Chaturvedi, N., Shin Cho, Y., Clarke, R., Collins, FS., Collins, R., Connell, JM., Cooper, JA., Cooper, MN., Cooper, RS., Corsi, AM., Dörr, M., Dahgam, S., Danesh, J., Davey Smith, G., Day, IN., Deloukas, P., Denniff, M., Dominiczak, AF., Dong, Y., Doumatey, A., Elliott, P., Elosua, R., Erdmann, J., Eyheramendy, S., Farrall, M., Fava, C., Forrester, T., Fowkes, FG., Fox, ER., Frayling, TM., Galan, P., Ganesh, SK., Garcia, M., Gaunt, TR., Glazer, NL., Go, MJ., Goel, A., Grässler, J., Grobbee, DE., Groop, L., Guarrera, S., Guo, X., Hadley, D., Hamsten, A., Han, BG., Hardy, R., Hartikainen, AL., Heath, S., Heckbert, SR., Hedblad, B., Hercberg, S., Hernandez, D., Hicks, AA., Hilton, G., Hingorani, AD., Bolton, JA., Hopewell, JC., Howard, P., Humphries, SE., Hunt, SC., Hveem, K., Ikram, MA., Islam, M., Iwai, N., Jarvelin, MR., Jackson, AU., Jafar, TH., Janipalli, CS., Johnson, T., Kathiresan, S., Khaw, KT., Kim, HL., Kinra, S., Kita, Y., Kivimaki, M., Kooner, JS., Kumar, MJ., Kuh, D., Kulkarni, SR., Kumari, M., Kuusisto, J., Kuznetsova, T., Laakso, M., Laan, M., Laitinen, J., Lakatta, EG., Langefeld, CD., Larson, MG., Lathrop, M., Lawlor, DA., Lawrence, RW., Lee, JY., Lee, NR., Levy, D., Li, Y., Longstreth, WT., Luan£££Jian'an£££ J., Lucas, G., Ludwig, B., Mangino, M., Mani, KR., Marmot, MG., Mattace-Raso, FU., Matullo, G., McArdle, WL., McKenzie, CA., Meitinger, T., Melander, O., Meneton, P., Meschia, JF., Miki, T., Milaneschi, Y., Mohlke, KL., Mooser, V., Morken, MA., Morris, RW., Mosley, TH., Najjar, S., Narisu, N., Newton-Cheh, C., Nguyen, KD., Nilsson, P., Nyberg, F., O'Donnell, CJ., Ogihara, T., Ohkubo, T., Okamura, T., Ong, RT., Ongen, H., Onland-Moret, NC., O'Reilly, PF., Org, E., Orru, M., Palmas, W., Palmen, J., Palmer, LJ., Palmer, ND., Parker, AN., Peden, JF., Peltonen, L., Perola, M., Pihur, V., Platou, CG., Plump, A., Prabhakaran, D., Psaty, BM., Raffel, LJ., Rao, DC., Rasheed, A., Ricceri, F., Rice, KM., Rosengren, A., Rotter, JI., Rudock, ME., Sõber, S., Salako, T., Saleheen, D., Salomaa, V., Samani, NJ., Schwartz, SM., Schwarz, PE., Scott, LJ., Scott, J., Scuteri, A., Sehmi, JS., Seielstad, M., Seshadri, S., Sharma, P., Shaw-Hawkins, S., Shi, G., Shrine, NR., Sijbrands, EJ., Sim, X., Singleton, A., Sjögren, M., Smith, NL., Soler Artigas, M., Spector, TD., Staessen, JA., Stancakova, A., Steinle, NI., Strachan, DP., Stringham, HM., Sun, YV., Swift, AJ., Tabara, Y., Tai, ES., Talmud, PJ., Taylor, A., Terzic, J., Thelle, DS., Tobin, MD., Tomaszewski, M., Tripathy, V., Tuomilehto, J., Tzoulaki, I., Uda, M., Ueshima, H., Uiterwaal, CS., Umemura, S., van der Harst, P., van der Schouw YT., van Gilst WH., Vartiainen, E., Vasan, RS., Veldre, G., Verwoert, GC., Viigimaa, M., Vinay, DG., Vineis, P., Voight, BF., Vollenweider, P., Wagenknecht, LE., Wain, LV., Wang, X., Wang, TJ., Wareham, NJ., Watkins, H., Weder, AB., Whincup, PH., Wiggins, KL., Witteman, JC., Wong, A., Wu, Y., Yajnik, CS., Yao, J., Young, JH., Zelenika, D., Zhai, G., Zhang, W., Zhang, F., Zhao, JH., Zhu, H., Zhu, X., Zitting, P., Zukowska-Szczechowska, E., Okada, Y., Wu, JY., Gu, D., Takeuchi, F., Takahashi, A., Maeda, S., Tsunoda, T., Chen, P., Lim, SC., Wong, TY., Liu, J., Young, TL., Aung, T., Teo, YY., Kim, YJ., Kang, D., Chen, CH., Tsai, FJ., Chang, LC., Fann, SJ., Mei, H., Hixson, JE., Chen, S., Katsuya, T., Isono, M., Albrecht, E., Yamamoto, K., Kubo, M., Nakamura, Y., Kamatani, N., Kato, N., He, J., Chen, YT., Tanaka, T., Reilly, MP., Schunkert, H., Assimes, TL., Hall, A., Hengstenberg, C., König, IR., Laaksonen, R., McPherson, R., Thompson, JR., Thorsteinsdottir, U., Ziegler, A., Absher, D., Chen, L., Cupples, LA., Halperin, E., Li, M., Musunuru, K., Preuss, M., Schillert, A., Thorleifsson, G., Wells, GA., Holm, H., Roberts, R., Stewart, AF., Fortmann, S., Go, A., Hlatky, M., Iribarren, C., Knowles, J., Myers, R., Quertermous, T., Sidney, S., Risch, N., Tang, H., Blankenberg, S., Schnabel, R., Sinning, C., Lackner, KJ., Tiret, L., Nicaud, V., Cambien, F., Bickel, C., Rupprecht, HJ., Perret, C., Proust, C., Münzel, TF., Barbalic, M., Chen, IY., Demissie-Banjaw, S., Folsom, A., Lumley, T., Marciante, K., Taylor, KD., Volcik, K., Gretarsdottir, S., Gulcher, JR., Kong, A., Stefansson, K., Thorgeirsson, G., Andersen, K., Fischer, M., Grosshennig, A., Linsel-Nitschke, P., Stark, K., Schreiber, S., Aherrahrou, Z., Bruse, P., Doering, A., Klopp, N., Diemert, P., Loley, C., Medack, A., Nahrstedt, J., Peters, A., Wagner, AK., Willenborg, C., Böhm, BO., Dobnig, H., Grammer, TB., Hoffmann, MM., Meinitzer, A., Winkelmann, BR., Pilz, S., Renner, W., Scharnagl, H., Stojakovic, T., Tomaschitz, A., Winkler, K., Guiducci, C., Burtt, N., Gabriel, SB., Dandona, S., Jarinova, O., Qu, L., Wilensky, R., Matthai, W., Hakonarson, HH., Devaney, J., Burnett, MS., Pichard, AD., Kent, KM., Satler, L., Lindsay, JM., Waksman, R., Knouff, CW., Waterworth, DM., Walker, MC., Epstein, SE., Rader, DJ., Nelson, CP., Wright, BJ., Balmforth, AJ., Ball, SG., Loehr, LR., Rosamond, WD., Benjamin, E., Haritunians, T., Couper, D., Murabito, J., Wang, YA., Stricker, BH., Chang, PP., Willerson, JT., Felix, SB., Watzinger, N., Aragam, J., Zweiker, R., Lind, L., Rodeheffer, RJ., Greiser, KH., Deckers, JW., Stritzke, J., Ingelsson, E., Kullo, I., Haerting, J., Reffelmann, T., Redfield, MM., Werdan, K., Mitchell, GF., Arnett, DK., Gottdiener, JS., Blettner, M., Friedrich, N., Pattaro, C., Teumer, A., Gorski, M., Chu, A.Y., Mijatovic, V., Garnaas, M., Tin, A., Sorice, R., Taliun, D., Olden, M., Foster, M., Yang, Q., Chen, M.H., Pers, T.H., Johnson, A.D., Ko, Y.A., Fuchsberger, C., Tayo, B., Nalls, M., Feitosa, M.F., Isaacs, A., Dehghan, A., d'Adamo, P., Adeyemo, A., Dieffenbach, A.K., Zonderman, A.B., Nolte, I.M., van der Most, P.J., Wright, A.F., Shuldiner, A.R., Morrison, A.C., Hofman, A., Smith, A.V., Dreisbach, A.W., Franke, A., Uitterlinden, A.G., Metspalu, A., Tonjes, A., Lupo, A., Robino, A., Johansson, Å., Demirkan, A., Kollerits, B., Freedman, B.I., Ponte, B., Oostra, B.A., Paulweber, B., Krämer, B.K., Mitchell, B.D., Buckley, B.M., Peralta, C.A., Hayward, C., Helmer, C., Rotimi, C.N., Shaffer, C.M., Müller, C., Sala, C., van Duijn, C.M., Saint-Pierre, A., Ackermann, D., Shriner, D., Ruggiero, D., Toniolo, D., Lu, Y., Cusi, D., Czamara, D., Ellinghaus, D., Siscovick, D.S., Ruderfer, D., Gieger, C., Grallert, H., Rochtchina, E., Atkinson, E.J., Holliday, E.G., Boerwinkle, E., Salvi, E., Bottinger, E.P., Murgia, F., Rivadeneira, F., Ernst, F., Kronenberg, F., Hu, F.B., Navis, G.J., Curhan, G.C., Ehret, G.B., Homuth, G., Coassin, S., Thun, G.A., Pistis, G., Gambaro, G., Malerba, G., Montgomery, G.W., Eiriksdottir, G., Jacobs, G., Li, G., Wichmann, H.E., Campbell, H., Schmidt, H., Wallaschofski, H., Völzke, H., Brenner, H., Kroemer, H.K., Kramer, H., Lin, H., Leach, I.M., Ford, I., Guessous, I., Rudan, I., Prokopenko, I., Borecki, I., Heid, I.M., Kolcic, I., Persico, I., Jukema, J.W., Wilson, J.F., Felix, J.F., Divers, J., Lambert, J.C., Stafford, J.M., Gaspoz, J.M., Smith, J.A., Faul, J.D., Wang, J.J., Ding, J., Hirschhorn, J.N., Attia, J., Whitfield, J.B., Chalmers, J., Viikari, J., Coresh, J., Denny, J.C., Karjalainen, J., Fernandes, J.K., Endlich, K., Butterbach, K., Keene, K.L., Lohman, K., Portas, L., Launer, L.J., Lyytikäinen, L.P., Yengo, L., Franke, L., Ferrucci, L., Rose, L.M., Kedenko, L., Rao, M., Struchalin, M., Kleber, M.E., Cavalieri, M., Haun, M., Cornelis, M.C., Ciullo, M., Pirastu, M., de Andrade, M., McEvoy, M.A., Woodward, M., Adam, M., Cocca, M., Nauck, M., Imboden, M., Waldenberger, M., Pruijm, M., Metzger, M., Stumvoll, M., Evans, M.K., Sale, M.M., Kähönen, M., Boban, M., Bochud, M., Rheinberger, M., Verweij, N., Bouatia-Naji, N., Martin, N.G., Hastie, N., Probst-Hensch, N., Soranzo, N., Devuyst, O., Raitakari, O., Gottesman, O., Franco, O.H., Polasek, O., Gasparini, P., Munroe, P.B., Ridker, P.M., Mitchell, P., Muntner, P., Meisinger, C., Smit, J.H., Kovacs, P., Wild, P.S., Froguel, P., Rettig, R., Mägi, R., Biffar, R., Schmidt, R., Middelberg, R.P., Carroll, R.J., Penninx, B.W., Scott, R.J., Katz, R., Sedaghat, S., Wild, S.H., Kardia, S.L., Ulivi, S., Hwang, S.J., Enroth, S., Kloiber, S., Trompet, S., Stengel, B., Hancock, S.J., Turner, S.T., Rosas, S.E., Stracke, S., Harris, T.B., Zeller, T., Zemunik, T., Lehtimäki, T., Illig, T., Aspelund, T., Nikopensius, T., Esko, T., Gyllensten, U., Völker, U., Emilsson, V., Vitart, V., Aalto, V., Gudnason, V., Chouraki, V., Chen, W.M., Igl, W., März, W., Koenig, W., Lieb, W., Loos, R.J., Liu, Y., Snieder, H., Pramstaller, P.P., Parsa, A., O'Connell, J.R., Susztak, K., Hamet, P., Tremblay, J., de Boer, I.H., Böger, C.A., Goessling, W., Chasman, D.I., Köttgen, A., Kao, W.H., and Fox, C.S.

Abstract

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

Published
2016

36. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Author

UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Pattaro, C., Teumer, A., Gorski, M., Chu, A.Y., Li, M., Mijatovic, V., Garnaas, M., Tin, A., Sorice, R., Li, Y., Taliun, D., Olden, M., Foster, M., Yang, Q., Chen, M.-H., Pers, T.H., Johnson, A.D., Ko, Y.-A., Fuchsberger, C., Tayo, B., Nalls, M., Feitosa, M.F., Isaacs, A., Dehghan, A., D'Adamo, P., Adeyemo, A., Dieffenbach, A.K., Zonderman, A.B., Nolte, I.M., Van Der Most, P.J., Wright, A.F., Shuldiner, A.R., Morrison, A.C., Hofman, A., Smith, A.V., Dreisbach, A.W., Franke, A., Uitterlinden, A.G., Metspalu, A., Tonjes, A., Lupo, A., Robino, A., Johansson, Å., Demirkan, A., Kollerits, B., Freedman, B.I., Ponte, B., Oostra, B.A., Paulweber, B., Krämer, B.K., Mitchell, B.D., Buckley, B.M., Peralta, C.A., Hayward, C., Helmer, C., Rotimi, C.N., Shaffer, C.M., Müller, C., Sala, C., Van Duijn, C.M., Saint-Pierre, A., Ackermann, D., Shriner, D., Ruggiero, D., Toniolo, D., Lu, Y., Cusi, D., Czamara, D., Ellinghaus, D., Siscovick, D.S., Ruderfer, D., Gieger, C., Grallert, H., Rochtchina, E., Atkinson, E.J., Holliday, E.G., Boerwinkle, E., Salvi, E., Bottinger, E.P., Murgia, F., Rivadeneira, F., Ernst, F., Kronenberg, F., Hu, F.B., Navis, G.J., Curhan, G.C., Ehret, G.B., Homuth, G., Coassin, S., Thun, G.-A., Pistis, G., Gambaro, G., Malerba, G., Montgomery, G.W., Eiriksdottir, G., Jacobs, G., Li, G., Wichmann, H.-E., Campbell, H., Schmidt, H., Wallaschofski, H., Völzke, H., Brenner, H., Kroemer, H.K., Kramer, H., Lin, H., Leach, I.M., Ford, I., Guessous, I., Rudan, I., Prokopenko, I., Borecki, I., Heid, I.M., Kolcic, I., Persico, I., Jukema, J.W., Wilson, J.F., Felix, J.F., Divers, J., Lambert, J.-C., Stafford, J.M., Gaspoz, J.-M., Smith, J.A., Faul, J.D., Wang, J.J., Ding, J., Hirschhorn, J.N., Attia, J., Whitfield, J.B., Chalmers, J., Viikari, J., Coresh, J., Denny, J.C., Karjalainen, J., Fernandes, J.K., Endlich, K., Butterbach, K., Keene, K.L., Lohman, K., Portas, L., Launer, L.J., Lyytikäinen, L.-P., Yengo, L., Franke, L., Ferrucci, L., Rose, L.M., Kedenko, L., Rao, M., Struchalin, M., Kleber, M.E., Cavalieri, M., Haun, M., Cornelis, M.C., Ciullo, M., Pirastu, M., De Andrade, M., McEvoy, M.A., Woodward, M., Adam, M., Cocca, M., Nauck, M., Imboden, M., Waldenberger, M., Pruijm, M., Metzger, M., Stumvoll, M., Evans, M.K., Sale, M.M., Kähönen, M., Boban, M., Bochud, M., Rheinberger, M., Verweij, N., Bouatia-Naji, N., Martin, N.G., Hastie, N., Probst-Hensch, N., Soranzo, N., Devuyst, O., Raitakari, O., Gottesman, O., Franco, O.H., Polasek, O., Gasparini, P., Munroe, P.B., Ridker, P.M., Mitchell, P., Muntner, P., Meisinger, C., Smit, J.H., Abecasis, G.R., Adair, L.S., Alexander, M., Altshuler, D., Amin, N., Arking, D.E., Arora, P., Aulchenko, Y., Bakker, S.J.L., Bandinelli, S., Barroso, I., Beckmann, J.S., Beilby, J.P., Bergman, R.N., Bergmann, S., Bis, J.C., Boehnke, M., Bonnycastle, L.L., Bornstein, S.R., Bots, M.L., Bragg-Gresham, J.L., Brand, S.-M., Brand, E., Braund, P.S., Brown, M.J., Burton, P.R., Casas, J.P., Caulfield, M.J., Chakravarti, A., Chambers, J.C., Chandak, G.R., Chang, Y.-P.C., Charchar, F.J., Chaturvedi, N., Cho, Y.S., Clarke, R., Collins, F.S., Collins, R., Connell, J.M., Cooper, J.A., Cooper, M.N., Cooper, R.S., Corsi, A.M., Dörr, M., Dahgam, S., Danesh, J., Smith, G.D., Day, I.N.M., Deloukas, P., Denniff, M., Dominiczak, A.F., Dong, Y., Doumatey, A., Elliott, P., Elosua, R., Erdmann, J., Eyheramendy, S., Farrall, M., Fava, C., Forrester, T., Fowkes, F.G.R., Fox, E.R., Frayling, T.M., Galan, P., Ganesh, S.K., Garcia, M., Gaunt, T.R., Glazer, N.L., Go, M.J., Goel, A., Grässler, J., Grobbee, D.E., Groop, L., Guarrera, S., Guo, X., Hadley, D., Hamsten, A., Han, B.-G., Hardy, R., Hartikainen, A.-L., Heath, S., Heckbert, S.R., Hedblad, B., Hercberg, S., Hernandez, D., Hicks, A.A., Hilton, G., Hingorani, A.D., Hoffman Bolton, J.A., Hopewell, J.C., Howard, P., Humphries, S.E., Hunt, S.C., Hveem, K., Ikram, M.A., Islam, M., Iwai, N., Jarvelin, M.-R., Jackson, A.U., Jafar, T.H., Janipalli, C.S., Johnson, T., Kathiresan, S., Khaw, K.-T., Kim, H.-L., Kinra, S., Kita, Y., Kivimaki, M., Kooner, J.S., Kumar, M.J.K., Kuh, D., Kulkarni, S.R., Kumari, M., Kuusisto, J., Kuznetsova, T., Laakso, M., Laan, M., Laitinen, J., Lakatta, E.G., Langefeld, C.D., Larson, M.G., Lathrop, M., Lawlor, D.A., Lawrence, R.W., Lee, J.-Y., Lee, N.R., Levy, D., Longstreth, W.T., Luan, J., Lucas, G., Ludwig, B., Mangino, M., Mani, K.R., Marmot, M.G., Mattace-Raso, F.U.S., Matullo, G., McArdle, W.L., McKenzie, C.A., Meitinger, T., Melander, O., Meneton, P., Meschia, J.F., Miki, T., Milaneschi, Y., Mohlke, K.L., Mooser, V., Morken, M.A., Morris, R.W., Mosley, T.H., Najjar, S., Narisu, N., Newton-Cheh, C., Nguyen, K.-D.H., Nilsson, P., Nyberg, F., O'Donnell, C.J., Ogihara, T., Ohkubo, T., Okamura, T., Ong, R.T.-H., Ongen, H., Onland-Moret, N.C., O'Reilly, P.F., Org, E., Orru, M., Palmas, W., Palmen, J., Palmer, L.J., Palmer, N.D., Parker, A.N., Peden, J.F., Peltonen, L., Perola, M., Pihur, V., Platou, C.G.P., Plump, A., Prabhakaran, D., Psaty, B.M., Raffel, L.J., Rao, D.C., Rasheed, A., Ricceri, F., Rice, K.M., Rosengren, A., Rotter, J.I., Rudock, M.E., Sõber, S., Salako, T., Saleheen, D., Salomaa, V., Samani, N.J., Schwartz, S.M., Schwarz, P.E.H., Scott, L.J., Scott, J., Scuteri, A., Sehmi, J.S., Seielstad, M., Seshadri, S., Sharma, P., Shaw-Hawkins, S., Shi, G., Shrine, N.R.G., Sijbrands, E.J.G., Sim, X., Singleton, A., Sjögren, M., Smith, N.L., Artigas, M.S., Spector, T.D., Staessen, J.A., Stancakova, A., Steinle, N.I., Strachan, D.P., Stringham, H.M., Sun, Y.V., Swift, A.J., Tabara, Y., Tai, E.-S., Talmud, P.J., Taylor, A., Terzic, J., Thelle, D.S., Tobin, M.D., Tomaszewski, M., Tripathy, V., Tuomilehto, J., Tzoulaki, I., Uda, M., Ueshima, H., Uiterwaal, C.S.P.M., Umemura, S., Van Der Harst, P., Van Der Schouw, Y.T., Van Gilst, W.H., Vartiainen, E., Vasan, R.S., Veldre, G., Verwoert, G.C., Viigimaa, M., Vinay, D.G., Vineis, P., Voight, B.F., Vollenweider, P., Wagenknecht, L.E., Wain, L.V., Wang, X., Wang, T.J., Wareham, N.J., Watkins, H., Weder, A.B., Whincup, P.H., Wiggins, K.L., Witteman, J.C.M., Wong, A., Wu, Y., Yajnik, C.S., Yao, J., Young, J.H., Zelenika, D., Zhai, G., Zhang, W., Zhang, F., Zhao, J.H., Zhu, H., Zhu, X., Zitting, P., Zukowska-Szczechowska, E., Okada, Y., Wu, J.-Y., Gu, D., Takeuchi, F., Takahashi, A., Maeda, S., Tsunoda, T., Chen, P., Lim, S.-C., Wong, T.-Y., Liu, J., Young, T.L., Aung, T., Teo, Y.-Y., Kim, Y.J., Kang, D., Chen, C.-H., Tsai, F.-J., Chang, L.-C., Fann, S.-J.C., Mei, H., Hixson, J.E., Chen, S., Katsuya, T., Isono, M., Albrecht, E., Yamamoto, K., Kubo, M., Nakamura, Y., Kamatani, N., Kato, N., He, J., Chen, Y.-T., Tanaka, T., Reilly, M.P., Schunkert, H., Assimes, T.L., Hall, A., Hengstenberg, C., König, I.R., Laaksonen, R., McPherson, R., Thompson, J.R., Thorsteinsdottir, U., Ziegler, A., Absher, D., Chen, L., Cupples, L.A., Halperin, E., Musunuru, K., Preuss, M., Schillert, A., Thorleifsson, G., Wells, G.A., Holm, H., Roberts, R., Stewart, A.F.R., Fortmann, S., Go, A., Hlatky, M., Iribarren, C., Knowles, J., Myers, R., Quertermous, T., Sidney, S., Risch, N., Tang, H., Blankenberg, S., Schnabel, R., Sinning, C., Lackner, K.J., Tiret, L., Nicaud, V., Cambien, F., Bickel, C., Rupprecht, H.J., Perret, C., Proust, C., Münzel, T.F., Barbalic, M., Chen, I.Y.-D., Demissie-Banjaw, S., Folsom, A., Lumley, T., Marciante, K., Taylor, K.D., Volcik, K., Gretarsdottir, S., Gulcher, J.R., Kong, A., Stefansson, K., Thorgeirsson, G., Andersen, K., Fischer, M., Grosshennig, A., Linsel-Nitschke, P., Stark, K., Schreiber, S., Aherrahrou, Z., Bruse, P., Doering, A., Klopp, N., Diemert, P., Loley, C., Medack, A., Nahrstedt, J., Peters, A., Wagner, A.K., Willenborg, C., Böhm, B.O., Dobnig, H., Grammer, T.B., Hoffmann, M.M., Meinitzer, A., Winkelmann, B.R., Pilz, S., Renner, W., Scharnagl, H., Stojakovic, T., Tomaschitz, A., Winkler, K., Guiducci, C., Burtt, N., Gabriel, S.B., Dandona, S., Jarinova, O., Qu, L., Wilensky, R., Matthai, W., Hakonarson, H.H., Devaney, J., Burnett, M.S., Pichard, A.D., Kent, K.M., Satler, L., Lindsay, J.M., Waksman, R., Knouff, C.W., Waterworth, D.M., Walker, M.C., Epstein, S.E., Rader, D.J., Nelson, C.P., Wright, B.J., Balmforth, A.J., Ball, S.G., Loehr, L.R., Rosamond, W.D., Benjamin, E., Haritunians, T., Couper, D., Murabito, J., Wang, Y.A., Stricker, B.H., Chang, P.P., Willerson, J.T., Felix, S.B., Watzinger, N., Aragam, J., Zweiker, R., Lind, L., Rodeheffer, R.J., Greiser, K.H., Deckers, J.W., Stritzke, J., Ingelsson, E., Kullo, I., Haerting, J., Reffelmann, T., Redfield, M.M., Werdan, K., Mitchell, G.F., Arnett, D.K., Gottdiener, J.S., Blettner, M., Friedrich, N., Kovacs, P., Wild, P.S., Froguel, P., Rettig, R., Mägi, R., Biffar, R., Schmidt, R., Middelberg, R.P.S., Carroll, R.J., Penninx, B.W., Scott, R.J., Katz, R., Sedaghat, S., Wild, S.H., Kardia, S.L.R., Ulivi, S., Hwang, S.-J., Enroth, S., Kloiber, S., Trompet, S., Stengel, B., Hancock, S.J., Turner, S.T., Rosas, S.E., Stracke, S., Harris, T.B., Zeller, T., Zemunik, T., Lehtimäki, T., Illig, T., Aspelund, T., Nikopensius, T., Esko, T., Gyllensten, U., Völker, U., Emilsson, V., Vitart, V., Aalto, V., Gudnason, V., Chouraki, V., Chen, W.-M., Igl, W., März, W., Koenig, W., Lieb, W., Loos, R.J.F., Liu, Y., Snieder, H., Pramstaller, P.P., Parsa, A., O'Connell, J.R., Susztak, K., Hamet, P., Tremblay, J., De Boer, I.H., Böger, C.A., Goessling, W., Chasman, D.I., Köttgen, A., Kao, W.H.L., Fox, C.S., UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Pattaro, C., Teumer, A., Gorski, M., Chu, A.Y., Li, M., Mijatovic, V., Garnaas, M., Tin, A., Sorice, R., Li, Y., Taliun, D., Olden, M., Foster, M., Yang, Q., Chen, M.-H., Pers, T.H., Johnson, A.D., Ko, Y.-A., Fuchsberger, C., Tayo, B., Nalls, M., Feitosa, M.F., Isaacs, A., Dehghan, A., D'Adamo, P., Adeyemo, A., Dieffenbach, A.K., Zonderman, A.B., Nolte, I.M., Van Der Most, P.J., Wright, A.F., Shuldiner, A.R., Morrison, A.C., Hofman, A., Smith, A.V., Dreisbach, A.W., Franke, A., Uitterlinden, A.G., Metspalu, A., Tonjes, A., Lupo, A., Robino, A., Johansson, Å., Demirkan, A., Kollerits, B., Freedman, B.I., Ponte, B., Oostra, B.A., Paulweber, B., Krämer, B.K., Mitchell, B.D., Buckley, B.M., Peralta, C.A., Hayward, C., Helmer, C., Rotimi, C.N., Shaffer, C.M., Müller, C., Sala, C., Van Duijn, C.M., Saint-Pierre, A., Ackermann, D., Shriner, D., Ruggiero, D., Toniolo, D., Lu, Y., Cusi, D., Czamara, D., Ellinghaus, D., Siscovick, D.S., Ruderfer, D., Gieger, C., Grallert, H., Rochtchina, E., Atkinson, E.J., Holliday, E.G., Boerwinkle, E., Salvi, E., Bottinger, E.P., Murgia, F., Rivadeneira, F., Ernst, F., Kronenberg, F., Hu, F.B., Navis, G.J., Curhan, G.C., Ehret, G.B., Homuth, G., Coassin, S., Thun, G.-A., Pistis, G., Gambaro, G., Malerba, G., Montgomery, G.W., Eiriksdottir, G., Jacobs, G., Li, G., Wichmann, H.-E., Campbell, H., Schmidt, H., Wallaschofski, H., Völzke, H., Brenner, H., Kroemer, H.K., Kramer, H., Lin, H., Leach, I.M., Ford, I., Guessous, I., Rudan, I., Prokopenko, I., Borecki, I., Heid, I.M., Kolcic, I., Persico, I., Jukema, J.W., Wilson, J.F., Felix, J.F., Divers, J., Lambert, J.-C., Stafford, J.M., Gaspoz, J.-M., Smith, J.A., Faul, J.D., Wang, J.J., Ding, J., Hirschhorn, J.N., Attia, J., Whitfield, J.B., Chalmers, J., Viikari, J., Coresh, J., Denny, J.C., Karjalainen, J., Fernandes, J.K., Endlich, K., Butterbach, K., Keene, K.L., Lohman, K., Portas, L., Launer, L.J., Lyytikäinen, L.-P., Yengo, L., Franke, L., Ferrucci, L., Rose, L.M., Kedenko, L., Rao, M., Struchalin, M., Kleber, M.E., Cavalieri, M., Haun, M., Cornelis, M.C., Ciullo, M., Pirastu, M., De Andrade, M., McEvoy, M.A., Woodward, M., Adam, M., Cocca, M., Nauck, M., Imboden, M., Waldenberger, M., Pruijm, M., Metzger, M., Stumvoll, M., Evans, M.K., Sale, M.M., Kähönen, M., Boban, M., Bochud, M., Rheinberger, M., Verweij, N., Bouatia-Naji, N., Martin, N.G., Hastie, N., Probst-Hensch, N., Soranzo, N., Devuyst, O., Raitakari, O., Gottesman, O., Franco, O.H., Polasek, O., Gasparini, P., Munroe, P.B., Ridker, P.M., Mitchell, P., Muntner, P., Meisinger, C., Smit, J.H., Abecasis, G.R., Adair, L.S., Alexander, M., Altshuler, D., Amin, N., Arking, D.E., Arora, P., Aulchenko, Y., Bakker, S.J.L., Bandinelli, S., Barroso, I., Beckmann, J.S., Beilby, J.P., Bergman, R.N., Bergmann, S., Bis, J.C., Boehnke, M., Bonnycastle, L.L., Bornstein, S.R., Bots, M.L., Bragg-Gresham, J.L., Brand, S.-M., Brand, E., Braund, P.S., Brown, M.J., Burton, P.R., Casas, J.P., Caulfield, M.J., Chakravarti, A., Chambers, J.C., Chandak, G.R., Chang, Y.-P.C., Charchar, F.J., Chaturvedi, N., Cho, Y.S., Clarke, R., Collins, F.S., Collins, R., Connell, J.M., Cooper, J.A., Cooper, M.N., Cooper, R.S., Corsi, A.M., Dörr, M., Dahgam, S., Danesh, J., Smith, G.D., Day, I.N.M., Deloukas, P., Denniff, M., Dominiczak, A.F., Dong, Y., Doumatey, A., Elliott, P., Elosua, R., Erdmann, J., Eyheramendy, S., Farrall, M., Fava, C., Forrester, T., Fowkes, F.G.R., Fox, E.R., Frayling, T.M., Galan, P., Ganesh, S.K., Garcia, M., Gaunt, T.R., Glazer, N.L., Go, M.J., Goel, A., Grässler, J., Grobbee, D.E., Groop, L., Guarrera, S., Guo, X., Hadley, D., Hamsten, A., Han, B.-G., Hardy, R., Hartikainen, A.-L., Heath, S., Heckbert, S.R., Hedblad, B., Hercberg, S., Hernandez, D., Hicks, A.A., Hilton, G., Hingorani, A.D., Hoffman Bolton, J.A., Hopewell, J.C., Howard, P., Humphries, S.E., Hunt, S.C., Hveem, K., Ikram, M.A., Islam, M., Iwai, N., Jarvelin, M.-R., Jackson, A.U., Jafar, T.H., Janipalli, C.S., Johnson, T., Kathiresan, S., Khaw, K.-T., Kim, H.-L., Kinra, S., Kita, Y., Kivimaki, M., Kooner, J.S., Kumar, M.J.K., Kuh, D., Kulkarni, S.R., Kumari, M., Kuusisto, J., Kuznetsova, T., Laakso, M., Laan, M., Laitinen, J., Lakatta, E.G., Langefeld, C.D., Larson, M.G., Lathrop, M., Lawlor, D.A., Lawrence, R.W., Lee, J.-Y., Lee, N.R., Levy, D., Longstreth, W.T., Luan, J., Lucas, G., Ludwig, B., Mangino, M., Mani, K.R., Marmot, M.G., Mattace-Raso, F.U.S., Matullo, G., McArdle, W.L., McKenzie, C.A., Meitinger, T., Melander, O., Meneton, P., Meschia, J.F., Miki, T., Milaneschi, Y., Mohlke, K.L., Mooser, V., Morken, M.A., Morris, R.W., Mosley, T.H., Najjar, S., Narisu, N., Newton-Cheh, C., Nguyen, K.-D.H., Nilsson, P., Nyberg, F., O'Donnell, C.J., Ogihara, T., Ohkubo, T., Okamura, T., Ong, R.T.-H., Ongen, H., Onland-Moret, N.C., O'Reilly, P.F., Org, E., Orru, M., Palmas, W., Palmen, J., Palmer, L.J., Palmer, N.D., Parker, A.N., Peden, J.F., Peltonen, L., Perola, M., Pihur, V., Platou, C.G.P., Plump, A., Prabhakaran, D., Psaty, B.M., Raffel, L.J., Rao, D.C., Rasheed, A., Ricceri, F., Rice, K.M., Rosengren, A., Rotter, J.I., Rudock, M.E., Sõber, S., Salako, T., Saleheen, D., Salomaa, V., Samani, N.J., Schwartz, S.M., Schwarz, P.E.H., Scott, L.J., Scott, J., Scuteri, A., Sehmi, J.S., Seielstad, M., Seshadri, S., Sharma, P., Shaw-Hawkins, S., Shi, G., Shrine, N.R.G., Sijbrands, E.J.G., Sim, X., Singleton, A., Sjögren, M., Smith, N.L., Artigas, M.S., Spector, T.D., Staessen, J.A., Stancakova, A., Steinle, N.I., Strachan, D.P., Stringham, H.M., Sun, Y.V., Swift, A.J., Tabara, Y., Tai, E.-S., Talmud, P.J., Taylor, A., Terzic, J., Thelle, D.S., Tobin, M.D., Tomaszewski, M., Tripathy, V., Tuomilehto, J., Tzoulaki, I., Uda, M., Ueshima, H., Uiterwaal, C.S.P.M., Umemura, S., Van Der Harst, P., Van Der Schouw, Y.T., Van Gilst, W.H., Vartiainen, E., Vasan, R.S., Veldre, G., Verwoert, G.C., Viigimaa, M., Vinay, D.G., Vineis, P., Voight, B.F., Vollenweider, P., Wagenknecht, L.E., Wain, L.V., Wang, X., Wang, T.J., Wareham, N.J., Watkins, H., Weder, A.B., Whincup, P.H., Wiggins, K.L., Witteman, J.C.M., Wong, A., Wu, Y., Yajnik, C.S., Yao, J., Young, J.H., Zelenika, D., Zhai, G., Zhang, W., Zhang, F., Zhao, J.H., Zhu, H., Zhu, X., Zitting, P., Zukowska-Szczechowska, E., Okada, Y., Wu, J.-Y., Gu, D., Takeuchi, F., Takahashi, A., Maeda, S., Tsunoda, T., Chen, P., Lim, S.-C., Wong, T.-Y., Liu, J., Young, T.L., Aung, T., Teo, Y.-Y., Kim, Y.J., Kang, D., Chen, C.-H., Tsai, F.-J., Chang, L.-C., Fann, S.-J.C., Mei, H., Hixson, J.E., Chen, S., Katsuya, T., Isono, M., Albrecht, E., Yamamoto, K., Kubo, M., Nakamura, Y., Kamatani, N., Kato, N., He, J., Chen, Y.-T., Tanaka, T., Reilly, M.P., Schunkert, H., Assimes, T.L., Hall, A., Hengstenberg, C., König, I.R., Laaksonen, R., McPherson, R., Thompson, J.R., Thorsteinsdottir, U., Ziegler, A., Absher, D., Chen, L., Cupples, L.A., Halperin, E., Musunuru, K., Preuss, M., Schillert, A., Thorleifsson, G., Wells, G.A., Holm, H., Roberts, R., Stewart, A.F.R., Fortmann, S., Go, A., Hlatky, M., Iribarren, C., Knowles, J., Myers, R., Quertermous, T., Sidney, S., Risch, N., Tang, H., Blankenberg, S., Schnabel, R., Sinning, C., Lackner, K.J., Tiret, L., Nicaud, V., Cambien, F., Bickel, C., Rupprecht, H.J., Perret, C., Proust, C., Münzel, T.F., Barbalic, M., Chen, I.Y.-D., Demissie-Banjaw, S., Folsom, A., Lumley, T., Marciante, K., Taylor, K.D., Volcik, K., Gretarsdottir, S., Gulcher, J.R., Kong, A., Stefansson, K., Thorgeirsson, G., Andersen, K., Fischer, M., Grosshennig, A., Linsel-Nitschke, P., Stark, K., Schreiber, S., Aherrahrou, Z., Bruse, P., Doering, A., Klopp, N., Diemert, P., Loley, C., Medack, A., Nahrstedt, J., Peters, A., Wagner, A.K., Willenborg, C., Böhm, B.O., Dobnig, H., Grammer, T.B., Hoffmann, M.M., Meinitzer, A., Winkelmann, B.R., Pilz, S., Renner, W., Scharnagl, H., Stojakovic, T., Tomaschitz, A., Winkler, K., Guiducci, C., Burtt, N., Gabriel, S.B., Dandona, S., Jarinova, O., Qu, L., Wilensky, R., Matthai, W., Hakonarson, H.H., Devaney, J., Burnett, M.S., Pichard, A.D., Kent, K.M., Satler, L., Lindsay, J.M., Waksman, R., Knouff, C.W., Waterworth, D.M., Walker, M.C., Epstein, S.E., Rader, D.J., Nelson, C.P., Wright, B.J., Balmforth, A.J., Ball, S.G., Loehr, L.R., Rosamond, W.D., Benjamin, E., Haritunians, T., Couper, D., Murabito, J., Wang, Y.A., Stricker, B.H., Chang, P.P., Willerson, J.T., Felix, S.B., Watzinger, N., Aragam, J., Zweiker, R., Lind, L., Rodeheffer, R.J., Greiser, K.H., Deckers, J.W., Stritzke, J., Ingelsson, E., Kullo, I., Haerting, J., Reffelmann, T., Redfield, M.M., Werdan, K., Mitchell, G.F., Arnett, D.K., Gottdiener, J.S., Blettner, M., Friedrich, N., Kovacs, P., Wild, P.S., Froguel, P., Rettig, R., Mägi, R., Biffar, R., Schmidt, R., Middelberg, R.P.S., Carroll, R.J., Penninx, B.W., Scott, R.J., Katz, R., Sedaghat, S., Wild, S.H., Kardia, S.L.R., Ulivi, S., Hwang, S.-J., Enroth, S., Kloiber, S., Trompet, S., Stengel, B., Hancock, S.J., Turner, S.T., Rosas, S.E., Stracke, S., Harris, T.B., Zeller, T., Zemunik, T., Lehtimäki, T., Illig, T., Aspelund, T., Nikopensius, T., Esko, T., Gyllensten, U., Völker, U., Emilsson, V., Vitart, V., Aalto, V., Gudnason, V., Chouraki, V., Chen, W.-M., Igl, W., März, W., Koenig, W., Lieb, W., Loos, R.J.F., Liu, Y., Snieder, H., Pramstaller, P.P., Parsa, A., O'Connell, J.R., Susztak, K., Hamet, P., Tremblay, J., De Boer, I.H., Böger, C.A., Goessling, W., Chasman, D.I., Köttgen, A., Kao, W.H.L., and Fox, C.S.

Abstract

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways. © 2016, Nature Publishing Group. All rights reserved.

Published
2016

37. Plasma acylcarnitines and risk of cardiovascular disease: Effect of Mediterranean diet interventions

Author

Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Guasch-Ferré M., Zheng Y., Ruiz-Canela M., Hruby A., Martínez-González M.A., Clish C.B., Corella D., Estruch R., Ros E., Fitó M., Dennis C., Morales-Gil I.M., Arós F., Fiol M., Lapetra J., Serra-Majem L., Hu F.B., Salas-Salvadó J., Bioquímica i Biotecnologia, Universitat Rovira i Virgili, and Guasch-Ferré M., Zheng Y., Ruiz-Canela M., Hruby A., Martínez-González M.A., Clish C.B., Corella D., Estruch R., Ros E., Fitó M., Dennis C., Morales-Gil I.M., Arós F., Fiol M., Lapetra J., Serra-Majem L., Hu F.B., Salas-Salvadó J.

Abstract

Previous studies have suggested that metabolite profiles of elevated acylcarnitines were associated with increased risk of cardiovascular disease (CVD) in populations with established coronary disease. However, to our knowledge, this association has not been evaluated in the context of primary cardiovascular prevention.We evaluated the association between 28 plasma acylcarnitine species and risk of incident CVD and the potential modifying effect of Mediterranean diet (MedDiet) interventions.We measured plasma acylcarnitines with the use of high-throughput liquid chromatography-tandem mass spectrometry at baseline and after 1 y of follow-up, both individually and classified into short-, medium-, or long-chain scores, in a case-cohort study within the Prevención con Dieta Mediterránea (PREDIMED) study, which is a randomized Mediterranean dietary intervention for primary cardiovascular prevention. A randomly selected subcohort (n = 751) and all available incident CVD cases (n = 229) after 4.8 y of follow-up were included in the current study.After adjustment for age, sex, body mass index, and other CVD risk factors, participants in the highest quartile of baseline short- and medium-chain acylcarnitines had a higher risk of CVD than did participants in the lowest quartile [HRs: 1.80 (95% CI: 1.11, 2.91; P-trend 0.01) and 1.55 (95% CI: 1.01, 2.48; P-trend = 0.04), respectively]. Increased short-chain acylcarnitines after 1 y were associated with higher risks of total CVD and stroke. Participants with higher baseline concentrations of short-, medium-, and long-chain acylcarnitines who were randomly assigned to the control group had a higher risk of CVD than did subjects with lower concentrations of acylcarnitines who were assigned to the MedDiet group.Our data support the con

Published
2016

38. Dietary patterns during high school and risk of colorectal adenoma in a cohort of middle-aged women

Author

Nimptsch, K., Malik, V.S., Fung, T.T., Pischon, T., Hu, F.B., Willett, W.C., Fuchs, C.S., Ogino, S., Chan, A.T., Giovannucci, E., and Wu, K.

Subjects
Cardiovascular and Metabolic Diseases
Abstract

Adolescent diet may be etiologically relevant for later risk of colorectal adenoma, a precursor of colorectal cancer. We aimed to examine associations between adolescent dietary patterns (derived using factor analysis) and risk of colorectal adenoma in middle adulthood. We analyzed data from 17,221 women participating in the Nurses' Health Study II, who had completed a validated high school (HS) food frequency questionnaire in 1998 when they were 34-51 years old, and had subsequently undergone at least one lower bowel endoscopy. Between 1998 and 2007, 1,299 women were diagnosed with at least one colorectal adenoma. In multivariable models adjusted for adult dietary patterns, a higher "prudent" pattern during HS, characterized by high consumption of vegetables, fruit and fish was associated with a statistically significantly lower risk of rectal (odds ratio [OR] highest vs. lowest quintile, 0.45, 95% CI 0.27-0.75, p-trend=0.005), but not colon adenomas. A higher "Western" pattern during HS, characterized by high consumption of desserts and sweets, snack foods and red and processed meat, was significantly associated with rectal (OR 1.78, 95% CI 1.12-2.85, p-trend=0.005) and advanced (OR 1.58, 95% CI 1.07-2.33, p-trend=0.08), but not associated with colon or non-advanced adenomas. This study suggests that overall eating patterns during high school may influence later risk of rectal and advanced adenoma, independent of adult diet. Our results support the hypothesis that diet during early life may influence colorectal carcinogenesis.

Published
2014

39. Olive oil intake and risk of cardiovascular disease and mortality in the PREDIMED Study

Author

Salas-Salvadó, J., Martínez, J.A., Ruiz-Gutiérrez, V., Sorlí, J.V., Buil-Cosiales, P., Basora, J., Lamuela-Raventós, R.M., Pintó, X., Muñoz, M.A., Serra-Majem, L., Fiol, M. , Lapetra, J., Gómez-Gracia, E., Recondo, J., Corella, D., Ros, E., Estruch, R., Bulló, M., Fitó, M., Martínez-González, M.A., Hu, F.B., Guasch-Ferré, M., Bioquímica i Biotecnologia, and Universitat Rovira i Virgili.

Subjects
Sistema cardiovascular--Malalties
Abstract

Background: It is unknown whether individuals at high cardiovascular risk sustain a benefit in cardiovascular disease from increased olive oil consumption. The aim was to assess the association between total olive oil intake, its varieties (extra virgin and common olive oil) and the risk of cardiovascular disease and mortality in a Mediterranean population at high cardiovascular risk. Methods: We included 7,216 men and women at high cardiovascular risk, aged 55 to 80 years, from the PREvención con DIeta MEDiterránea (PREDIMED) study, a multicenter, randomized, controlled, clinical trial. Participants were randomized to one of three interventions: Mediterranean Diets supplemented with nuts or extra-virgin olive oil, or a control low-fat diet. The present analysis was conducted as an observational prospective cohort study. The median follow-up was 4.8 years. Cardiovascular disease (stroke, myocardial infarction and cardiovascular death) and mortality were ascertained by medical records and National Death Index. Olive oil consumption was evaluated with validated food frequency questionnaires. Multivariate Cox proportional hazards and generalized estimating equations were used to assess the association between baseline and yearly repeated measurements of olive oil intake, cardiovascular disease and mortality. Results: During follow-up, 277 cardiovascular events and 323 deaths occurred. Participants in the highest energy-adjusted tertile of baseline total olive oil and extra-virgin olive oil consumption had 35% (HR: 0.65; 95% CI: 0.47 to 0.89) and 39% (HR: 0.61; 95% CI: 0.44 to 0.85) cardiovascular disease risk reduction, respectively, compared to the reference. Higher baseline total olive oil consumption was associated with 48% (HR: 0.52; 95% CI: 0.29 to 0.93) reduced risk

Published
2014

40. Impact of the adipokine adiponectin and the hepatokine fetuin-A on the development of type 2 diabetes: prospective cohort- and cross-sectional phenotyping studies

Author

Stefan, N., Sun, Q., Fritsche, A., Machann, J., Schick, F., Gerst, F., Jeppesen, C., Joost, H.G., Hu, F.B., Boeing, H., Ullrich, S., Häring, H.-U., and Schulze, M.B.

Subjects
Adult, Male, Risk, alpha-2-HS-Glycoprotein, Physiology, Epidemiology, lcsh:Medicine, Nonalcoholic Steatohepatitis, Gastroenterology and Hepatology, Biochemistry, Body Mass Index, Endocrinology, Glucose Intolerance, Medicine and Health Sciences, Diabetes Mellitus, Humans, Insulin, Prospective Studies, Obesity, lcsh:Science, Cardiovascular Disease Epidemiology, Aged, Nutrition, Diabetic Endocrinology, Endocrine Physiology, Liver Diseases, Body Weight, lcsh:R, Biology and Life Sciences, Middle Aged, Hormones, Type 2 Diabetes, Biomarker Epidemiology, Cross-Sectional Studies, Phenotype, Diabetes Mellitus, Type 2, Physiological Parameters, Metabolic Disorders, Multivariate Analysis, Female, lcsh:Q, Adiponectin, Insulin Resistance, Waist Circumference, Biomarkers, Research Article
Abstract

BACKGROUND: Among adipokines and hepatokines, adiponectin and fetuin-A were consistently found to predict the incidence of type 2 diabetes, both by regulating insulin sensitivity. OBJECTIVE: To determine to what extent circulating adiponectin and fetuin-A are independently associated with incident type 2 diabetes in humans, and the major mechanisms involved. METHODS: Relationships with incident diabetes were tested in two cohort studies: within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study (628 cases) and the Nurses' Health Study (NHS; 470 cases). Relationships with body fat compartments, insulin sensitivity and insulin secretion were studied in the Tübingen Lifestyle Intervention Program (TULIP; N = 358). RESULTS: Circulating adiponectin and fetuin-A, independently of several confounders and of each other, associated with risk of diabetes in EPIC-Potsdam (RR for 1 SD: adiponectin: 0.45 [95% CI 0.37-0.54], fetuin-A: 1.18 [1.05-1.32]) and the NHS (0.51 [0.42-0.62], 1.35 [1.16-1.58]). Obesity measures considerably attenuated the association of adiponectin, but not of fetuin-A. Subjects with low adiponectin and concomitantly high fetuin-A had the highest risk. Whereas both proteins were independently (both p

Published
2014

41. Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

Author

Cornelis, M.C., Byrne, E.M., Esko, T., Nalls, M.A., Ganna, A., Paynter, N., Monda, K.L., Amin, N., Fischer, K., Renstrom, F., Ngwa, J.S., Huikari, V., Cavadino, A., Nolte, I.M., Teumer, A., Yu, K., Marques-Vidal, P., Rawal, R., Manichaikul, A., Wojczynski, M.K., Vink, J.M., Zhao, J.H., Burlutsky, G., Lahti, J., Mikkila, V., Lemaitre, R.N., Eriksson, J., Musani, S.K., Tanaka, T., Geller, F., Luan, J., Hui, J., Magi, R., Dimitriou, M., Garcia, M.E., Ho, W.K., Wright, M.J., Rose, L.M., Magnusson, P.K.E., Pedersen, N.L., Couper, D., Oostra, B.A., Hofman, A., Ikram, M.A., Tiemeier, H.W., Uitterlinden, A.G., Rooij, F.J. van, Barroso, I., Johansson, I., Xue, L., Kaakinen, M., Milani, L., Power, C., Snieder, H., Stolk, R.P., Baumeister, S.E., Biffar, R., Gu, F., Bastardot, F., Kutalik, Z., Jacobs, D.R., Jr., Forouhi, N.G., Mihailov, E., Lind, L., Lindgren, C., Michaelsson, K., Morris, A., Jensen, M., Khaw, K.T., Luben, R.N., Wang, J.J., Mannisto, S., Perala, M.M., Kahonen, M., Lehtimaki, T., Viikari, J., Mozaffarian, D., Mukamal, K., Psaty, B.M., Doring, A., Heath, A.C., Montgomery, G.W., Dahmen, N., Carithers, T., Tucker, K.L., Ferrucci, L., Boyd, H.A., Melbye, M., Treur, J.L., Mellstrom, D., Hottenga, J.J., Prokopenko, I., Tonjes, A., Deloukas, P., Kanoni, S., Lorentzon, M., Houston, D.K., Liu, Y., Danesh, J., Rasheed, A., Mason, M.A., Zonderman, A.B., Franke, L., Kristal, B.S., Karjalainen, J., Reed, D.R., Westra, H.J., Evans, M.K., Saleheen, D., Harris, T.B., Dedoussis, G., Curhan, G.C., Stumvoll, M., Beilby, J., Pasquale, L.R., Feenstra, B., Bandinelli, S., Ordovas, J.M., Chan, A.T., Peters, U., Ohlsson, C., Gieger, C., Martin, N.G., Waldenberger, M., Siscovick, D.S., Raitakari, O., Eriksson, J.G., Mitchell, P., Hunter, D.J., Kraft, P., Rimm, E.B., Boomsma, D.I., Borecki, I.B., Loos, R.J.F., Wareham, N.J., Vollenweider, P., Caporaso, N., Grabe, H.J., Neuhouser, M.L., Wolffenbuttel, B.H.R., Hu, F.B., Hypponen, E., Jarvelin, M.R., Cupples, L.A., Franks, P.W., Ridker, P.M., Duijn, C.M. van, Heiss, G., Metspalu, A., North, K.E., Ingelsson, E., Nettleton, J.A., Dam, R.M. van, Chasman, D.I., Cornelis, M.C., Byrne, E.M., Esko, T., Nalls, M.A., Ganna, A., Paynter, N., Monda, K.L., Amin, N., Fischer, K., Renstrom, F., Ngwa, J.S., Huikari, V., Cavadino, A., Nolte, I.M., Teumer, A., Yu, K., Marques-Vidal, P., Rawal, R., Manichaikul, A., Wojczynski, M.K., Vink, J.M., Zhao, J.H., Burlutsky, G., Lahti, J., Mikkila, V., Lemaitre, R.N., Eriksson, J., Musani, S.K., Tanaka, T., Geller, F., Luan, J., Hui, J., Magi, R., Dimitriou, M., Garcia, M.E., Ho, W.K., Wright, M.J., Rose, L.M., Magnusson, P.K.E., Pedersen, N.L., Couper, D., Oostra, B.A., Hofman, A., Ikram, M.A., Tiemeier, H.W., Uitterlinden, A.G., Rooij, F.J. van, Barroso, I., Johansson, I., Xue, L., Kaakinen, M., Milani, L., Power, C., Snieder, H., Stolk, R.P., Baumeister, S.E., Biffar, R., Gu, F., Bastardot, F., Kutalik, Z., Jacobs, D.R., Jr., Forouhi, N.G., Mihailov, E., Lind, L., Lindgren, C., Michaelsson, K., Morris, A., Jensen, M., Khaw, K.T., Luben, R.N., Wang, J.J., Mannisto, S., Perala, M.M., Kahonen, M., Lehtimaki, T., Viikari, J., Mozaffarian, D., Mukamal, K., Psaty, B.M., Doring, A., Heath, A.C., Montgomery, G.W., Dahmen, N., Carithers, T., Tucker, K.L., Ferrucci, L., Boyd, H.A., Melbye, M., Treur, J.L., Mellstrom, D., Hottenga, J.J., Prokopenko, I., Tonjes, A., Deloukas, P., Kanoni, S., Lorentzon, M., Houston, D.K., Liu, Y., Danesh, J., Rasheed, A., Mason, M.A., Zonderman, A.B., Franke, L., Kristal, B.S., Karjalainen, J., Reed, D.R., Westra, H.J., Evans, M.K., Saleheen, D., Harris, T.B., Dedoussis, G., Curhan, G.C., Stumvoll, M., Beilby, J., Pasquale, L.R., Feenstra, B., Bandinelli, S., Ordovas, J.M., Chan, A.T., Peters, U., Ohlsson, C., Gieger, C., Martin, N.G., Waldenberger, M., Siscovick, D.S., Raitakari, O., Eriksson, J.G., Mitchell, P., Hunter, D.J., Kraft, P., Rimm, E.B., Boomsma, D.I., Borecki, I.B., Loos, R.J.F., Wareham, N.J., Vollenweider, P., Caporaso, N., Grabe, H.J., Neuhouser, M.L., Wolffenbuttel, B.H.R., Hu, F.B., Hypponen, E., Jarvelin, M.R., Cupples, L.A., Franks, P.W., Ridker, P.M., Duijn, C.M. van, Heiss, G., Metspalu, A., North, K.E., Ingelsson, E., Nettleton, J.A., Dam, R.M. van, and Chasman, D.I.

Abstract

Item does not contain fulltext, 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 x 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.

Published
2015

42. Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

Author

The, Coffee, Cornelis, M.C., Byrne, E.M., Esko, T., Nalls, M.A., Ganna, A., Paynter, N., Monda, K.L., Amin, N., Fischer, K., Renstrom, F., Ngwa, J.S., Huikari, V., Cavadino, A., Nolte, I.M., Teumer, A., Yu, K., Marques-Vidal, P., Rawal, R., Manichaikul, A., Wojczynski, M.K., Vink, J.M., Zhao, J.H., Burlutsky, G., Lahti, J., Mikkilä, V., Lemaitre, R.N., Eriksson, J., Musani, S.K., Tanaka, T., Geller, F., Luan, J., Hui, J., Mägi, R., Dimitriou, M., Garcia, M.E., Ho, W.K., Wright, M.J., Rose, L.M., Magnusson, P.K., Pedersen, N.L., Couper, D., Oostra, B.A., Hofman, A., Ikram, M.A., Tiemeier, H.W., Uitterlinden, A.G., van Rooij, F.J., Barroso, I., Johansson, I., Xue, L., Kaakinen, M., Milani, L., Power, C., Snieder, H., Stolk, R.P., Baumeister, S.E., Biffar, R., Gu, F., Bastardot, F., Kutalik, Z., Jacobs, D.R., Forouhi, N.G., Mihailov, E., Lind, L., Lindgren, C., Michaëlsson, K., Morris, A., Jensen, M., Khaw, K.T., Luben, R.N., Wang, J.J., Männistö, S., Perälä, M.M., Kähönen, M., Lehtimäki, T., Viikari, J., Mozaffarian, D., Mukamal, K., Psaty, B.M., Döring, A., Heath, A.C., Montgomery, G.W., Dahmen, N., Carithers, T., Tucker, K.L., Ferrucci, L., Boyd, H.A., Melbye, M., Treur, J.L., Mellström, D., Hottenga, J.J., Prokopenko, I., Tönjes, A., Deloukas, P., Kanoni, S., Lorentzon, M., Houston, D.K., Liu, Y., Danesh, J., Rasheed, A., Mason, M.A., Zonderman, A.B., Franke, L., Kristal, B.S., Karjalainen, J., Reed, D.R., Westra, H.J., Evans, M.K., Saleheen, D., Harris, T.B., Dedoussis, G., Curhan, G., Stumvoll, M., Beilby, J., Pasquale, L.R., Feenstra, B., Bandinelli, S., Ordovas, J.M., Chan, A.T., Peters, U., Ohlsson, C., Gieger, C., Martin, N.G., Waldenberger, M., Siscovick, D.S., Raitakari, O., Eriksson, J.G., Mitchell, P., Hunter, D.J., Kraft, P., Rimm, E.B., Boomsma, D.I., Borecki, I.B., Loos, R.J., Wareham, N.J., Vollenweider, P., Caporaso, N., Grabe, H.J., Neuhouser, M.L., Wolffenbuttel, B.H., Hu, F.B., Hyppönen, E., Järvelin, M.R., Cupples, L.A., Franks, P.W., Ridker, P.M., van Duijn, C.M., Heiss, G., Metspalu, A., North, K.E., Ingelsson, E., Nettleton, J.A., van Dam, R.M., Chasman, D.I., The, Coffee, Cornelis, M.C., Byrne, E.M., Esko, T., Nalls, M.A., Ganna, A., Paynter, N., Monda, K.L., Amin, N., Fischer, K., Renstrom, F., Ngwa, J.S., Huikari, V., Cavadino, A., Nolte, I.M., Teumer, A., Yu, K., Marques-Vidal, P., Rawal, R., Manichaikul, A., Wojczynski, M.K., Vink, J.M., Zhao, J.H., Burlutsky, G., Lahti, J., Mikkilä, V., Lemaitre, R.N., Eriksson, J., Musani, S.K., Tanaka, T., Geller, F., Luan, J., Hui, J., Mägi, R., Dimitriou, M., Garcia, M.E., Ho, W.K., Wright, M.J., Rose, L.M., Magnusson, P.K., Pedersen, N.L., Couper, D., Oostra, B.A., Hofman, A., Ikram, M.A., Tiemeier, H.W., Uitterlinden, A.G., van Rooij, F.J., Barroso, I., Johansson, I., Xue, L., Kaakinen, M., Milani, L., Power, C., Snieder, H., Stolk, R.P., Baumeister, S.E., Biffar, R., Gu, F., Bastardot, F., Kutalik, Z., Jacobs, D.R., Forouhi, N.G., Mihailov, E., Lind, L., Lindgren, C., Michaëlsson, K., Morris, A., Jensen, M., Khaw, K.T., Luben, R.N., Wang, J.J., Männistö, S., Perälä, M.M., Kähönen, M., Lehtimäki, T., Viikari, J., Mozaffarian, D., Mukamal, K., Psaty, B.M., Döring, A., Heath, A.C., Montgomery, G.W., Dahmen, N., Carithers, T., Tucker, K.L., Ferrucci, L., Boyd, H.A., Melbye, M., Treur, J.L., Mellström, D., Hottenga, J.J., Prokopenko, I., Tönjes, A., Deloukas, P., Kanoni, S., Lorentzon, M., Houston, D.K., Liu, Y., Danesh, J., Rasheed, A., Mason, M.A., Zonderman, A.B., Franke, L., Kristal, B.S., Karjalainen, J., Reed, D.R., Westra, H.J., Evans, M.K., Saleheen, D., Harris, T.B., Dedoussis, G., Curhan, G., Stumvoll, M., Beilby, J., Pasquale, L.R., Feenstra, B., Bandinelli, S., Ordovas, J.M., Chan, A.T., Peters, U., Ohlsson, C., Gieger, C., Martin, N.G., Waldenberger, M., Siscovick, D.S., Raitakari, O., Eriksson, J.G., Mitchell, P., Hunter, D.J., Kraft, P., Rimm, E.B., Boomsma, D.I., Borecki, I.B., Loos, R.J., Wareham, N.J., Vollenweider, P., Caporaso, N., Grabe, H.J., Neuhouser, M.L., Wolffenbuttel, B.H., Hu, F.B., Hyppönen, E., Järvelin, M.R., Cupples, L.A., Franks, P.W., Ridker, P.M., van Duijn, C.M., Heiss, G., Metspalu, A., North, K.E., Ingelsson, E., Nettleton, J.A., van Dam, R.M., and Chasman, D.I.

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 × 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.

Published
2015

43. Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.

Author

FTO-Mortality Collaborating Group, Orho-Melander, M., Zillikens, C., Ikram, A., Hofman, A., Luan, J., Khaw, KT., Rose, LM., Läll, K., Mägi, R., Qi, L., Sun, Q., Harris, TB., Launer, LJ., Eiriksdottir, G., Kleber, ME., Delgado, G., Liu, Y., Garcia, M., Teumer, A., Grabe, H., Homuth, G., Jukema, JW., Ford, I., de Craen AJ., Gallacher, J., Yarnell, J., Mahabadi, AA., Nöthen, MM., Erbel, R., Stringham, HM., Boehnke, M., Amouyel, P., Ferrières, J., Arveiler, D., Kähönen, M., Nikus, K., Nieminen, T., Sanchez, A., Kivimaki, M., van Vliet-Ostaptchouk JV., Hampel, R., Thorand, B., De Faire, U., Nyberg, F., Kuh, D., Martin, NG., Montgomery, GW., Heath, AC., Madden, PA., Osmond, C., Pulizzi, N., Roswall, N., Halkjaer, J., Overvad, K., Uusitupa, M., Kinnunen, L., Lindström, J., Saramies, J., Keinänen-Kiukaanniemi, S., Uusitalo, H., Hussi, E., Baldassarre, D., Veglia, F., Humphries, S., Tremoli, E., Heitmann, B., Zimmermann, E., Ängquist, L.H., Mirza, S.S., Zhao, J.H., Chasman, D.I., Fischer, K., Qi, Q., Smith, A.V., Thinggaard, M., Jarczok, M.N., Nalls, M.A., Trompet, S., Timpson, N.J., Schmidt, B., Jackson, A.U., Lyytikäinen, L.P., Verweij, N., Mueller-Nurasyid, M., Vikström, M., Marques-Vidal, P., Wong, A., Meidtner, K., Middelberg, R.P., Strawbridge, R.J., Christiansen, L., Kyvik, K.O., Hamsten, A., Jääskeläinen, T., Tjønneland, A., Eriksson, J.G., Whitfield, J.B., Boeing, H., Hardy, R., Vollenweider, P., Leander, K., Peters, A., van der Harst, P., Kumari, M., Lehtimäki, T., Meirhaeghe, A., Tuomilehto, J., Jöckel, K.H., Ben-Shlomo, Y., Sattar, N., Baumeister, S.E., Davey Smith, G., Casas, J.P., Houston, D.K., März, W., Christensen, K., Gudnason, V., Hu, F.B., Metspalu, A., Ridker, P.M., Wareham, N.J., Loos, R.J., Tiemeier, H., Sonestedt, E., Sørensen, T.I., FTO-Mortality Collaborating Group, Orho-Melander, M., Zillikens, C., Ikram, A., Hofman, A., Luan, J., Khaw, KT., Rose, LM., Läll, K., Mägi, R., Qi, L., Sun, Q., Harris, TB., Launer, LJ., Eiriksdottir, G., Kleber, ME., Delgado, G., Liu, Y., Garcia, M., Teumer, A., Grabe, H., Homuth, G., Jukema, JW., Ford, I., de Craen AJ., Gallacher, J., Yarnell, J., Mahabadi, AA., Nöthen, MM., Erbel, R., Stringham, HM., Boehnke, M., Amouyel, P., Ferrières, J., Arveiler, D., Kähönen, M., Nikus, K., Nieminen, T., Sanchez, A., Kivimaki, M., van Vliet-Ostaptchouk JV., Hampel, R., Thorand, B., De Faire, U., Nyberg, F., Kuh, D., Martin, NG., Montgomery, GW., Heath, AC., Madden, PA., Osmond, C., Pulizzi, N., Roswall, N., Halkjaer, J., Overvad, K., Uusitupa, M., Kinnunen, L., Lindström, J., Saramies, J., Keinänen-Kiukaanniemi, S., Uusitalo, H., Hussi, E., Baldassarre, D., Veglia, F., Humphries, S., Tremoli, E., Heitmann, B., Zimmermann, E., Ängquist, L.H., Mirza, S.S., Zhao, J.H., Chasman, D.I., Fischer, K., Qi, Q., Smith, A.V., Thinggaard, M., Jarczok, M.N., Nalls, M.A., Trompet, S., Timpson, N.J., Schmidt, B., Jackson, A.U., Lyytikäinen, L.P., Verweij, N., Mueller-Nurasyid, M., Vikström, M., Marques-Vidal, P., Wong, A., Meidtner, K., Middelberg, R.P., Strawbridge, R.J., Christiansen, L., Kyvik, K.O., Hamsten, A., Jääskeläinen, T., Tjønneland, A., Eriksson, J.G., Whitfield, J.B., Boeing, H., Hardy, R., Vollenweider, P., Leander, K., Peters, A., van der Harst, P., Kumari, M., Lehtimäki, T., Meirhaeghe, A., Tuomilehto, J., Jöckel, K.H., Ben-Shlomo, Y., Sattar, N., Baumeister, S.E., Davey Smith, G., Casas, J.P., Houston, D.K., März, W., Christensen, K., Gudnason, V., Hu, F.B., Metspalu, A., Ridker, P.M., Wareham, N.J., Loos, R.J., Tiemeier, H., Sonestedt, E., and Sørensen, T.I.

Abstract

Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m(-2) ; 95% CI 0.28-0.32, P < 1 × 10(-32) ), WC (n = 152,631; 0.76 cm; 0.68-0.84, P < 1 × 10(-32) ) and FMI (n = 48,192; 0.17 kg m(-2) ; 0.13-0.22, P = 1.0 × 10(-13) ). Cox proportional hazard regression analyses for mortality showed that the hazards ratio (HR) for the minor allele of the FTO SNPs was 1.02 (1.00-1.04, P = 0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC (HR: 1.00; 0.98-1.03, P = 0.662) and for FMI (HR: 1.00; 0.96-1.04, P = 0.932). In conclusion, this study does not support that the FTO SNP is associated with all-cause mortality independently of the adiposity phenotypes.

Published
2015

44. Consumption of meat is associated with higher fasting glucose and insulin concentrations regardless of glucose and insulin genetic risk scores: A meta-analysis of 50,345 Caucasians

Author

Fretts, A.M. (Amanda M.), Follis, J.L. (Jack ), Nettleton, J.A. (Jennifer ), Lemaitre, R.N. (Rozenn ), Ngwa, J.S., Wojczynski, M.K. (Mary ), Kalafati, I.-P. (Ioanna-Panagiota), Varga, T.V. (Tibor V.), Frazier-Wood, A.C. (Alexis C.), Houston, D.K. (Denise), Lahti, J. (Jari), Ericson, U. (Ulrika), Hooven, E.H. (Edith) van den, Mikkilä, V. (Vera), Kiefte-de Jong, J.C. (Jessica), Mozaffarian, D. (Dariush), Rice, K.M. (Kenneth), Renström, F. (Frida), North, K.E. (Kari), McKeown, N.M. (Nicola ), Feitosa, M.F. (Mary Furlan), Kanoni, S. (Stavroula), Smith, C.E. (Caren), Garcia, M. (Melissa), Tiainen, A.-M. (Anna-Maija), Sonestedt, E. (Emily), Manichaikul, A. (Ani), Rooij, F.J.A. (Frank) van, Dimitriou, M. (Maria), Raitakari, O. (Olli), Pankow, J.S. (James), Djoussé, L. (Luc), Province, M.A. (Mike), Hu, F.B. (Frank), Lai, C.-Q. (Chao-Qiang), Keller, M.F. (Margaux), Perälä, M.-M. (Mia-Maria), Rotter, J.I. (Jerome I.), Hofman, A. (Albert), Graff, M.J. (Maud J.L.), Kähönen, M. (Mika), Mukamal, K. (Kenneth), Johansson, I. (Ingegerd), Ordovas, J.M. (Jose), Liu, Y. (YongMei), Männistö, S. (Satu), Uitterlinden, A.G. (André), Deloukas, P. (Panagiotis), Seppälä, I. (Ilkka), Psaty, B.M. (Bruce), Cupples, L.A. (Adrienne), Borecki, I.B. (Ingrid), Franks, P.W. (Paul W.), Arnett, D.K. (Donna), Nalls, M.A. (Michael), Hagen, K. (Knut), Orho-Melander, M. (Marju), Franco, O.H. (Oscar), Lehtimäki, T. (Terho), Dedoussis, G.V. (George), Meigs, J.B. (James), Siscovick, D.S. (David), Fretts, A.M. (Amanda M.), Follis, J.L. (Jack ), Nettleton, J.A. (Jennifer ), Lemaitre, R.N. (Rozenn ), Ngwa, J.S., Wojczynski, M.K. (Mary ), Kalafati, I.-P. (Ioanna-Panagiota), Varga, T.V. (Tibor V.), Frazier-Wood, A.C. (Alexis C.), Houston, D.K. (Denise), Lahti, J. (Jari), Ericson, U. (Ulrika), Hooven, E.H. (Edith) van den, Mikkilä, V. (Vera), Kiefte-de Jong, J.C. (Jessica), Mozaffarian, D. (Dariush), Rice, K.M. (Kenneth), Renström, F. (Frida), North, K.E. (Kari), McKeown, N.M. (Nicola ), Feitosa, M.F. (Mary Furlan), Kanoni, S. (Stavroula), Smith, C.E. (Caren), Garcia, M. (Melissa), Tiainen, A.-M. (Anna-Maija), Sonestedt, E. (Emily), Manichaikul, A. (Ani), Rooij, F.J.A. (Frank) van, Dimitriou, M. (Maria), Raitakari, O. (Olli), Pankow, J.S. (James), Djoussé, L. (Luc), Province, M.A. (Mike), Hu, F.B. (Frank), Lai, C.-Q. (Chao-Qiang), Keller, M.F. (Margaux), Perälä, M.-M. (Mia-Maria), Rotter, J.I. (Jerome I.), Hofman, A. (Albert), Graff, M.J. (Maud J.L.), Kähönen, M. (Mika), Mukamal, K. (Kenneth), Johansson, I. (Ingegerd), Ordovas, J.M. (Jose), Liu, Y. (YongMei), Männistö, S. (Satu), Uitterlinden, A.G. (André), Deloukas, P. (Panagiotis), Seppälä, I. (Ilkka), Psaty, B.M. (Bruce), Cupples, L.A. (Adrienne), Borecki, I.B. (Ingrid), Franks, P.W. (Paul W.), Arnett, D.K. (Donna), Nalls, M.A. (Michael), Hagen, K. (Knut), Orho-Melander, M. (Marju), Franco, O.H. (Oscar), Lehtimäki, T. (Terho), Dedoussis, G.V. (George), Meigs, J.B. (James), and Siscovick, D.S. (David)

Abstract

Background: Recent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown. Objective: We investigated the associations of meat intake and the interaction of meat with genotype on fasting glucose and insulin concentrations in Caucasians free of diabetes mellitus. Design: Fourteen studies that are part of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium participated in the analysis. Data were provided for up to 50,345 participants. Using linear regression within studies and a fixed-effects meta-analysis across studies, we examined 1) the associations of processed meat and unprocessed red meat intake with fasting glucose and insulin concentrations; and 2) the interactions of processed meat and unprocessed red meat with genetic risk score related to fasting glucose or insulin resistance on fasting glucose and insulin concentrations. Results: Processed meat was associated with higher fasting glucose, and unprocessed red meat was associated with both higher fasting glucose and fasting insulin concentrations after adjustment for potential confounders [not including body mass index (BMI)]. For every additional 50-g serving of processed meat per day, fasting glucose was 0.021 mmol/L (95% CI: 0.011, 0.030 mmol/L) higher. Every additional 100-g serving of unprocessed red meat per day was associated with a 0.037-mmol/L (95% CI: 0.023, 0.051-mmol/L) higher fasting glucose concentration and a 0.049-ln-pmol/L (95% CI: 0.035, 0.063-ln-pmol/L) higher fasting insulin concentration. After additional adjustment for BMI, observed associations were attenuated and no longer statistically significant. The association of processed meat and fasting insulin did not reach statistical significance after correction for multiple comparisons. Observed associations were not modified by genetic loci k

Published
2015
Full Text
View/download PDF

45. Dietary Intake, FTO genetic variants, and adiposity: A combined analysis of over 16,000 children and adolescents

Author

Qi, Q. (Qibin), Downer, M.K. (Mary K.), Kilpeläinen, T.O. (Tuomas), Taal, H.R. (Rob), Barton, S.J. (Sheila), Ntalla, I. (Ioanna), Standl, E. (Eberhard), Boraska, V. (Vesna), Huikari, V. (Ville), Kiefte-de Jong, J.C. (Jessica), KöRner, A. (Antje), Lakka, T.A. (Timo), Liu, G. (Gaifen), Magnusson, J. (Jessica), Okuda, M. (Masayuki), Raitakari, O. (Olli), Richmond, R.C. (Rebecca C.), Scott, R.A. (Robert), Bailey, M.E.S. (Mark), Scheuermann, K. (Kathrin), Holloway, J. (John), Inskip, H.M. (Hazel), Isasi, C.R. (Carmen R.), Mossavar-Rahmani, Y. (Yasmin), Jaddoe, V.W.V. (Vincent), Laitinen, J. (Jaana), Lindi, V. (Virpi), Melén, E. (Erik), Pitsiladis, Y. (Yannis), Pitkanen, N. (Niina), Snieder, H. (Harold), Heinrich, J. (Joachim), Timpson, N.J. (Nicholas), Wang, T. (Teng), Yuji, H. (Hinoda), Zeggini, E. (Eleftheria), Dedoussis, G.V. (George), Kaplan, R.C. (Robert), Wylie-Rosett, J. (Judith), Loos, R.J.F. (Ruth), Hu, F.B. (Frank), Qi, L. (Lu), Qi, Q. (Qibin), Downer, M.K. (Mary K.), Kilpeläinen, T.O. (Tuomas), Taal, H.R. (Rob), Barton, S.J. (Sheila), Ntalla, I. (Ioanna), Standl, E. (Eberhard), Boraska, V. (Vesna), Huikari, V. (Ville), Kiefte-de Jong, J.C. (Jessica), KöRner, A. (Antje), Lakka, T.A. (Timo), Liu, G. (Gaifen), Magnusson, J. (Jessica), Okuda, M. (Masayuki), Raitakari, O. (Olli), Richmond, R.C. (Rebecca C.), Scott, R.A. (Robert), Bailey, M.E.S. (Mark), Scheuermann, K. (Kathrin), Holloway, J. (John), Inskip, H.M. (Hazel), Isasi, C.R. (Carmen R.), Mossavar-Rahmani, Y. (Yasmin), Jaddoe, V.W.V. (Vincent), Laitinen, J. (Jaana), Lindi, V. (Virpi), Melén, E. (Erik), Pitsiladis, Y. (Yannis), Pitkanen, N. (Niina), Snieder, H. (Harold), Heinrich, J. (Joachim), Timpson, N.J. (Nicholas), Wang, T. (Teng), Yuji, H. (Hinoda), Zeggini, E. (Eleftheria), Dedoussis, G.V. (George), Kaplan, R.C. (Robert), Wylie-Rosett, J. (Judith), Loos, R.J.F. (Ruth), Hu, F.B. (Frank), and Qi, L. (Lu)

Abstract

The FTO gene harbors variation with the strongest effect on adiposity and obesity risk. Previous data support a role for FTO variation in influencing food intake. We conducted a combined analysis of 16,094 boys and girls aged 1-18 years from 14 studies to examine the following: 1) the association between the FTO rs9939609 variant (or a proxy) and total energy and macr

Published
2015
Full Text
View/download PDF

46. Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci

Author

He, M. (Meian), Xu, M. (Min), Zhang, B. (Ben), Liang, J. (Jun), Chen, P. (Ping), Lee, J.-Y. (Jong-Young), Johnson, T.A. (Todd A.), Li, H. (Huaixing), Yang, X. (Xiaobo), Dai, J. (Juncheng), Liang, L. (Liming), Gui, L. (Lixuan), Qi, Q., Huang, J. (Jian), Li, Y. (Yanping), Adair, L.S. (Linda), Aung, T. (Tin), Cai, Q. (Qiuyin), Cheng, C-Y. (Ching-Yu), Cho, M.-C. (Myeong-Chan), Cho, Y.S. (Yoon Shin), Chu, M. (Minjie), Cui, B. (Bin), Gao, Y. (Ying), Go, M.J. (Min Jin), Gu, D. (D.), Gu, W. (Weiqiong), Guo, H. (Huan), Hao, Y. (Yongchen), Hong, J. (Jie), Hu, Z. (Zhibin), Hu, Y. (Yanling), Huang, J. (Jianfeng), Hwang, J.-Y. (Joo-Yeon), Ikram, M.K. (Kamran), Jin, G. (Guangfu), Kang, D. (Daehee), Khor, C.C., Kim, B.-J. (Bong-Jo), Kim, H.T. (Hung Tae), Kubo, M. (Michiaki), Lee, J. (Jeannette), Lee, J. (Juyoung), Lee, N.R. (Nanette R.), Li, R. (Rui), Li, J. (Jun), Liu, J. (Jianjun), Longe, J. (Jirong), Lu, W. (Wei), Lu, X. (Xiangfeng), Miao, X. (Xiaoping), Okada, Y. (Yukinori), Ong, R.T.H. (Rick Twee-Hee), Qiu, G. (Gaokun), Seielstad, M. (Mark), Sim, X. (Xueling), Song, H. (Huaidong), Takeuchi, F. (Fumihiko), Tanaka, T. (Toshihiro), Taylor, P.R. (Phil R.), Wang, L. (Laiyuan), Wang, W. (Weiqing), Wang, Y. (Yiqin), Wu, C. (Chen), Wu, Y. (Ying), Xiang, Y.-B. (Yong-Bing), Yamamoto, K. (Ken), Yang, H. (Handong), Liao, M. (Ming), Yokota, M. (Mitsuhiro), Young, T. (Terri), Zhang, X. (Xiaomin), Kato, N. (Norihiro), Wang, Q. (Qing), Zheng, W. (Wei), Hu, F.B. (Frank), Lin, D. (Dongxin), Shen, H. (Hongbing), Teo, Y.Y. (Yik Ying), Mo, Z. (Zengnan), Wong, T.Y. (Tien Yin), Lin, X. (Xu), Mohlke, K.L. (Karen), Ning, G. (Guang), Tsunoda, T. (Tatsuhiko), Han, B.-G., Shu, X.-O. (Xiao-Ou), Tai, E.S. (Shyong), Wu, T. (Tangchun), Qi, L. (Lu), He, M. (Meian), Xu, M. (Min), Zhang, B. (Ben), Liang, J. (Jun), Chen, P. (Ping), Lee, J.-Y. (Jong-Young), Johnson, T.A. (Todd A.), Li, H. (Huaixing), Yang, X. (Xiaobo), Dai, J. (Juncheng), Liang, L. (Liming), Gui, L. (Lixuan), Qi, Q., Huang, J. (Jian), Li, Y. (Yanping), Adair, L.S. (Linda), Aung, T. (Tin), Cai, Q. (Qiuyin), Cheng, C-Y. (Ching-Yu), Cho, M.-C. (Myeong-Chan), Cho, Y.S. (Yoon Shin), Chu, M. (Minjie), Cui, B. (Bin), Gao, Y. (Ying), Go, M.J. (Min Jin), Gu, D. (D.), Gu, W. (Weiqiong), Guo, H. (Huan), Hao, Y. (Yongchen), Hong, J. (Jie), Hu, Z. (Zhibin), Hu, Y. (Yanling), Huang, J. (Jianfeng), Hwang, J.-Y. (Joo-Yeon), Ikram, M.K. (Kamran), Jin, G. (Guangfu), Kang, D. (Daehee), Khor, C.C., Kim, B.-J. (Bong-Jo), Kim, H.T. (Hung Tae), Kubo, M. (Michiaki), Lee, J. (Jeannette), Lee, J. (Juyoung), Lee, N.R. (Nanette R.), Li, R. (Rui), Li, J. (Jun), Liu, J. (Jianjun), Longe, J. (Jirong), Lu, W. (Wei), Lu, X. (Xiangfeng), Miao, X. (Xiaoping), Okada, Y. (Yukinori), Ong, R.T.H. (Rick Twee-Hee), Qiu, G. (Gaokun), Seielstad, M. (Mark), Sim, X. (Xueling), Song, H. (Huaidong), Takeuchi, F. (Fumihiko), Tanaka, T. (Toshihiro), Taylor, P.R. (Phil R.), Wang, L. (Laiyuan), Wang, W. (Weiqing), Wang, Y. (Yiqin), Wu, C. (Chen), Wu, Y. (Ying), Xiang, Y.-B. (Yong-Bing), Yamamoto, K. (Ken), Yang, H. (Handong), Liao, M. (Ming), Yokota, M. (Mitsuhiro), Young, T. (Terri), Zhang, X. (Xiaomin), Kato, N. (Norihiro), Wang, Q. (Qing), Zheng, W. (Wei), Hu, F.B. (Frank), Lin, D. (Dongxin), Shen, H. (Hongbing), Teo, Y.Y. (Yik Ying), Mo, Z. (Zengnan), Wong, T.Y. (Tien Yin), Lin, X. (Xu), Mohlke, K.L. (Karen), Ning, G. (Guang), Tsunoda, T. (Tatsuhiko), Han, B.-G., Shu, X.-O. (Xiao-Ou), Tai, E.S. (Shyong), Wu, T. (Tangchun), and Qi, L. (Lu)

Published
2015
Full Text
View/download PDF

47. Gene × dietary pattern interactions in obesity: Analysis of up to 68 317 adults of European ancestry

Author

Nettleton, J.A., Follis, J.L. (Jack ), Ngwa, J.S., Smith, C.E. (Caren), Ahmad, S. (Shafqat), Tanaka, T. (Toshiko), Wojczynski, M.K. (Mary ), Voortman, R.G. (Trudy), Lemaitre, R.N. (Rozenn ), Kristiansson, K. (Kati), Nuotio, M.-L. (Marja-Liisa), Houston, D.K., Perälä, M.-M. (Mia-Maria), Qi, Q., Sonestedt, E. (Emily), Manichaikul, A. (Ani), Kanoni, S. (Stavroula), Ganna, A. (Andrea), Mikkilä, V. (Vera), North, K.E. (Kari), Siscovick, D.S. (David), Harald, K. (Kennet), McKeown, N.M. (Nicola ), Johansson, I. (Ingegerd), Rissanen, H. (Harri), Liu, Y. (YongMei), Lahti, J. (Jari), Hu, F.B. (Frank), Bandinelli, S. (Stefania), Rukh, G. (Gull), Rich, S.S. (Stephen S.), Booij, L. (Lisanne), Dmitriou, M. (Maria), Ax, E. (Erika), Raitakari, O.T. (Olli T.), Mukamal, K. (Kenneth), Männistö, S. (Satu), Hallmans, G. (Göran), Jula, A. (Antti), Ericson, U. (Ulrika), Jacobs, D.R. (David), Rooij, F.J.A. (Frank) van, Deloukas, P. (Panagiotis), Sjøgren, P. (Per), Kähönen, M. (Mika), Djoussé, L. (Luc), Perola, M. (Markus), Barroso, I.E. (Inês), Hofman, A. (Albert), Stirrups, K. (Kathy), Viikari, J. (Jorma), Uitterlinden, A.G. (André), Kalafati, I.-P. (Ioanna-Panagiota), Franco, O.H. (Oscar), Mozaffarian, D. (Dariush), Salomaa, V. (Veikko), Borecki, I.B. (Ingrid), Knekt, P., Kritchevsky, S.B. (Stephen), Hagen, K. (Knut), Dedoussis, G.V. (George), Qi, L. (Lu), Ferrucci, L. (Luigi), Orho-Melander, M. (Marju), Zillikens, M.C. (Carola), Ingelsson, E. (Erik), Lehtimäki, T. (Terho), Renström, F. (Frida), Cupples, L.A. (Adrienne), Loos, R.J.F. (Ruth), Franks, P.W. (Paul), Nettleton, J.A., Follis, J.L. (Jack ), Ngwa, J.S., Smith, C.E. (Caren), Ahmad, S. (Shafqat), Tanaka, T. (Toshiko), Wojczynski, M.K. (Mary ), Voortman, R.G. (Trudy), Lemaitre, R.N. (Rozenn ), Kristiansson, K. (Kati), Nuotio, M.-L. (Marja-Liisa), Houston, D.K., Perälä, M.-M. (Mia-Maria), Qi, Q., Sonestedt, E. (Emily), Manichaikul, A. (Ani), Kanoni, S. (Stavroula), Ganna, A. (Andrea), Mikkilä, V. (Vera), North, K.E. (Kari), Siscovick, D.S. (David), Harald, K. (Kennet), McKeown, N.M. (Nicola ), Johansson, I. (Ingegerd), Rissanen, H. (Harri), Liu, Y. (YongMei), Lahti, J. (Jari), Hu, F.B. (Frank), Bandinelli, S. (Stefania), Rukh, G. (Gull), Rich, S.S. (Stephen S.), Booij, L. (Lisanne), Dmitriou, M. (Maria), Ax, E. (Erika), Raitakari, O.T. (Olli T.), Mukamal, K. (Kenneth), Männistö, S. (Satu), Hallmans, G. (Göran), Jula, A. (Antti), Ericson, U. (Ulrika), Jacobs, D.R. (David), Rooij, F.J.A. (Frank) van, Deloukas, P. (Panagiotis), Sjøgren, P. (Per), Kähönen, M. (Mika), Djoussé, L. (Luc), Perola, M. (Markus), Barroso, I.E. (Inês), Hofman, A. (Albert), Stirrups, K. (Kathy), Viikari, J. (Jorma), Uitterlinden, A.G. (André), Kalafati, I.-P. (Ioanna-Panagiota), Franco, O.H. (Oscar), Mozaffarian, D. (Dariush), Salomaa, V. (Veikko), Borecki, I.B. (Ingrid), Knekt, P., Kritchevsky, S.B. (Stephen), Hagen, K. (Knut), Dedoussis, G.V. (George), Qi, L. (Lu), Ferrucci, L. (Luigi), Orho-Melander, M. (Marju), Zillikens, M.C. (Carola), Ingelsson, E. (Erik), Lehtimäki, T. (Terho), Renström, F. (Frida), Cupples, L.A. (Adrienne), Loos, R.J.F. (Ruth), and Franks, P.W. (Paul)

Abstract

Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS

Published
2015
Full Text
View/download PDF

48. Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

Author

Cornelis, M. (Marilyn), Byrne, E.M., Esko, T. (Tõnu), Nalls, M.A. (Michael), Ganna, A. (Andrea), Paynter, N.P. (Nina), Monda, K.L. (Keri), Amin, N. (Najaf), Fischer, K. (Krista), Renström, F. (Frida), Ngwa, J.S., Huikari, V. (Ville), Cavadino, A. (Alana), Nolte, I.M. (Ilja M.), Teumer, A. (Alexander), Yu, K., Marques-Vidal, P. (Pedro), Rawal, R., Manichaikul, A. (Ani), Wojczynski, M.K. (Mary ), Vink, J.M., Zhao, J.H. (Jing Hua), Burlutsky, G. (George), Lahti, J. (Jari), Mikkilä, V. (Vera), Lemaitre, R.N. (Rozenn ), Eriksson, J., Musani, S. (Solomon), Tanaka, T., Geller, F. (Frank), Luan, J., Hui, J., Mägi, R. (Reedik), Dimitriou, M. (Maria), Garcia, M. (Melissa), Ho, W.-K., Wright, M.J. (Margaret), Rose, L.M. (Lynda M.), Magnusson, P.K.E. (Patrik K. E.), Pedersen, N.L. (Nancy L.), Couper, D.J. (David), Oostra, B.A. (Ben), Hofman, A. (Albert), Ikram, M.A. (Arfan), Tiemeier, H.W. (Henning), Uitterlinden, A.G. (André), Rooij, F.J.A. (Frank) van, Barroso, I., Johansson, I. (Ingegerd), Xue, L. (Luting), Kaakinen, M. (Marika), Milani, L. (Lili), Power, C. (Christine), Snieder, H. (Harold), Stolk, R.P., Baumeister, S.E. (Sebastian), Biffar, R., Gu, F., Bastardot, F. (Francois), Kutalik, Z., Jacobs, D.R. (David), Forouhi, N.G. (Nita G.), Mihailov, E. (Evelin), Lind, L. (Lars), Lindgren, C., Michaëlsson, K., Morris, A.P. (Andrew), Jensen, M.K. (Majken K.), Khaw, K.T., Luben, R.N. (Robert), Wang, J.J., Männistö, S. (Satu), Perälä, M.-M., Kähönen, M. (Mika), Lehtimäki, T. (Terho), Viikari, J. (Jorma), Mozaffarian, D., Mukamal, K. (Kenneth), Psaty, B.M. (Bruce), Döring, A., Heath, A.C. (Andrew C.), Montgomery, G.W. (Grant W.), Dahmen, N. (N.), Carithers, T., Tucker, K.L., Ferrucci, L. (Luigi), Boyd, H.A., Melbye, M. (Mads), Treur, J.L., Mellström, D. (Dan), Hottenga, J.J. (Jouke Jan), Prokopenko, I. (Inga), Tönjes, A. (Anke), Deloukas, P. (Panagiotis), Kanoni, S. (Stavroula), Lorentzon, M. (Mattias), Houston, D.K., Liu, Y., Danesh, J. (John), Rasheed, A., Mason, M.A., Zonderman, A.B., Franke, L. (Lude), Kristal, B.S., Karjalainen, J. (Juha), Reed, D.R., Westra, H.-J., Evans, M.K. (Michele), Saleheen, D., Harris, T.B. (Tamara), Dedoussis, G.V. (George V.), Curhan, G.C. (Gary), Stumvoll, M. (Michael), Beilby, J. (John), Pasquale, L.R., Feenstra, B., Bandinelli, S., Ordovas, J.M., Chan, A.T., Peters, U. (Ulrike), Ohlsson, C. (Claes), Gieger, C. (Christian), Martin, N.G. (Nicholas), Waldenberger, M. (Melanie), Siscovick, D.S. (David), Raitakari, O. (Olli), Eriksson, J.G. (Johan G.), Mitchell, P. (Paul), Hunter, D. (David), Kraft, P. (Peter), Rimm, E.B. (Eric B.), Boomsma, D.I. (Dorret), Borecki, I.B. (Ingrid), Loos, R.J.F. (Ruth), Wareham, N.J. (Nick), Vollenweider, P.K. (Peter K.), Caporaso, N., Grabe, H.J. (Hans Jörgen), Neuhouser, M.L. (Marian L.), Wolffenbuttel, B.H.R. (Bruce H. R.), Hu, F.B. (Frank), Hypponen, E. (Elina), Jarvelin, M.-R. (Marjo-Riitta), Cupples, L.A. (Adrienne), Franks, P.W., Ridker, P.M. (Paul), Duijn, C.M. (Cornelia) van, Heiss, G. (Gerardo), Metspalu, A. (Andres), North, K.E. (Kari), Ingelsson, E. (Erik), Nettleton, J.A., Dam, R.M. (Rob) van, Chasman, D.I. (Daniel), Cornelis, M. (Marilyn), Byrne, E.M., Esko, T. (Tõnu), Nalls, M.A. (Michael), Ganna, A. (Andrea), Paynter, N.P. (Nina), Monda, K.L. (Keri), Amin, N. (Najaf), Fischer, K. (Krista), Renström, F. (Frida), Ngwa, J.S., Huikari, V. (Ville), Cavadino, A. (Alana), Nolte, I.M. (Ilja M.), Teumer, A. (Alexander), Yu, K., Marques-Vidal, P. (Pedro), Rawal, R., Manichaikul, A. (Ani), Wojczynski, M.K. (Mary ), Vink, J.M., Zhao, J.H. (Jing Hua), Burlutsky, G. (George), Lahti, J. (Jari), Mikkilä, V. (Vera), Lemaitre, R.N. (Rozenn ), Eriksson, J., Musani, S. (Solomon), Tanaka, T., Geller, F. (Frank), Luan, J., Hui, J., Mägi, R. (Reedik), Dimitriou, M. (Maria), Garcia, M. (Melissa), Ho, W.-K., Wright, M.J. (Margaret), Rose, L.M. (Lynda M.), Magnusson, P.K.E. (Patrik K. E.), Pedersen, N.L. (Nancy L.), Couper, D.J. (David), Oostra, B.A. (Ben), Hofman, A. (Albert), Ikram, M.A. (Arfan), Tiemeier, H.W. (Henning), Uitterlinden, A.G. (André), Rooij, F.J.A. (Frank) van, Barroso, I., Johansson, I. (Ingegerd), Xue, L. (Luting), Kaakinen, M. (Marika), Milani, L. (Lili), Power, C. (Christine), Snieder, H. (Harold), Stolk, R.P., Baumeister, S.E. (Sebastian), Biffar, R., Gu, F., Bastardot, F. (Francois), Kutalik, Z., Jacobs, D.R. (David), Forouhi, N.G. (Nita G.), Mihailov, E. (Evelin), Lind, L. (Lars), Lindgren, C., Michaëlsson, K., Morris, A.P. (Andrew), Jensen, M.K. (Majken K.), Khaw, K.T., Luben, R.N. (Robert), Wang, J.J., Männistö, S. (Satu), Perälä, M.-M., Kähönen, M. (Mika), Lehtimäki, T. (Terho), Viikari, J. (Jorma), Mozaffarian, D., Mukamal, K. (Kenneth), Psaty, B.M. (Bruce), Döring, A., Heath, A.C. (Andrew C.), Montgomery, G.W. (Grant W.), Dahmen, N. (N.), Carithers, T., Tucker, K.L., Ferrucci, L. (Luigi), Boyd, H.A., Melbye, M. (Mads), Treur, J.L., Mellström, D. (Dan), Hottenga, J.J. (Jouke Jan), Prokopenko, I. (Inga), Tönjes, A. (Anke), Deloukas, P. (Panagiotis), Kanoni, S. (Stavroula), Lorentzon, M. (Mattias), Houston, D.K., Liu, Y., Danesh, J. (John), Rasheed, A., Mason, M.A., Zonderman, A.B., Franke, L. (Lude), Kristal, B.S., Karjalainen, J. (Juha), Reed, D.R., Westra, H.-J., Evans, M.K. (Michele), Saleheen, D., Harris, T.B. (Tamara), Dedoussis, G.V. (George V.), Curhan, G.C. (Gary), Stumvoll, M. (Michael), Beilby, J. (John), Pasquale, L.R., Feenstra, B., Bandinelli, S., Ordovas, J.M., Chan, A.T., Peters, U. (Ulrike), Ohlsson, C. (Claes), Gieger, C. (Christian), Martin, N.G. (Nicholas), Waldenberger, M. (Melanie), Siscovick, D.S. (David), Raitakari, O. (Olli), Eriksson, J.G. (Johan G.), Mitchell, P. (Paul), Hunter, D. (David), Kraft, P. (Peter), Rimm, E.B. (Eric B.), Boomsma, D.I. (Dorret), Borecki, I.B. (Ingrid), Loos, R.J.F. (Ruth), Wareham, N.J. (Nick), Vollenweider, P.K. (Peter K.), Caporaso, N., Grabe, H.J. (Hans Jörgen), Neuhouser, M.L. (Marian L.), Wolffenbuttel, B.H.R. (Bruce H. R.), Hu, F.B. (Frank), Hypponen, E. (Elina), Jarvelin, M.-R. (Marjo-Riitta), Cupples, L.A. (Adrienne), Franks, P.W., Ridker, P.M. (Paul), Duijn, C.M. (Cornelia) van, Heiss, G. (Gerardo), Metspalu, A. (Andres), North, K.E. (Kari), Ingelsson, E. (Erik), Nettleton, J.A., Dam, R.M. (Rob) van, and Chasman, D.I. (Daniel)

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-t

Published
2015
Full Text
View/download PDF

49. Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci

Author

Gaulton, K. (Kyle), Ferreira, T. (Teresa), Lee, Y. (Yeji), Raimondo, A. (Anne), Mägi, R. (Reedik), Reschen, M.E. (Michael E.), Mahajan, A. (Anubha), Locke, A. (Adam), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil), Scott, R.A. (Robert), Prokopenko, I. (Inga), Scott, L.J. (Laura), Green, T. (Todd), Sparsø, T. (Thomas), Thuillier, D. (Dorothee), Yengo, L. (Loic), Grallert, H. (Harald), Wahl, S. (Simone), Frånberg, M. (Mattias), Strawbridge, R.J. (Rona), Kestler, H. (Hans), Chheda, H. (Himanshu), Eisele, L. (Lewin), Gustafsson, S. (Stefan), Steinthorsdottir, V. (Valgerdur), Thorleifsson, G. (Gudmar), Qi, L. (Lu), Karssen, L.C. (Lennart), Leeuwen, E.M. (Elisa) van, Willems, S.M. (Sara), Li, M. (Man), Chen, H. (Han), Fuchsberger, C. (Christian), Kwan, P. (Phoenix), Ma, C. (Clement), Linderman, M. (Michael), Lu, Y. (Yingchang), Thomsen, S.K. (Soren K.), Rundle, J.K. (Jana K.), Beer, N.L. (Nicola L.), Bunt, M. (Martijn) van de, Chalisey, A. (Anil), Kang, H.M. (Hyun Min), Voight, B.F. (Benjamin), Abecasis, G.R. (Gonçalo), Almgren, P. (Peter), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Benediktsson, R. (Rafn), Blüher, M. (Matthias), Boeing, H. (Heiner), Bonnycastle, L.L. (Lori), Bottinger, E.P. (Erwin P.), Burtt, N.P. (Noël), Carey, J. (Jason), Charpentier, G. (Guillaume), Chines, P.S. (Peter), Cornelis, M. (Marilyn), Couper, D.J. (David J.), Crenshaw, A. (Andrew), Dam, R.M. (Rob) van, Doney, A.S.F. (Alex), Dorkhan, M. (Mozhgan), Edkins, T. (Ted), Eriksson, J.G. (Johan G.), Esko, T. (Tõnu), Eury, E. (Elodie), Fadista, J. (João), Flannick, J. (Jason), Fontanillas, P. (Pierre), Fox, C.S. (Caroline), Franks, P.W. (Paul W.), Gertow, K. (Karl), Gieger, C. (Christian), Gigante, B. (Bruna), Gottesman, R.F. (Rebecca), Grant, G.B. (George), Grarup, N. (Niels), Groves, C.J. (Christopher J.), Hassinen, M. (Maija), Have, C.T. (Christian T.), Herder, C. (Christian), Holmen, O.L. (Oddgeir), Hreidarsson, A.B. (Astradur), Humphries, S.E. (Steve E.), Hunter, D.J. (David J.), Jackson, A.U. (Anne), Jonsson, A. (Anna), Jørgensen, M.E. (Marit E.), Jørgensen, T. (Torben), Kao, W.H.L. (Wen), Kerrison, N.D. (Nicola D.), Kinnunen, L. (Leena), Klopp, N. (Norman), Kong, A. (Augustine), Kovacs, P. (Peter), Kraft, P. (Peter), Kravic, J. (Jasmina), Langford, C. (Cordelia), Leander, K. (Karin), Liang, L. (Liming), Lichtner, P. (Peter), Lindgren, C.M. (Cecilia M.), Lindholm, B. (Bengt), Linneberg, A. (Allan), Liu, C.-T. (Ching-Ti), Lobbens, S. (Stéphane), Luan, J. (Jian'fan), Lyssenko, V. (Valeriya), Männistö, S. (Satu), McLeod, O. (Olga), Meyer, J. (Jobst), Mihailov, E. (Evelin), Mirza, G. (Ghazala), Mühleisen, T.W. (Thomas), Müller-Nurasyid, M. (Martina), Navarro, C. (Carmen), Nöthen, M.M. (Markus), Oskolkov, N.N. (Nikolay N.), Owen, K.R. (Katharine), Palli, D. (Domenico), Pechlivanis, S. (Sonali), Peltonen, L. (Leena Johanna), Perry, J.R.B. (John), Platou, C.P. (Carl), Roden, M. (Michael), Ruderfer, D. (Douglas), Rybin, D. (Denis), Van Der Schouw, Y.T. (Yvonne T.), Sennblad, B. (Bengt), Sigurosson, G. (Gunnar), Stancáková, A. (Alena), Steinbach, D., Storm, P. (Petter), Strauch, K. (Konstantin), Stringham, H.M. (Heather), Sun, Q., Thorand, B. (Barbara), Tikkanen, E. (Emmi), Tönjes, A. (Anke), Trakalo, J. (Joseph), Tremoli, E. (Elena), Tuomi, T. (Tiinamaija), Wennauer, R. (Roman), Wiltshire, S. (Steven), Wood, A.R. (Andrew), Zeggini, E. (Eleftheria), Dunham, I. (Ian), Birney, E. (Ewan), Pasquali, L. (Lorenzo), Ferrer, J. (Jorge), Loos, R.J.F. (Ruth), Dupuis, J. (Josée), Florez, J.C. (Jose), Boerwinkle, E.A. (Eric), Pankow, J.S. (James), Duijn, C.M. (Cornelia) van, Sijbrands, E.J.G. (Eric), Meigs, J.B. (James B.), Hu, F.B. (Frank), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Lakka, T.A. (Timo), Rauramaa, R. (Rainer), Stumvoll, M. (Michael), Pedersen, N.L. (Nancy L.), Lind, L. (Lars), Keinanen-Kiukaanniemi, S. (Sirkka), Korpi-Hyövälti, E. (Eeva), Saaristo, T. (Timo), Saltevo, J. (Juha), Kuusisto, J. (Johanna), Laakso, M. (Markku), Metspalu, A. (Andres), Erbel, R. (Raimund), Jöckel, K.-H. (Karl-Heinz), Moebus, S. (Susanne), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Ingelsson, E. (Erik), Boehm, B.O. (Bernhard), Bergman, R.N. (Richard N.), Collins, F.S. (Francis S.), Mohlke, K.L. (Karen L.), Koistinen, H. (Heikki), Tuomilehto, J. (Jaakko), Hveem, K. (Kristian), Njølstad, I. (Inger), Deloukas, P. (Panagiotis), Donnelly, P.J. (Peter J.), Frayling, T.M. (Timothy), Hattersley, A.T. (Andrew), Faire, U. (Ulf) de, Hamsten, A. (Anders), Illig, T. (Thomas), Peters, A. (Annette), Cauchi, S. (Stephane), Sladek, R. (Rob), Froguel, P. (Philippe), Hansen, T. (Torben), Pedersen, O. (Oluf), Morris, A.D. (Andrew), Palmer, C.N.A. (Collin N. A.), Kathiresan, S. (Sekar), Melander, O. (Olle), Nilsson, P.M. (Peter M.), Groop, L. (Leif), Barroso, I.E. (Inês), Langenberg, C. (Claudia), Wareham, N.J. (Nicholas J.), O'Callaghan, C.A. (Christopher A.), Gloyn, A.L. (Anna), Altshuler, D. (David), Boehnke, M. (Michael), Teslovich, T.M. (Tanya M.), McCarthy, M.I. (Mark), Morris, A.P. (Andrew), Gaulton, K. (Kyle), Ferreira, T. (Teresa), Lee, Y. (Yeji), Raimondo, A. (Anne), Mägi, R. (Reedik), Reschen, M.E. (Michael E.), Mahajan, A. (Anubha), Locke, A. (Adam), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil), Scott, R.A. (Robert), Prokopenko, I. (Inga), Scott, L.J. (Laura), Green, T. (Todd), Sparsø, T. (Thomas), Thuillier, D. (Dorothee), Yengo, L. (Loic), Grallert, H. (Harald), Wahl, S. (Simone), Frånberg, M. (Mattias), Strawbridge, R.J. (Rona), Kestler, H. (Hans), Chheda, H. (Himanshu), Eisele, L. (Lewin), Gustafsson, S. (Stefan), Steinthorsdottir, V. (Valgerdur), Thorleifsson, G. (Gudmar), Qi, L. (Lu), Karssen, L.C. (Lennart), Leeuwen, E.M. (Elisa) van, Willems, S.M. (Sara), Li, M. (Man), Chen, H. (Han), Fuchsberger, C. (Christian), Kwan, P. (Phoenix), Ma, C. (Clement), Linderman, M. (Michael), Lu, Y. (Yingchang), Thomsen, S.K. (Soren K.), Rundle, J.K. (Jana K.), Beer, N.L. (Nicola L.), Bunt, M. (Martijn) van de, Chalisey, A. (Anil), Kang, H.M. (Hyun Min), Voight, B.F. (Benjamin), Abecasis, G.R. (Gonçalo), Almgren, P. (Peter), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Benediktsson, R. (Rafn), Blüher, M. (Matthias), Boeing, H. (Heiner), Bonnycastle, L.L. (Lori), Bottinger, E.P. (Erwin P.), Burtt, N.P. (Noël), Carey, J. (Jason), Charpentier, G. (Guillaume), Chines, P.S. (Peter), Cornelis, M. (Marilyn), Couper, D.J. (David J.), Crenshaw, A. (Andrew), Dam, R.M. (Rob) van, Doney, A.S.F. (Alex), Dorkhan, M. (Mozhgan), Edkins, T. (Ted), Eriksson, J.G. (Johan G.), Esko, T. (Tõnu), Eury, E. (Elodie), Fadista, J. (João), Flannick, J. (Jason), Fontanillas, P. (Pierre), Fox, C.S. (Caroline), Franks, P.W. (Paul W.), Gertow, K. (Karl), Gieger, C. (Christian), Gigante, B. (Bruna), Gottesman, R.F. (Rebecca), Grant, G.B. (George), Grarup, N. (Niels), Groves, C.J. (Christopher J.), Hassinen, M. (Maija), Have, C.T. (Christian T.), Herder, C. (Christian), Holmen, O.L. (Oddgeir), Hreidarsson, A.B. (Astradur), Humphries, S.E. (Steve E.), Hunter, D.J. (David J.), Jackson, A.U. (Anne), Jonsson, A. (Anna), Jørgensen, M.E. (Marit E.), Jørgensen, T. (Torben), Kao, W.H.L. (Wen), Kerrison, N.D. (Nicola D.), Kinnunen, L. (Leena), Klopp, N. (Norman), Kong, A. (Augustine), Kovacs, P. (Peter), Kraft, P. (Peter), Kravic, J. (Jasmina), Langford, C. (Cordelia), Leander, K. (Karin), Liang, L. (Liming), Lichtner, P. (Peter), Lindgren, C.M. (Cecilia M.), Lindholm, B. (Bengt), Linneberg, A. (Allan), Liu, C.-T. (Ching-Ti), Lobbens, S. (Stéphane), Luan, J. (Jian'fan), Lyssenko, V. (Valeriya), Männistö, S. (Satu), McLeod, O. (Olga), Meyer, J. (Jobst), Mihailov, E. (Evelin), Mirza, G. (Ghazala), Mühleisen, T.W. (Thomas), Müller-Nurasyid, M. (Martina), Navarro, C. (Carmen), Nöthen, M.M. (Markus), Oskolkov, N.N. (Nikolay N.), Owen, K.R. (Katharine), Palli, D. (Domenico), Pechlivanis, S. (Sonali), Peltonen, L. (Leena Johanna), Perry, J.R.B. (John), Platou, C.P. (Carl), Roden, M. (Michael), Ruderfer, D. (Douglas), Rybin, D. (Denis), Van Der Schouw, Y.T. (Yvonne T.), Sennblad, B. (Bengt), Sigurosson, G. (Gunnar), Stancáková, A. (Alena), Steinbach, D., Storm, P. (Petter), Strauch, K. (Konstantin), Stringham, H.M. (Heather), Sun, Q., Thorand, B. (Barbara), Tikkanen, E. (Emmi), Tönjes, A. (Anke), Trakalo, J. (Joseph), Tremoli, E. (Elena), Tuomi, T. (Tiinamaija), Wennauer, R. (Roman), Wiltshire, S. (Steven), Wood, A.R. (Andrew), Zeggini, E. (Eleftheria), Dunham, I. (Ian), Birney, E. (Ewan), Pasquali, L. (Lorenzo), Ferrer, J. (Jorge), Loos, R.J.F. (Ruth), Dupuis, J. (Josée), Florez, J.C. (Jose), Boerwinkle, E.A. (Eric), Pankow, J.S. (James), Duijn, C.M. (Cornelia) van, Sijbrands, E.J.G. (Eric), Meigs, J.B. (James B.), Hu, F.B. (Frank), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Lakka, T.A. (Timo), Rauramaa, R. (Rainer), Stumvoll, M. (Michael), Pedersen, N.L. (Nancy L.), Lind, L. (Lars), Keinanen-Kiukaanniemi, S. (Sirkka), Korpi-Hyövälti, E. (Eeva), Saaristo, T. (Timo), Saltevo, J. (Juha), Kuusisto, J. (Johanna), Laakso, M. (Markku), Metspalu, A. (Andres), Erbel, R. (Raimund), Jöckel, K.-H. (Karl-Heinz), Moebus, S. (Susanne), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Ingelsson, E. (Erik), Boehm, B.O. (Bernhard), Bergman, R.N. (Richard N.), Collins, F.S. (Francis S.), Mohlke, K.L. (Karen L.), Koistinen, H. (Heikki), Tuomilehto, J. (Jaakko), Hveem, K. (Kristian), Njølstad, I. (Inger), Deloukas, P. (Panagiotis), Donnelly, P.J. (Peter J.), Frayling, T.M. (Timothy), Hattersley, A.T. (Andrew), Faire, U. (Ulf) de, Hamsten, A. (Anders), Illig, T. (Thomas), Peters, A. (Annette), Cauchi, S. (Stephane), Sladek, R. (Rob), Froguel, P. (Philippe), Hansen, T. (Torben), Pedersen, O. (Oluf), Morris, A.D. (Andrew), Palmer, C.N.A. (Collin N. A.), Kathiresan, S. (Sekar), Melander, O. (Olle), Nilsson, P.M. (Peter M.), Groop, L. (Leif), Barroso, I.E. (Inês), Langenberg, C. (Claudia), Wareham, N.J. (Nicholas J.), O'Callaghan, C.A. (Christopher A.), Gloyn, A.L. (Anna), Altshuler, D. (David), Boehnke, M. (Michael), Teslovich, T.M. (Tanya M.), McCarthy, M.I. (Mark), and Morris, A.P. (Andrew)

Abstract

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.

Published
2015
Full Text
View/download PDF

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

Author

Lunetta, K.L. (Kathryn), Day, F.R. (Felix), Sulem, P. (Patrick), Ruth, K.S. (Katherine S.), Tung, J.Y. (Joyce Y.), Hinds, D.A. (David A.), Esko, T. (Tõnu), Elks, C.E. (Cathy), Altmaier, E.L. (Elizabeth), He, C. (Chunyan), Huffman, J.E. (Jennifer), Mihailov, E. (Evelin), Porcu, E. (Eleonora), Robino, A. (Antonietta), Rose, L.M. (Lynda), Schick, U.M. (Ursula), Stolk, L. (Lisette), Teumer, A. (Alexander), Thompson, D. (Deborah), Traglia, M. (Michela), Wang, C.A. (Carol A.), Yerges-Armstrong, L.M. (Laura), Antoniou, A.C. (Antonis), Barbieri, C. (Caterina), Coviello, A.D. (Andrea), Cucca, F. (Francesco), Demerath, E.W. (Ellen), Dunning, A.M. (Alison), Gandin, I. (Ilaria), Grove, M.L. (Megan L.), Gudbjartsson, D.F. (Daniel), Hocking, L.J. (Lynne), Hofman, A. (Albert), Huang, J. (Jian), Jackson, R.D. (Rebecca), Karasik, D. (David), Kriebel, J. (Jennifer), Lange, E.M. (Ethan), Lange, L.A. (Leslie), Langenberg, C. (Claudia), Li, X. (Xin), Luan, J., Mägi, R. (Reedik), Morrison, A.C. (Alanna), Padmanabhan, S. (Sandosh), Pirie, A. (Ailith), Polasek, O. (Ozren), Porteous, D.J. (David J.), Reiner, A. (Alexander), Rivadeneira Ramirez, F. (Fernando), Rudan, I. (Igor), Sala, C. (Cinzia), Schlessinger, D. (David), Scott, R.A. (Robert), Stöckl, D. (Doris), Visser, J.A. (Jenny), Völker, U. (Uwe), Vozzi, D. (Diego), Wilson, J.G. (James), Zygmunt, M. (Marek), Boerwinkle, E.A. (Eric), Buring, J.E. (Julie), Crisponi, L. (Laura), Easton, D.F. (Douglas), Hayward, C. (Caroline), Hu, F.B. (Frank), Liu, S. (Simin), Metspalu, A. (Andres), Pennell, C.E. (Craig), Ridker, P.M. (Paul), Strauch, K. (Konstantin), Streeten, E.A. (Elizabeth), Toniolo, D. (Daniela), Uitterlinden, A.G. (André), Ulivi, S. (Shelia), Völzke, H. (Henry), Wareham, N.J. (Nick), Wellons, M. (Melissa), Franceschini, N. (Nora), Chasman, D.I. (Daniel), Thorsteinsdottir, U. (Unnur), Murray, A. (Anna), Zwart, J-A. (John-Anker), Murabito, J. (Joanne), Ong, K.K. (Ken), Perry, J.R.B. (John), Forouhi, N.G. (Nita G.), Kerrison, N.D. (Nicola D.), Sharp, S.J. (Stephen J.), Sims, M.A. (Matthew), Barroso, I.E. (Inês), Deloukas, P. (Panagiotis), McCarthy, M.I. (Mark), Arriola, L. (Larraitz), Balkau, B. (Beverley), Barricarte, A. (Aurelio), Boeing, H. (Heiner), Franks, P.W., Gonzalez, C. (Carlos), Grioni, S. (Sara), Kaaks, R. (Rudolf), Key, T.J. (Timothy J.), Navarro, C. (Carmen), Nilsson, P.M. (Peter M.), Overvad, K. (Kim), Palli, D. (Domenico), Panico, S. (Salvatore), Quirós, J.R., Rolandsson, O. (Olov), Sacerdote, C. (Carlotta), Sánchez, M.-J. (María-José), Slimani, N. (Nadia), Tjonneland, A. (Anne), Tumino, R. (Rosario), Van Der A, D.L. (Daphne L.), Schouw, Y.T. (Yvonne) van der, Riboli, E. (Elio), Smith, B.H. (Blair), Campbell, A. (Archie), Deary, I.J. (Ian), McIntosh, A.M. (Andrew), Lunetta, K.L. (Kathryn), Day, F.R. (Felix), Sulem, P. (Patrick), Ruth, K.S. (Katherine S.), Tung, J.Y. (Joyce Y.), Hinds, D.A. (David A.), Esko, T. (Tõnu), Elks, C.E. (Cathy), Altmaier, E.L. (Elizabeth), He, C. (Chunyan), Huffman, J.E. (Jennifer), Mihailov, E. (Evelin), Porcu, E. (Eleonora), Robino, A. (Antonietta), Rose, L.M. (Lynda), Schick, U.M. (Ursula), Stolk, L. (Lisette), Teumer, A. (Alexander), Thompson, D. (Deborah), Traglia, M. (Michela), Wang, C.A. (Carol A.), Yerges-Armstrong, L.M. (Laura), Antoniou, A.C. (Antonis), Barbieri, C. (Caterina), Coviello, A.D. (Andrea), Cucca, F. (Francesco), Demerath, E.W. (Ellen), Dunning, A.M. (Alison), Gandin, I. (Ilaria), Grove, M.L. (Megan L.), Gudbjartsson, D.F. (Daniel), Hocking, L.J. (Lynne), Hofman, A. (Albert), Huang, J. (Jian), Jackson, R.D. (Rebecca), Karasik, D. (David), Kriebel, J. (Jennifer), Lange, E.M. (Ethan), Lange, L.A. (Leslie), Langenberg, C. (Claudia), Li, X. (Xin), Luan, J., Mägi, R. (Reedik), Morrison, A.C. (Alanna), Padmanabhan, S. (Sandosh), Pirie, A. (Ailith), Polasek, O. (Ozren), Porteous, D.J. (David J.), Reiner, A. (Alexander), Rivadeneira Ramirez, F. (Fernando), Rudan, I. (Igor), Sala, C. (Cinzia), Schlessinger, D. (David), Scott, R.A. (Robert), Stöckl, D. (Doris), Visser, J.A. (Jenny), Völker, U. (Uwe), Vozzi, D. (Diego), Wilson, J.G. (James), Zygmunt, M. (Marek), Boerwinkle, E.A. (Eric), Buring, J.E. (Julie), Crisponi, L. (Laura), Easton, D.F. (Douglas), Hayward, C. (Caroline), Hu, F.B. (Frank), Liu, S. (Simin), Metspalu, A. (Andres), Pennell, C.E. (Craig), Ridker, P.M. (Paul), Strauch, K. (Konstantin), Streeten, E.A. (Elizabeth), Toniolo, D. (Daniela), Uitterlinden, A.G. (André), Ulivi, S. (Shelia), Völzke, H. (Henry), Wareham, N.J. (Nick), Wellons, M. (Melissa), Franceschini, N. (Nora), Chasman, D.I. (Daniel), Thorsteinsdottir, U. (Unnur), Murray, A. (Anna), Zwart, J-A. (John-Anker), Murabito, J. (Joanne), Ong, K.K. (Ken), Perry, J.R.B. (John), Forouhi, N.G. (Nita G.), Kerrison, N.D. (Nicola D.), Sharp, S.J. (Stephen J.), Sims, M.A. (Matthew), Barroso, I.E. (Inês), Deloukas, P. (Panagiotis), McCarthy, M.I. (Mark), Arriola, L. (Larraitz), Balkau, B. (Beverley), Barricarte, A. (Aurelio), Boeing, H. (Heiner), Franks, P.W., Gonzalez, C. (Carlos), Grioni, S. (Sara), Kaaks, R. (Rudolf), Key, T.J. (Timothy J.), Navarro, C. (Carmen), Nilsson, P.M. (Peter M.), Overvad, K. (Kim), Palli, D. (Domenico), Panico, S. (Salvatore), Quirós, J.R., Rolandsson, O. (Olov), Sacerdote, C. (Carlotta), Sánchez, M.-J. (María-José), Slimani, N. (Nadia), Tjonneland, A. (Anne), Tumino, R. (Rosario), Van Der A, D.L. (Daphne L.), Schouw, Y.T. (Yvonne) van der, Riboli, E. (Elio), Smith, B.H. (Blair), Campbell, A. (Archie), Deary, I.J. (Ian), and McIntosh, A.M. (Andrew)

Abstract

More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only ∼ 3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency protein-coding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P<5 × 10-8). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P=9.4 × 10-13) and FAAH2 (rs5914101, P=4.9 × 10-10). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P=2.8 × 10-11), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain ∼0.5% variance, indicating that these overlooked sources of variation do not substantially explain the 'missing heritability' of this complex trait.

Published
2015
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results