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202. Joint effects of fatty acid desaturase 1 polymorphisms and dietary polyunsaturated fatty acid intake on circulating fatty acid proportions.

Author

Juan, Juan, Huang, Hongyan, Jiang, Xia, Korat, Andres V Ardisson, Song, Mingyang, Sun, Qi, Willett, Walter C, Jensen, Majken K, and Kraft, Peter

Subjects
ALLELES, CONFIDENCE intervals, FAT content of food, GENETIC polymorphisms, INGESTION, MEDICAL personnel, NUTRITIONAL assessment, PROBABILITY theory, QUESTIONNAIRES, REGRESSION analysis, STATISTICAL hypothesis testing, STATISTICS, T-test (Statistics), UNSATURATED fatty acids, DOCOSAHEXAENOIC acid, EICOSAPENTAENOIC acid, DATA analysis, CASE-control method, DATA analysis software, DESCRIPTIVE statistics, ODDS ratio, GENOTYPES
Abstract

Background: Polyunsaturated fatty acids (PUFAs) are associated with a lower risk of multiple diseases. Fatty acid desaturase 1 gene (FADSl) polymorphisms and dietary PUFA intake are both established determinants of circulating PUFA proportions. Objective: We explored the joint effects of FADSl polymorphisms and dietary PUFA intake on circulating PUFA proportions. Design: We studied 2288 participants from a nested case-control study of coronary artery disease among participants who provided blood samples in the Nurses' Health Study and the Health Professionals Follow-Up Study. Dietary PUFA intake was obtained from semiquantitative food-frequency questionnaires. FADSl rs174546 was genotyped by using the Affymetrix 6.0 platform, and circulating PUFA proportions were measured with gas-liquid chromatography. Linear regression models were used to examine the associations between rs174546 and circulating proportions of each fatty acid. Gene-diet interactions were tested by including a cross-product term of dietary intake of each PUFA by rs174546 genotype in the linear regression models. Results: After adjustment for sex and ancestry, each copy of the C allele of rs174546 was associated with higher circulating pro-portions of arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) and lower proportions of linoleic acid and a-linolenic acid. The magnitude of positive association between higher consumption of dietary EPA or DHA and circulating pro-portions of EPA increased with each copy of the rs174546_T allele (P-interaction = 0.01 and 0.007, respectively). Each 1-SD increment in EPA intake was associated with an average 3.7% increase in circulating EPA proportions among participants with the rs174546_CC genotype and an average 7.8% increase among participants with the TT genotype. Conclusions: Carriers of the T allele at FADSl rs174546 may need higher doses of dietary EPA and DHA to achieve the same circulating proportions of EPA as carriers of the C allele. The implications of these findings on disease risk and dietary guidelines require further study. [ABSTRACT FROM AUTHOR]

Published
2018
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203. High density lipoprotein and its apolipoprotein-defined subspecies and risk of dementia

Author

Koch, Manja, DeKosky, Steven T., Goodman, Matthew, Sun, Jiehuan, Furtado, Jeremy D., Fitzpatrick, Annette L., Mackey, Rachel H., Cai, Tianxi, Lopez, Oscar L., Kuller, Lewis H., Mukamal, Kenneth J., and Jensen, Majken K.

Abstract

Whether HDL is associated with dementia risk is unclear. In addition to apoA1, other apolipoproteins are found in HDL, creating subspecies of HDL that may have distinct metabolic properties. We measured apoA1, apoC3, and apoJ levels in plasma and apoA1 levels in HDL that contains or lacks apoE, apoJ, or apoC3 using a modified sandwich ELISA in a case-cohort study nested within the Ginkgo Evaluation of Memory Study. We included 995 randomly selected participants and 521 participants who developed dementia during a mean of 5.1 years of follow-up. The level of total apoA1 was not significantly related to dementia risk, regardless of the coexistence of apoC3, apoJ, or apoE. Higher levels of total plasma apoC3 were associated with better cognitive function at baseline (difference in Modified Mini-Mental State Examination scores tertile 3 vs. tertile 1: 0.60; 95% CI: 0.23, 0.98) and a lower dementia risk (adjusted hazard ratio tertile 3 vs. tertile 1: 0.73; 95% CI: 0.55, 0.96). Plasma concentrations of apoA1 in HDL and its apolipoprotein-defined subspecies were not associated with cognitive function at baseline or with the risk of dementia during follow-up. Similar studies in other populations are required to better understand the association between apoC3 and Alzheimer's disease pathology.

Published
2020
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204. Proceedings from the Albert Charitable Trust Inaugural Workshop on white matter and cognition in aging

Author

Sorond, Farzaneh A., Whitehead, Shawn, Arai, Ken, Arnold, Douglas, Carmichael, S. Thomas, De Carli, Charles, Duering, Marco, Fornage, Myriam, Flores-Obando, Rafael E., Graff-Radford, Jonathan, Hamel, Edith, Hess, David C., Ihara, Massafumi, Jensen, Majken K., Markus, Hugh S., Montagne, Axel, Rosenberg, Gary, Shih, Andy Y., Smith, Eric E., Thiel, Alex, Tse, Kai Hei, Wilcock, Donna, and Barone, Frank

Abstract

This third in a series of vascular cognitive impairment (VCI) workshops, supported by “The Leo and Anne Albert Charitable Trust,” was held from February 8 to 12 at the Omni Resort in Carlsbad, CA. This workshop followed the information gathered from the earlier two workshops suggesting that we focus more specifically on brain white matter in age-related cognitive impairment. The Scientific Program Committee (Frank Barone, Shawn Whitehead, Eric Smith, and Rod Corriveau) assembled translational, clinical, and basic scientists with unique expertise in acute and chronic white matter injury at the intersection of cerebrovascular and neurodegenerative etiologies. As in previous Albert Trust workshops, invited participants addressed key topics related to mechanisms of white matter injury, biomarkers of white matter injury, and interventions to prevent white matter injury and age-related cognitive decline. This report provides a synopsis of the presentations and discussions by the participants, including the existing knowledge gaps and the delineation of the next steps towards advancing our understanding of white matter injury and age-related cognitive decline. Workshop discussions and consensus resulted in action by The Albert Trust to (1) increase support from biannual to annual “White Matter and Cognition” workshops; (2) provide funding for two collaborative, novel research grants annually submitted by meeting participants; and (3) coordinate the formation of the “Albert Research Institute for White Matter and Cognition.” This institute will fill a gap in white matter science, providing white matter and cognition communications, including annual updates from workshops and the literature and interconnecting with other Albert Trust scientific endeavors in cognition and dementia, and providing support for newly established collaborations between seasoned investigators and to the development of talented young investigators in the VCI-dementia (VCID) and white matter cognition arena.

Published
2020
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205. Cholesterol efflux capacity, HDL cholesterol, and risk of coronary heart disease: a nested case-control study in men

Author

Cahill, Leah E., Sacks, Frank M., Rimm, Eric B., and Jensen, Majken K.

Abstract

The capacity of HDLs to accept cholesterol effluxing from macrophages has been proposed as a new biomarker of HDLs' anti-atherogenic function. Whether cholesterol efflux capacity (CEC) is independent of HDL cholesterol (HDL-C) as a biomarker for coronary heart disease (CHD) risk in a generally healthy primary-prevention population remains unanswered. Therefore, in this nested case-control study, we simultaneously assessed CEC (using J774 cells) and plasma HDL-C levels as predictors of CHD in healthy middle-aged and older men not receiving treatment affecting blood lipid concentrations. We used risk-set sampling of participants free of disease at baseline from the Health Professionals Follow-Up Study, and matched cases (n = 701) to controls 1:1 for age, smoking, and blood sampling date. We applied conditional logistic regression models to calculate the multivariable relative risk and 95% CIs of CHD over 16 years of follow-up. CEC and HDL-C were correlated (r= 0.50, P< 0.0001). The risk (95% CI) of CHD per one SD higher CEC was 0.82 (0.71–0.96), but completely attenuated to 1.08 (0.85–1.37) with HDL-C in the model. The association per one SD between HDL-C and CHD (0.66; 0.58–0.76) was essentially unchanged (0.68; 0.53–0.88) after adjustment for CEC. These findings indicate that CEC's ability to predict CHD may not be independent of HDL-C in a cohort of generally healthy men.

Published
2019
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206. Gene × Physical Activity Interactions in Obesity: Combined Analysis of 111,421 Individuals of European Ancestry

Author

Pedersen, Nancy L., Langenberg, Claudia, Jensen, Majken K., Pasquale, Louis T., Sandholt, Camilla H., Koivula, Robert W., Rukh, Gull, Grarup, Niels, Shungin, Dmitry, Allin, Kristine H., Varga, Tibor V., Jørgensen, Torben, Ali, Ashfaq, Rose, Lynda M., Linneberg, Allan, Magnusson, Patrik K. E., Ahmad, Shafqat, Boehnke, Michael, Brage, Soren, Qi, Qibin, Curhan, Gary, Ericson, Ulrika, Tamimi, Rulla M., Paré, Guillaume, Kurbasic, Azra, Mohlke, Karen L., Ganna, Andrea, Hamsten, Anders, Stančáková, Alena, Elks, Cathy E., Chu, Audrey Y., and Aadahl, Mette

Abstract

Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age2, sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS × physical activity interaction effect estimate (Pinteraction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, Pinteraction = 0.014 vs. n = 71,611, Pinteraction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (Pinteraction = 0.003) and the SEC16B rs10913469 (Pinteraction = 0.025) variants showed evidence of SNP × physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.

Published
2013
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207. Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry. : combined analysis of 111,421 individuals of European ancestry

Author

Ahmad, Shafqat, Rukh, Gull, V Varga, Tibor, Ali, Ashfaq, Kurbasic, Azra, Shungin, Dmitry, Ericson, Ulrika, Koivula, Robert, Chu, Audrey Y, Rose, Lynda M, Ganna, Andrea, Qi, Qibin, Stančáková, Alena, Sandholt, Camilla H, Elks, Cathy E, Curhan, Gary, Jensen, Majken K, Tamimi, Rulla M, Allin, Kristine H, Jørgensen, Torben, Brage, Soren, Langenberg, Claudia, Aadahl, Mette, Grarup, Niels, Linneberg, Allan, Paré, Guillaume, Magnusson, Patrik K E, Pedersen, Nancy L, Boehnke, Michael, Hamsten, Anders, Mohlke, Karen L, Pasquale, Louis T, Pedersen, Oluf, Scott, Robert A, Ridker, Paul M, Ingelsson, Erik, Laakso, Markku, Hansen, Torben, Qi, Lu, Wareham, Nicholas J, Chasman, Daniel I, Hallmans, Göran, Hu, Frank B, Renström, Frida, Orho-Melander, Marju, and Franks, Paul

Subjects
Adult, Male, Motor Activity/genetics, Endocrinology and Diabetes, Obesity/epidemiology, Polymorphism, Single Nucleotide, Body Mass Index, Logistic Models, Risk Factors, Surveys and Questionnaires, Humans, Female, Genetic Predisposition to Disease, European Continental Ancestry Group/genetics, Alleles, Genetic Association Studies
Abstract

Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS × physical activity interaction effect estimate (Pinteraction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, Pinteraction = 0.014 vs. n = 71,611, Pinteraction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (Pinteraction = 0.003) and the SEC16B rs10913469 (Pinteraction = 0.025) variants showed evidence of SNP × physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.

Published
2013

209. Societal costs and survival of patients with biopsy-verified non-alcoholic steatohepatitis: Danish nationwide register-based study

Author

Rudolfsen, Jan Håkon, Gluud, Lise Lotte, Grønbæk, Henning, Jensen, Majken K., Vyberg, Mogens, Olsen, Jens, Bo Poulsen, Peter, Hovelsø, Nanna, Gregersen, Nikolaj Ture, Thomsen, Anne Bloch, and Jepsen, Peter

Abstract

Studies on the societal burden of patients with biopsy-confirmed non-alcoholic fatty liver disease (NAFLD) are sparse. This study examined this question, comparing NAFLD with matched reference groups.

Published
2024
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210. Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium

Author

Dehghan, Abbas, primary, Bis, Joshua C., additional, White, Charles C., additional, Smith, Albert Vernon, additional, Morrison, Alanna C., additional, Cupples, L. Adrienne, additional, Trompet, Stella, additional, Chasman, Daniel I., additional, Lumley, Thomas, additional, Völker, Uwe, additional, Buckley, Brendan M., additional, Ding, Jingzhong, additional, Jensen, Majken K., additional, Folsom, Aaron R., additional, Kritchevsky, Stephen B., additional, Girman, Cynthia J., additional, Ford, Ian, additional, Dörr, Marcus, additional, Salomaa, Veikko, additional, Uitterlinden, André G., additional, Eiriksdottir, Gudny, additional, Vasan, Ramachandran S., additional, Franceschini, Nora, additional, Carty, Cara L., additional, Virtamo, Jarmo, additional, Demissie, Serkalem, additional, Amouyel, Philippe, additional, Arveiler, Dominique, additional, Heckbert, Susan R., additional, Ferrières, Jean, additional, Ducimetière, Pierre, additional, Smith, Nicholas L., additional, Wang, Ying A., additional, Siscovick, David S., additional, Rice, Kenneth M., additional, Wiklund, Per-Gunnar, additional, Taylor, Kent D., additional, Evans, Alun, additional, Kee, Frank, additional, Rotter, Jerome I., additional, Karvanen, Juha, additional, Kuulasmaa, Kari, additional, Heiss, Gerardo, additional, Kraft, Peter, additional, Launer, Lenore J., additional, Hofman, Albert, additional, Markus, Marcello R. P., additional, Rose, Lynda M., additional, Silander, Kaisa, additional, Wagner, Peter, additional, Benjamin, Emelia J., additional, Lohman, Kurt, additional, Stott, David J., additional, Rivadeneira, Fernando, additional, Harris, Tamara B., additional, Levy, Daniel, additional, Liu, Yongmei, additional, Rimm, Eric B., additional, Jukema, J. Wouter, additional, Völzke, Henry, additional, Ridker, Paul M., additional, Blankenberg, Stefan, additional, Franco, Oscar H., additional, Gudnason, Vilmundur, additional, Psaty, Bruce M., additional, Boerwinkle, Eric, additional, and O'Donnell, Christopher J., additional

Published
2016
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213. Multilocus Heterozygosity and Coronary Heart Disease: Nested Case-Control Studies in Men and Women

Author

Mukamal, Kenneth J., Jensen, Majken K., Pers, Tune Hannes, Pai, Jennifer K., Kraft, Peter, Rimm, Eric B., Mukamal, Kenneth J., Jensen, Majken K., Pers, Tune Hannes, Pai, Jennifer K., Kraft, Peter, and Rimm, Eric B.

Abstract

Background: Generalized allelic heterozygosity has been proposed to improve reproductive fitness and has been associated with higher blood pressure, but its association with chronic disease is not well characterized. Methods: Using the Affymetrix Genome-Wide Human 6.0 array, we performed whole genome scans in parallel case-control studies of coronary heart disease (CHD) nested in the Health Professionals Follow-up Study and Nurses' Health Study. We examined ∼ 700,000 single nucleotide polymorphisms (SNPs) in 435 men with incident CHD and 878 matched controls and 435 women with incident CHD with 931 matched controls. We examined the relationship of genome-wide heterozygosity with risk of incident of CHD and with baseline levels of cardiovascular risk factors. Results: In both cohorts, approximately 227650 (SD 2000) SNPs were heterozygous. The number of heterozygous SNPs was not related to risk of CHD in either men or women (adjusted odds ratios per 2000 heterozygous SNPs 1.01 [95% confidence interval, 0.91-1.13] in women and 0.94 [0.84-1.06] in men). We also found no consistent associations of genome-wide heterozygosity with levels of lipids, inflammatory markers, adhesion molecules, homocysteine, adiponectin, or body-mass index. Conclusions: In these parallel nested case-control studies, we found no relationship of multilocus heterozygosity with risk of CHD or its major risk factors. Studies in other populations are needed to rule out associations with lower levels of heterozygosity.

Published
2015

214. Fetuin-A and risk of coronary heart disease: A Mendelian randomization analysis and a pooled analysis of AHSG genetic variants in 7 prospective studies

Author

Laugsand, Lars E., primary, Ix, Joachim H., additional, Bartz, Traci M., additional, Djousse, Luc, additional, Kizer, Jorge R., additional, Tracy, Russell P., additional, Dehghan, Abbas, additional, Rexrode, Kathryn, additional, Lopez, Oscar L., additional, Rimm, Eric B., additional, Siscovick, David S., additional, O'Donnell, Christopher J., additional, Newman, Anne, additional, Mukamal, Kenneth J., additional, and Jensen, Majken K., additional

Published
2015
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215. Urinary uromodulin, kidney function, and cardiovascular disease in elderly adults

Author

Garimella, Pranav S., primary, Biggs, Mary L., additional, Katz, Ronit, additional, Ix, Joachim H., additional, Bennett, Michael R., additional, Devarajan, Prasad, additional, Kestenbaum, Bryan R., additional, Siscovick, David S., additional, Jensen, Majken K., additional, Shlipak, Michael G., additional, Chaves, Paulo H.M., additional, and Sarnak, Mark J., additional

Published
2015
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219. A prospective analysis of the association between dietary fiber intake and prostate cancer risk in EPIC

Author

Suzuki, Reiko Allen, Naomi E. Key, Timothy J. Appleby, Paul N. Tjonneland, Anne Johnsenz, Nina Fons Jensen, Majken K. and Overvad, Kim Boeing, Heiner Pischon, Tobias Kaaks, Rudolf Rohrmann, Sabine Trichopoulou, Antonia Misirli, Gesthimani Trichopoulos, Dimitrios Bueno-de-Mesquita, H. Bas and van Duijnhoven, Franzel Sacerdote, Carlotta Pala, Valeria and Palli, Domenico Tumino, Rosario Ardanaz, Eva Quiros, Jose Ramon Larranaga, Nerea Sanchez, Maria-Jose Tormo, Maria-Jose and Jakszyn, Paula Johansson, Ingegerd Stattin, Par and Berglund, Goran Manjer, Jonas Bingham, Sheila Khaw, Kay-Tee and Egevad, Lars Ferrari, Pietro Jenab, Mazda Riboli, Elio

Abstract

Few studies have examined the association between dietary fiber intake and prostate cancer risk. We evaluated the association between dietary fiber intake and the risk of prostate cancer among 142,590 men in the European Prospective Investigation into Cancer and Nutrition (EPIC). Consumption of dietary fiber (total, cereal, fruit and vegetable fiber) seas estimated by validated dietary questionnaires and calibrated using 24-hr dietary recalls. Incidence rate ratios were estimated using Cox regression and adjusted for potential confounding factors. During all average of 8.7 years follow-up, prostate cancer was diagnosed in 2,747 men. Overall, there was no association between dietary fiber intake (total, cereal, fruit or vegetable fiber) and prostate cancer risk, although calibrated intakes of total fiber and fruit fiber were associated with nonstatistically significant reductions in risk. There was no association between fiber derived from cereals or vegetables and risk and no evidence for heterogeneity in any of the risk estimates by stage or grade of disease. Our results suggest that dietary fiber intake is not associated with prostate cancer risk. (C) 2008 Wiley-Liss, Inc.

Published
2009

220. CDH1 gene polymorphisms, smoking, Helicobacter pylori infection and the risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST)

Author

Jenab, Mazda McKay, James D. Ferrari, Pietro Biessy, Carine and Laing, Stewart Capella Munar, Gabriel Maria Sala, Nuria and Pena, Salvador Crusius, J. B. A. Overvad, Kim Jensen, Majken K. Olsen, Anja Tjonneland, Anne Clavel-Chapelon, Francoise and Boutron-Ruault, Marie-Christine Kaaks, Rudolf Linseisen, Jakob Boeing, Heiner Bergmann, Manuela M. Trichopoulou, Antonia Georgila, Christina Psaltopoulou, Theodora and Mattiello, Amalia Vineis, Paolo Pala, Valeria Palli, Domenico Tumino, Rosario Numans, Mattijs E. Peeters, Petra H. M. Bueno-de-Mesquita, H. Bas Lund, Eiliv Ardanaz, Eva and Sanchez, Maria-Jose Dorronsoro, Miren Navarro Sanchez, Carmen and Ramon Quiros, Jose Hallmans, Goran Stenling, Roger and Manjer, Jonas Regner, Sara Key, Tim Bingham, Sheila and Khaw, Kay-tee Slimani, Nadia Rinaldi, Sabina Boffetta, Paolo and Carneiro, Fatima Riboli, Elio Gonzalez, Carlos

Abstract

Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. E-Cadherin is an adhesion molecule that is thought to be involved in GC. Germline mutations in the E-Cadherin gene (CDH1) have been identified in hereditary diffuse GC. Also, a promoter polymorphism at position 160 C/A has been suggested to lead to transcriptional down regulation and has been shown to affect GC risk in some studies. However, very little information exists on the GC risk association of other CDH1 polymorphisms and it is unclear whether any associations may be different by GC anatomical sites or histological types. Thus, a case-control study (cases = 245/controls = 950) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort was conducted to assess the GC risk association of eight CDH1 gene polymorphisms. None of the CDH1 polymorphisms or haplotypes analysed were associated with GC risk and no differences of effect were observed by Helicobacter pylori infection status. However, three CDH1 polymorphisms in the same haplotype block, including the CDH1-160C/A, interacted with smoking to increase GC risk in smokers but not in never smokers. These findings should be confirmed in larger independent studies. (c) 2008 Elsevier Ltd. All rights reserved.

Published
2008

221. Alcohol consumption and the risk for prostate cancer in the European prospective investigation into cancer and nutrition

Author

Rohrmann, Sabine Linseisen, Jakob Key, Timothy J. Jensen, Majken K. Overvad, Kim Johnsen, Nina Fons Tjonneland, Anne and Kaaks, Rudolf Bergmann, Manuela M. Weikert, Cornelia and Naska, Androniki Trichopoulou, Antonia Trichopoulos, Dimitrios and Pala, Valeria Sacerdote, Carlotta Palli, Domenico and Tumino, Rosario Bueno-de-Mesquita, H. Bas Vrieling, Alina and Gonzalez, Carlos A. Larranaga, Nerea Navarro, Carmen and Barricarte, Aurelio Quiros, J. Ramon Martinez-Garcia, Carmen and Hallmans, Goeran Stattin, Paer Manjer, Jonas Wirfalt, Elisabet Bingham, Sheila Khaw, Key-Tee Egevad, Lars and Ferrari, Pietro Jenab, Mazda Riboli, Elio

Abstract

Alcohol is a risk factor for several types of cancer. However, the results for prostate cancer have been inconsistent, with most studies showing no association. Within the European Prospective Investigation into Cancer and Nutrition, detailed information were collected from 142,607 male participants on the intake of alcoholic beverages at recruitment (for 100% of the cohort) and over lifetime (for 76% of the cohort) between 1992 and 2000. During a median follow-up of 8.7 years, 2,655 prostate cancer cases were observed. Multivariate Cox proportional hazard models were used to examine the association of alcohol consumption at recruitment and average lifetime alcohol consumption with prostate cancer adjusted for age, center, smoking, height, weight, physical activity, and nonalcohol energy intake. Overall, neither alcohol consumption at baseline nor average lifetime alcohol consumption was associated with the risk for prostate cancer in this cohort of men. Men who consumed >= 60 g alcohol per day had a relative risk of 0.88 [95% confidence interval (95% CI) 0.72-1.081 compared with men with an intake of 0.1-4.9 g/d; the respective relative risk for average lifetime intake was 1.09 (95% CI, 0.86-1.39). For advanced prostate cancer (n=537), the relative risks for >= 60 and 0.1-4.9 g alcohol per day at baseline were 0.98 (95% CI, 0.66-1.44) and 1.28 (95% CI, 0.79-2-07), respectively, for average lifetime intake. No statistically significant association was observed for alcohol intake from specific alcoholic beverages. Our results indicate no association between the consumption of alcohol and prostate cancer in this cohort of European men.

Published
2008

224. Ethanol intake and risk of lung cancer in the European prospective investigation into cancer and nutrition (EPIC)

Author

Rohrmann, Sabine Linseisen, Jakob Boshuizen, Hendriek C. and Whittaker, John Agudo, Antonio Vineis, Paolo Boffetta, Paolo and Jensen, Majken K. Olsen, Anja Overvad, Kim Tjonneland, Anne Boutron-Ruault, Marie-Christine Clavel-Chapelon, Francoise and Bergmann, Manuela M. Boeing, Heiner Allen, Naomi Key, Tim Bingham, Sheila Khaw, Kay-Tee Kyriazi, Georgia and Soukara, Stavroula Trichopoulou, Antonia Panico, Salvatore and Palli, Domenico Sieri, Sabina Tumino, Rosario Peeters, Petra H. M. Bueno-de-Mesquita, H. Bas Buchner, Frederike L. Gram, Inger Torhild Lund, Eiliv Ardanaz, Eva Chirlaque, Maria-Dolores Dorronsoro, Miren Sanchez Perez, Maria-Jose and Quiros, Jose R. Berglund, GorRan Janzon, Lars Rasmuson, Torgny Weinehall, Lars Ferrari, Pietro Jenab, Mazda and Norat, Teresa Riboli, Elio

Abstract

Within the European Prospective Investigation into Cancer and Nutrition (EPIC), the authors examined the association of ethanol intake at recruitment (1,119 cases) and mean lifelong ethanol intake (887 cases) with lung cancer. Information on baseline and past alcohol consumption, lifetime tobacco smoking, diet, and the anthropometric characteristics of 478,590 participants was collected between 1992 and 2000. Cox proportional hazards regression was used to calculate multivariate-adjusted hazard ratios and 95% confidence intervals. Overall, neither ethanol intake at recruitment nor mean lifelong ethanol intake was significantly associated with lung cancer. However, moderate intake (5-14.9 g/day) at recruitment (hazard ratio (HR) = 0.76, 95% confidence interval (CI): 0.63, 0.90) and moderate mean lifelong intake (HR = 0.80, 95% CI: 0.66, 0.97) were associated with a lower lung cancer risk in comparison with low consumption (0.1-4.9 g/day). Compared with low intake, a high (>= 60 g/day) mean lifelong ethanol intake tended to be related to a higher risk of lung cancer (HR = 1.29, 95% CI: 0.93, 1.74), but high intake at recruitment was not. Although there was no overall association between ethanol intake and risk of lung cancer, the authors cannot rule out a lower risk for moderate consumption and a possibly increased risk for high lifelong consumption.

Published
2006

225. High-Density Lipoprotein Subspecies Defined by Presence of Apolipoprotein C-III and Incident Coronary Heart Disease in Four Cohorts.

Author

Jensen, Majken K., Aroner, Sarah A., Mukamal, Kenneth J., Furtado, Jeremy D., Post, Wendy S., Tsai, Michael Y., Tjønneland, Anne, Polak, Joseph F., Rimm, Eric B., Overvad, Kim, McClelland, Robyn L., and Sacks, Frank M.

Subjects
*HIGH density lipoproteins, *APOLIPOPROTEINS, *CORONARY disease, *IMMUNOAFFINITY chromatography, *META-analysis
Abstract

BACKGROUND: The causal role of high-density lipoprotein (HDL) cholesterol in cardioprotection has been questioned by genetic and randomized studies. Novel measures that relate to HDL function may contribute new information to the prediction of cardiovascular risk. Apolipoprotein C-III (apoC-III) is a key regulator of lipoprotein metabolism. We investigated whether subspecies of HDL defined by apoC-III are associated with coronary heart disease (CHD). METHODS: We used immunoaffinity chromatography to measure the apoA-I concentrations of HDL that contains and lacks apoC-III in 2 prospective studies of adults free of CHD. In MESA (Multi-Ethnic Study of Atherosclerosis), 5657 participants (52% women, 52-72 years of age) were followed for risk of CHD from 2000 to 2002 through 2013. In a case-cohort study nested within the DCH study (Danish Diet, Cancer, and Health), 3642 participants (47% women, 51-64 years of age) were followed from 1994 to 1997 through 2010. Subsequently, we conducted a meta-analysis that combined these results with the previously published findings from 2 cohort studies that used similar laboratory methodology to measure lipoproteins, totaling 2997 incident cases. RESULTS: ApoC-III was found on 6% to 8% of apoA-I. The 2 HDL subspecies showed opposing associations, with risk of CHD in each of the individual cohorts and in the meta-analysis (P heterogeneity between the 2 subspecies <0.01). HDL that contains apoC-III was associated with a higher risk of CHD (pooled relative risk per standard deviation, 1.09; 95% confidence interval, 1.01-1.18), whereas HDL that lacks apoCIII was associated with lower risk (relative risk, 0.76; 95% confidence interval, 0.70-0.83). The relative risk for HDL lacking apoC-III was even more negative than the relative risk for total HDL (relative risk, 0.80; 95% confidence interval, 0.74-0.87). CONCLUSIONS: Our findings from 4 prospective studies support the hypothesis that apoC-III may mark a subfraction of HDL that is associated with higher risk of CHD. New measures reflecting HDL structure and function may provide novel insights for cardiovascular risk that extend beyond traditional plasma HDL cholesterol concentrations. [ABSTRACT FROM AUTHOR]

Published
2018
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227. Genetic Susceptibility, Change in Physical Activity, and Long-term Weight Gain.

Author

Tiange Wang, Tao Huang, Yoriko Heianza, Dianjianyi Sun, Yan Zheng, Wenjie Ma, Jensen, Majken K., Kang, Jae H., Wiggs, Janey L., Pasquale, Louis R., Rimm, Eric B., Manson, JoAnn E., Hu, Frank B., Willett, Walter C., Lu Qi, Wang, Tiange, Huang, Tao, Heianza, Yoriko, Sun, Dianjianyi, and Zheng, Yan

Subjects
PHYSICAL activity, WEIGHT gain, BODY mass index, SINGLE nucleotide polymorphisms, FAT, BODY composition, GENETICS, BODY weight, DISEASE susceptibility, EXERCISE, LONGITUDINAL method, RESEARCH funding
Abstract

Whether change in physical activity over time modifies the genetic susceptibility to long-term weight gain is unknown. We calculated a BMI-genetic risk score (GRS) based on 77 BMI-associated single nucleotide polymorphisms (SNPs) and a body fat percentage (BF%)-GRS based on 12 BF%-associated SNPs in 9,390 women from the Nurses' Health Study (NHS) and 5,291 men from the Health Professionals Follow-Up Study (HPFS). We analyzed the interactions between each GRS and change in physical activity on BMI/body weight change within five 4-year intervals from 1986 to 2006 using multivariable generalized linear models with repeated-measures analyses. Both the BMI-GRS and the BF%-GRS were associated with long-term increases in BMI/weight, and change in physical activity consistently interacted with the BF%-GRS on BMI change in the NHS (P for interaction = 0.025) and HPFS (P for interaction = 0.001). In the combined cohorts, 4-year BMI change per 10-risk allele increment was -0.02 kg/m2 among participants with greatest increase in physical activity and 0.24 kg/m2 among those with greatest decrease in physical activity (P for interaction < 0.001), corresponding to 0.01 kg versus 0.63 kg weight changes every 4 years (P for interaction = 0.001). Similar but marginal interactions were observed for the BMI-GRS (P for interaction = 0.045). Our data indicate that the genetic susceptibility to weight gain may be diminished by increasing physical activity. [ABSTRACT FROM AUTHOR]

Published
2017
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228. Apolipoprotein C-III and High-Density Lipoprotein Subspecies Defined by Apolipoprotein C-III in Relation to Diabetes Risk.

Author

Aroner, Sarah A., Ming Yang, Junlong Li, Furtado, Jeremy D., Sacks, Frank M., Tjønneland, Anne, Overvad, Kim, Tianxi Cai, and Jensen, Majken K.

Subjects
DIABETES risk factors, APOLIPOPROTEINS, BIOMARKERS, CONFIDENCE intervals, DIABETES, HIGH density lipoproteins, PROBABILITY theory, RISK assessment, PROPORTIONAL hazards models, DESCRIPTIVE statistics
Abstract

Apolipoprotein C-III (apoC-III) is a potential novel biomarker that may play an important role in the pathogenesis of diabetes, particularly when present on high-density lipoprotein (HDL). In a case-cohort design among 3,101 non-cases and 434 incident diabetes cases occurring before 2007 in the Danish Diet, Cancer, and Health study, we examined associations of baseline (1993-1997) plasma concentrations of apoC-III and subspecies of HDL defined by the presence or absence of apoC-III with risk of diabetes using Cox regression. ApoC-III was strongly associated with risk of diabetes (hazard ratio [HR], top vs. bottom quintile = 3.43; 95% CI: 1.75, 6.70; P-trend < 0.001). The cholesterol concentration of HDL (HDL-C) without apoC-III was inversely associated with risk of diabetes (HR = 0.48; 95% CI: 0.27, 0.85; P-trend = 0.002), more so than total HDL-C (HR = 0.60; 95% CI: 0.35, 1.03; P-trend = 0.04), whereas HDL-C with apoC-III was not associated (HR = 1.05; 95% CI: 0.50, 2.21; P-trend = 0.44) (P-heterogeneity, HDL-C with and without apoC-III = 0.002). ApoC-III itself is a strong risk marker for diabetes, and its presence on HDL may impair the anti-diabetogenic properties of HDL. ApoC-III has potential to be a therapeutic target for the prevention of diabetes. [ABSTRACT FROM AUTHOR]

Published
2017
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229. Detection of genetic loci associated with plasma fetuin-A: a meta-analysis of genome-wide association studies from the CHARGE Consortium.

Author

Jensen, Majken K., Jensen, Richard A., Mukamal, Kenneth J., Xiuqing Guo, Jie Yao, Qi Sun, Marilyn Cornelis, Yongmei Liu, Ming-Huei Chen, Kizer, Jorge R., Luc Djoussé, Siscovick, David S., Psaty, Bruce M., Zmuda, Joseph M., Rotter, Jerome I., Garcia, Melissa, Harris, Tamara, Ida Chen, Goodarzi, Mark O., and Nalls, Michael A.

Published
2017
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230. Habitual coffee consumption and genetic predisposition to obesity: gene-diet interaction analyses in three US prospective studies.

Author

Tiange Wang, Tao Huang, Kang, Jae H., Yan Zheng, Jensen, Majken K., Wiggs, Janey L., Pasquale, Louis R., Fuchs, Charles S., Campos, Hannia, Rimm, Eric B., Willett, Walter C., Hu, Frank B., Lu Qi, Wang, Tiange, Huang, Tao, Zheng, Yan, and Qi, Lu

Subjects
PHYSIOLOGICAL effects of coffee, OVERWEIGHT persons, PHYSIOLOGICAL effects of caffeine, BODY mass index, WOMEN'S health, HEALTH, PREVENTION of obesity, COFFEE, DIET, DISEASE susceptibility, LONGITUDINAL method, OBESITY, RESEARCH funding
Abstract

Background: Whether habitual coffee consumption interacts with the genetic predisposition to obesity in relation to body mass index (BMI) and obesity is unknown.Methods: We analyzed the interactions between genetic predisposition and habitual coffee consumption in relation to BMI and obesity risk in 5116 men from the Health Professionals Follow-up Study (HPFS), in 9841 women from the Nurses' Health Study (NHS), and in 5648 women from the Women's Health Initiative (WHI). The genetic risk score was calculated based on 77 BMI-associated loci. Coffee consumption was examined prospectively in relation to BMI.Results: The genetic association with BMI was attenuated among participants with higher consumption of coffee than among those with lower consumption in the HPFS (P interaction  = 0.023) and NHS (P interaction  = 0.039); similar results were replicated in the WHI (P interaction  = 0.044). In the combined data of all cohorts, differences in BMI per increment of 10-risk allele were 1.38 (standard error (SE), 0.28), 1.02 (SE, 0.10), and 0.95 (SE, 0.12) kg/m2 for coffee consumption of < 1, 1-3 and > 3 cup(s)/day, respectively (P interaction  < 0.001). Such interaction was partly due to slightly higher BMI with higher coffee consumption among participants at lower genetic risk and slightly lower BMI with higher coffee consumption among those at higher genetic risk. Each increment of 10-risk allele was associated with 78% (95% confidence interval (CI), 59-99%), 48% (95% CI, 36-62%), and 43% (95% CI, 28-59%) increased risk for obesity across these subgroups of coffee consumption (P interaction  = 0.008). From another perspective, differences in BMI per increment of 1 cup/day coffee consumption were 0.02 (SE, 0.09), -0.02 (SE, 0.04), and -0.14 (SE, 0.04) kg/m2 across tertiles of the genetic risk score.Conclusions: Higher coffee consumption might attenuate the genetic associations with BMI and obesity risk, and individuals with greater genetic predisposition to obesity appeared to have lower BMI associated with higher coffee consumption. [ABSTRACT FROM AUTHOR]

Published
2017
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231. Abstract MP45: Liver Fat Content Does Not Account for the Strong Association of Fetuin-A with Diabetes Risk in Women: The Multi-Ethnic Study of Atherosclerosis

Author

Aroner, Sarah A, primary, Mukamal, Kenneth J, additional, St-Jules, David E, additional, Budoff, Matthew J, additional, Katz, Ronit, additional, Criqui, Michael H, additional, Allison, Matthew A, additional, de Boer, Ian H, additional, Siscovick, David S, additional, Ix, Joachim H, additional, and Jensen, Majken K, additional

Published
2015
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232. Genetic loci associated with circulating phospholipid trans fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium

Author

Mozaffarian, Dariush, primary, Kabagambe, Edmond K, additional, Johnson, Catherine O, additional, Lemaitre, Rozenn N, additional, Manichaikul, Ani, additional, Sun, Qi, additional, Foy, Millennia, additional, Wang, Lu, additional, Wiener, Howard, additional, Irvin, Marguerite R, additional, Rich, Stephen S, additional, Wu, Hongyu, additional, Jensen, Majken K, additional, Chasman, Daniel I, additional, Chu, Audrey Y, additional, Fornage, Myriam, additional, Steffen, Lyn, additional, King, Irena B, additional, McKnight, Barbara, additional, Psaty, Bruce M, additional, Djoussé, Luc, additional, Chen, Ida Y-D, additional, Wu, Jason HY, additional, Siscovick, David S, additional, Ridker, Paul M, additional, Tsai, Michael Y, additional, Rimm, Eric B, additional, Hu, Frank B, additional, and Arnett, Donna K, additional

Published
2015
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233. En prospektiv undersøgelse af sammenhaengen mellem rygning og senere alkoholstorforbrug i den danske befolkning

Author

Jensen, Majken K, Sørensen, Thorkild I A, Andersen, Anne T, Thorsen, Thorkil, Tolstrup, Janne S, Godtfredsen, Nina S, and Grønbaek, Morten N

Subjects
Adult, Male, Questionnaires, genetic structures, Alcohol Drinking, Dose-Response Relationship, Drug, Denmark, Smoking, Middle Aged, eye diseases, Alcoholism, Risk Factors, Odds Ratio, Humans, Female, sense organs, Prospective Studies, Aged
Abstract

Udgivelsesdato: 2004-Oct-11

Published
2004

234. Genetic loci associated with circulating levels of very long-chain saturated fatty acids

Author

Lemaitre, Rozenn N., primary, King, Irena B., additional, Kabagambe, Edmond K., additional, Wu, Jason H.Y., additional, McKnight, Barbara, additional, Manichaikul, Ani, additional, Guan, Weihua, additional, Sun, Qi, additional, Chasman, Daniel I., additional, Foy, Millennia, additional, Wang, Lu, additional, Zhu, Jingwen, additional, Siscovick, David S., additional, Tsai, Michael Y., additional, Arnett, Donna K., additional, Psaty, Bruce M., additional, Djousse, Luc, additional, Chen, Yii-Der I., additional, Tang, Weihong, additional, Weng, Lu-Chen, additional, Wu, Hongyu, additional, Jensen, Majken K., additional, Chu, Audrey Y., additional, Jacobs, David R., additional, Rich, Stephen S., additional, Mozaffarian, Dariush, additional, Steffen, Lyn, additional, Rimm, Eric B., additional, Hu, Frank B., additional, Ridker, Paul M., additional, Fornage, Myriam, additional, and Friedlander, Yechiel, additional

Published
2015
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236. FTO genetic variants, dietary intake and body mass index:insights from 177 330 individuals

Author

Qi, Qibin, Oskari Kilpeläinen, Tuomas, Downer, Mary K, Tanaka, Toshiko, Smith, Caren E, Sluijs, Ivonne, Sonestedt, Emily, Chu, Audrey Y, Renström, Frida, Lin, Xiaochen, Angquist, Lars H, Huang, Jinyan, Liu, Zhonghua, Li, Yanping, Asif Ali, Muhammad, Xu, Min, Ahluwalia, Tarun Veer Singh, Boer, Jolanda M A, Chen, Peng, Daimon, Makoto, Eriksson, Johan, Perola, Markus, Friedlander, Yechiel, Gao, Yu-Tang, Heppe, Denise H M, Holloway, John W, Houston, Denise K, Kanoni, Stavroula, Kim, Yu-Mi, Laaksonen, Maarit A, Jääskeläinen, Tiina, Lee, Nanette R, Lehtimäki, Terho, Lemaitre, Rozenn N, Lu, Wei, Luben, Robert N, Manichaikul, Ani, Männistö, Satu, Marques-Vidal, Pedro, Monda, Keri L, Ngwa, Julius S, Perusse, Louis, van Rooij, Frank J A, Xiang, Yong-Bing, Wen, Wanqing, Wojczynski, Mary K, Zhu, Jingwen, Borecki, Ingrid B, Bouchard, Claude, Cai, Qiuyin, Cooper, Cyrus, Dedoussis, George V, Deloukas, Panos, Ferrucci, Luigi, Forouhi, Nita G, Hansen, Torben, Christiansen, Lene, Hofman, Albert, Johansson, Ingegerd, Jørgensen, Torben, Karasawa, Shigeru, Khaw, Kay-Tee, Kim, Mi-Kyung, Kristiansson, Kati, Li, Huaixing, Lin, Xu, Liu, Yongmei, Lohman, Kurt K, Long, Jirong, Mikkilä, Vera, Mozaffarian, Dariush, North, Kari, Pedersen, Oluf, Raitakari, Olli, Rissanen, Harri, Tuomilehto, Jaakko, van der Schouw, Yvonne T, Uitterlinden, André G, Carola Zillikens, M, Franco, Oscar H, Shyong Tai, E, Ou Shu, Xiao, Siscovick, David S, Toft, Ulla, Monique Verschuren, W M, Vollenweider, Peter, Wareham, Nicholas J, Witteman, Jacqueline C M, Zheng, Wei, Ridker, Paul M, Kang, Jae H, Liang, Liming, Jensen, Majken K, Curhan, Gary C, Pasquale, Louis R, Hunter, David J, Mohlke, Karen L, Uusitupa, Matti, Adrienne Cupples, L, Rankinen, Tuomo, Orho-Melander, Marju, Wang, Tao, Chasman, Daniel I, Franks, Paul W, Sørensen, Thorkild I A, Hu, Frank B, Loos, Ruth J F, Nettleton, Jennifer A, Qi, Lu, Qi, Qibin, Oskari Kilpeläinen, Tuomas, Downer, Mary K, Tanaka, Toshiko, Smith, Caren E, Sluijs, Ivonne, Sonestedt, Emily, Chu, Audrey Y, Renström, Frida, Lin, Xiaochen, Angquist, Lars H, Huang, Jinyan, Liu, Zhonghua, Li, Yanping, Asif Ali, Muhammad, Xu, Min, Ahluwalia, Tarun Veer Singh, Boer, Jolanda M A, Chen, Peng, Daimon, Makoto, Eriksson, Johan, Perola, Markus, Friedlander, Yechiel, Gao, Yu-Tang, Heppe, Denise H M, Holloway, John W, Houston, Denise K, Kanoni, Stavroula, Kim, Yu-Mi, Laaksonen, Maarit A, Jääskeläinen, Tiina, Lee, Nanette R, Lehtimäki, Terho, Lemaitre, Rozenn N, Lu, Wei, Luben, Robert N, Manichaikul, Ani, Männistö, Satu, Marques-Vidal, Pedro, Monda, Keri L, Ngwa, Julius S, Perusse, Louis, van Rooij, Frank J A, Xiang, Yong-Bing, Wen, Wanqing, Wojczynski, Mary K, Zhu, Jingwen, Borecki, Ingrid B, Bouchard, Claude, Cai, Qiuyin, Cooper, Cyrus, Dedoussis, George V, Deloukas, Panos, Ferrucci, Luigi, Forouhi, Nita G, Hansen, Torben, Christiansen, Lene, Hofman, Albert, Johansson, Ingegerd, Jørgensen, Torben, Karasawa, Shigeru, Khaw, Kay-Tee, Kim, Mi-Kyung, Kristiansson, Kati, Li, Huaixing, Lin, Xu, Liu, Yongmei, Lohman, Kurt K, Long, Jirong, Mikkilä, Vera, Mozaffarian, Dariush, North, Kari, Pedersen, Oluf, Raitakari, Olli, Rissanen, Harri, Tuomilehto, Jaakko, van der Schouw, Yvonne T, Uitterlinden, André G, Carola Zillikens, M, Franco, Oscar H, Shyong Tai, E, Ou Shu, Xiao, Siscovick, David S, Toft, Ulla, Monique Verschuren, W M, Vollenweider, Peter, Wareham, Nicholas J, Witteman, Jacqueline C M, Zheng, Wei, Ridker, Paul M, Kang, Jae H, Liang, Liming, Jensen, Majken K, Curhan, Gary C, Pasquale, Louis R, Hunter, David J, Mohlke, Karen L, Uusitupa, Matti, Adrienne Cupples, L, Rankinen, Tuomo, Orho-Melander, Marju, Wang, Tao, Chasman, Daniel I, Franks, Paul W, Sørensen, Thorkild I A, Hu, Frank B, Loos, Ruth J F, Nettleton, Jennifer A, and Qi, Lu

Abstract

FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.

Published
2014

237. Gene × Physical Activity Interactions in Obesity : Combined Analysis of 111,421 Individuals of European Ancestry

Author

Ahmad, Shafqat, Rukh, Gull, Varga, Tibor V., Ali, Ashfaq, Kurbasic, Azra, Shungin, Dmitry, Ericson, Ulrika, Koivula, Robert W., Chu, Audrey Y., Rose, Lynda M., Ganna, Andrea, Qi, Qibin, Stančáková, Alena, Sandholt, Camilla H., Elks, Cathy E., Curhan, Gary, Jensen, Majken K., Tamimi, Rulla M., Allin, Kristine H., Jørgensen, Torben, Brage, Soren, Langenberg, Claudia, Aadahl, Mette, Grarup, Niels, Linneberg, Allan, Paré, Guillaume, Magnusson, Patrik K. E., Pedersen, Nancy L., Boehnke, Michael, Hamsten, Anders, Mohlke, Karen L., Pasquale, Louis T., Pedersen, Oluf, Scott, Robert A., Ridker, Paul M., Ingelsson, Erik, Laakso, Markku, Hansen, Torben, Qi, Lu, Wareham, Nicholas J., Chasman, Daniel I., Hallmans, Göran, Hu, Frank B., Renström, Frida, Orho-Melander, Marju, Franks, Paul W., Ahmad, Shafqat, Rukh, Gull, Varga, Tibor V., Ali, Ashfaq, Kurbasic, Azra, Shungin, Dmitry, Ericson, Ulrika, Koivula, Robert W., Chu, Audrey Y., Rose, Lynda M., Ganna, Andrea, Qi, Qibin, Stančáková, Alena, Sandholt, Camilla H., Elks, Cathy E., Curhan, Gary, Jensen, Majken K., Tamimi, Rulla M., Allin, Kristine H., Jørgensen, Torben, Brage, Soren, Langenberg, Claudia, Aadahl, Mette, Grarup, Niels, Linneberg, Allan, Paré, Guillaume, Magnusson, Patrik K. E., Pedersen, Nancy L., Boehnke, Michael, Hamsten, Anders, Mohlke, Karen L., Pasquale, Louis T., Pedersen, Oluf, Scott, Robert A., Ridker, Paul M., Ingelsson, Erik, Laakso, Markku, Hansen, Torben, Qi, Lu, Wareham, Nicholas J., Chasman, Daniel I., Hallmans, Göran, Hu, Frank B., Renström, Frida, Orho-Melander, Marju, and Franks, Paul W.

Abstract

Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age2, sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS × physical activity interaction effect estimate (Pinteraction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, Pinteraction = 0.014 vs. n = 71,611, Pinteraction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (Pinteraction = 0.003) and the SEC16B rs10913469 (Pinteraction = 0.025) variants showed evidence of SNP × physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.

Published
2013
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238. Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders

Author

den Hoed, Marcel, Eijgelsheim, Mark, Esko, Tonu, Brundel, Bianca J. J. M., Peal, David S., Evans, David M., Nolte, Ilja M., Segre, Ayellet V., Holm, Hilma, Handsaker, Robert E., Westra, Harm-Jan, Johnson, Toby, Isaacs, Aaron, Yang, Jian, Lundby, Alicia, Zhao, Jing Hua, Kim, Young Jin, Go, Min Jin, Almgren, Peter, Bochud, Murielle, Boucher, Gabrielle, Cornelis, Marilyn C., Gudbjartsson, Daniel, Hadley, David, van der Harst, Pim, Hayward, Caroline, den Heijer, Martin, Igl, Wilmar, Jackson, Anne U., Kutalik, Zoltan, Luan, Jian'an, Kemp, John P., Kristiansson, Kati, Ladenvall, Claes, Lorentzon, Mattias, Montasser, May E., Njajou, Omer T., O'Reilly, Paul F., Padmanabhan, Sandosh, Pourcain, Beate St., Rankinen, Tuomo, Salo, Perttu, Tanaka, Toshiko, Timpson, Nicholas J., Vitart, Veronique, Waite, Lindsay, Wheeler, William, Zhang, Weihua, Draisma, Harmen H. M., Feitosa, Mary F., Kerr, Kathleen F., Lind, Penelope A., Mihailov, Evelin, Onland-Moret, N. Charlotte, Song, Ci, Weedon, Michael N., Xie, Weijia, Yengo, Loic, Absher, Devin, Albert, Christine M., Alonso, Alvaro, Arking, Dan E., de Bakker, Paul I. W., Balkau, Beverley, Barlassina, Cristina, Benaglio, Paola, Bis, Joshua C., Bouatia-Naji, Nabila, Brage, Soren, Chanock, Stephen J., Chines, Peter S., Chung, Mina, Darbar, Dawood, Dina, Christian, Doerr, Marcus, Elliott, Paul, Felix, Stephan B., Fischer, Krista, Fuchsberger, Christian, de Geus, Eco J. C., Goyette, Philippe, Gudnason, Vilmundur, Harris, Tamara B., Hartikainen, Anna-Liisa, Havulinna, Aki S., Heckbert, Susan R., Hicks, Andrew A., Hofman, Albert, Holewijn, Suzanne, Hoogstra-Berends, Femke, Hottenga, Jouke-Jan, Jensen, Majken K., Johansson, Asa, Junttila, Juhani, Kaeaeb, Stefan, Kanon, Bart, Ketkar, Shamika, Khaw, Kay-Tee, Knowles, Joshua W., Kooner, Angrad S., Kors, Jan A., Kumari, Meena, Milani, Lili, Laiho, Paeivi, Lakatta, Edward G., Langenberg, Claudia, Leusink, Maarten, Liu, Yongmei, Luben, Robert N., Lunetta, Kathryn L., Lynch, Stacey N., Markus, Marcello R. P., Marques-Vidal, Pedro, Leach, Irene Mateo, McArdle, Wendy L., McCarroll, Steven A., Medland, Sarah E., Miller, Kathryn A., Montgomery, Grant W., Morrison, Alanna C., Mueller-Nurasyid, Martina, Navarro, Pau, Nelis, Mari, O'Connell, Jeffrey R., O'Donnell, Christopher J., Ong, Ken K., Newman, Anne B., Peters, Annette, Polasek, Ozren, Pouta, Anneli, Pramstaller, Peter P., Psaty, Bruce M., Rao, Dabeeru C., Ring, Susan M., Rossin, Elizabeth J., Rudan, Diana, Sanna, Serena, Scott, Robert A., Sehmi, Jaban S., Sharp, Stephen, Shin, Jordan T., Singleton, Andrew B., Smith, Albert V., Soranzo, Nicole, Spector, Tim D., Stewart, Chip, Stringham, Heather M., Tarasov, Kirill V., Uitterlinden, Andre G., Vandenput, Liesbeth, Hwang, Shih-Jen, Whitfield, John B., Wijmenga, Cisca, Wild, Sarah H., Willemsen, Gonneke, Wilson, James F., Witteman, Jacqueline C. M., Wong, Andrew, Wong, Quenna, Jamshidi, Yalda, Zitting, Paavo, Boer, Jolanda M. A., Boomsma, Dorret I., Borecki, Ingrid B., van Duijn, Cornelia M., Ekelund, Ulf, Forouhi, Nita G., Froguel, Philippe, Hingorani, Aroon, Ingelsson, Erik, Kivimaki, Mika, Kronmal, Richard A., Kuh, Diana, Lind, Lars, Martin, Nicholas G., Oostra, Ben A., Pedersen, Nancy L., Quertermous, Thomas, Rotter, Jerome I., van der Schouw, Yvonne T., Verschuren, W. M. Monique, Walker, Mark, Albanes, Demetrius, Arnar, David O., Assimes, Themistocles L., Bandinelli, Stefania, Boehnke, Michael, de Boer, Rudolf A., Bouchard, Claude, Caulfield, W. L. Mark, Chambers, John C., Curhan, Gary, Cusi, Daniele, Eriksson, Johan, Ferrucci, Luigi, van Gilst, Wiek H., Glorioso, Nicola, de Graaf, Jacqueline, Groop, Leif, Gyllensten, Ulf, Hsueh, Wen-Chi, Hu, Frank B., Huikuri, Heikki V., Hunter, David J., Iribarren, Carlos, Isomaa, Bo, Jarvelin, Marjo-Riitta, Jula, Antti, Kahonen, Mika, Kiemeney, Lambertus A., van der Klauw, Melanie M., Kooner, Jaspal S., Kraft, Peter, Iacoviello, Licia, Lehtimaki, Terho, Lokki, Marja-Liisa L., Mitchell, Braxton D., Navis, Gerjan, Nieminen, Markku S., Ohlsson, Claes, Poulter, Neil R., Qi, Lu, Raitakari, Olli T., Rimm, Eric B., Rioux, John D., Rizzi, Federica, Rudan, Igor, Salomaa, Veikko, Sever, Peter S., Shields, Denis C., Shuldiner, Alan R., Sinisalo, Juha, Stanton, Alice V., Stolk, Ronald P., Strachan, David P., Tardif, Jean-Claude, Thorsteinsdottir, Unnur, Tuomilehto, Jaako, van Veldhuisen, Dirk J., Virtamo, Jarmo, Viikari, Jorma, Vollenweider, Peter, Waeber, Gerard, Widen, Elisabeth, Cho, Yoon Shin, Olsen, Jesper V., Visscher, Peter M., Willer, Cristen, Franke, Lude, Erdmann, Jeanette, Thompson, John R., Pfeufer, Arne, Sotoodehnia, Nona, Newton-Cheh, Christopher, Ellinor, Patrick T., Stricker, Bruno H. Ch, Metspalu, Andres, Perola, Markus, Beckmann, Jacques S., Smith, George Davey, Stefansson, Kari, Wareham, Nicholas J., Munroe, Patricia B., Sibon, Ody C. M., Milan, David J., Snieder, Harold, Samani, Nilesh J., Loos, Ruth J. F., den Hoed, Marcel, Eijgelsheim, Mark, Esko, Tonu, Brundel, Bianca J. J. M., Peal, David S., Evans, David M., Nolte, Ilja M., Segre, Ayellet V., Holm, Hilma, Handsaker, Robert E., Westra, Harm-Jan, Johnson, Toby, Isaacs, Aaron, Yang, Jian, Lundby, Alicia, Zhao, Jing Hua, Kim, Young Jin, Go, Min Jin, Almgren, Peter, Bochud, Murielle, Boucher, Gabrielle, Cornelis, Marilyn C., Gudbjartsson, Daniel, Hadley, David, van der Harst, Pim, Hayward, Caroline, den Heijer, Martin, Igl, Wilmar, Jackson, Anne U., Kutalik, Zoltan, Luan, Jian'an, Kemp, John P., Kristiansson, Kati, Ladenvall, Claes, Lorentzon, Mattias, Montasser, May E., Njajou, Omer T., O'Reilly, Paul F., Padmanabhan, Sandosh, Pourcain, Beate St., Rankinen, Tuomo, Salo, Perttu, Tanaka, Toshiko, Timpson, Nicholas J., Vitart, Veronique, Waite, Lindsay, Wheeler, William, Zhang, Weihua, Draisma, Harmen H. M., Feitosa, Mary F., Kerr, Kathleen F., Lind, Penelope A., Mihailov, Evelin, Onland-Moret, N. Charlotte, Song, Ci, Weedon, Michael N., Xie, Weijia, Yengo, Loic, Absher, Devin, Albert, Christine M., Alonso, Alvaro, Arking, Dan E., de Bakker, Paul I. W., Balkau, Beverley, Barlassina, Cristina, Benaglio, Paola, Bis, Joshua C., Bouatia-Naji, Nabila, Brage, Soren, Chanock, Stephen J., Chines, Peter S., Chung, Mina, Darbar, Dawood, Dina, Christian, Doerr, Marcus, Elliott, Paul, Felix, Stephan B., Fischer, Krista, Fuchsberger, Christian, de Geus, Eco J. C., Goyette, Philippe, Gudnason, Vilmundur, Harris, Tamara B., Hartikainen, Anna-Liisa, Havulinna, Aki S., Heckbert, Susan R., Hicks, Andrew A., Hofman, Albert, Holewijn, Suzanne, Hoogstra-Berends, Femke, Hottenga, Jouke-Jan, Jensen, Majken K., Johansson, Asa, Junttila, Juhani, Kaeaeb, Stefan, Kanon, Bart, Ketkar, Shamika, Khaw, Kay-Tee, Knowles, Joshua W., Kooner, Angrad S., Kors, Jan A., Kumari, Meena, Milani, Lili, Laiho, Paeivi, Lakatta, Edward G., Langenberg, Claudia, Leusink, Maarten, Liu, Yongmei, Luben, Robert N., Lunetta, Kathryn L., Lynch, Stacey N., Markus, Marcello R. P., Marques-Vidal, Pedro, Leach, Irene Mateo, McArdle, Wendy L., McCarroll, Steven A., Medland, Sarah E., Miller, Kathryn A., Montgomery, Grant W., Morrison, Alanna C., Mueller-Nurasyid, Martina, Navarro, Pau, Nelis, Mari, O'Connell, Jeffrey R., O'Donnell, Christopher J., Ong, Ken K., Newman, Anne B., Peters, Annette, Polasek, Ozren, Pouta, Anneli, Pramstaller, Peter P., Psaty, Bruce M., Rao, Dabeeru C., Ring, Susan M., Rossin, Elizabeth J., Rudan, Diana, Sanna, Serena, Scott, Robert A., Sehmi, Jaban S., Sharp, Stephen, Shin, Jordan T., Singleton, Andrew B., Smith, Albert V., Soranzo, Nicole, Spector, Tim D., Stewart, Chip, Stringham, Heather M., Tarasov, Kirill V., Uitterlinden, Andre G., Vandenput, Liesbeth, Hwang, Shih-Jen, Whitfield, John B., Wijmenga, Cisca, Wild, Sarah H., Willemsen, Gonneke, Wilson, James F., Witteman, Jacqueline C. M., Wong, Andrew, Wong, Quenna, Jamshidi, Yalda, Zitting, Paavo, Boer, Jolanda M. A., Boomsma, Dorret I., Borecki, Ingrid B., van Duijn, Cornelia M., Ekelund, Ulf, Forouhi, Nita G., Froguel, Philippe, Hingorani, Aroon, Ingelsson, Erik, Kivimaki, Mika, Kronmal, Richard A., Kuh, Diana, Lind, Lars, Martin, Nicholas G., Oostra, Ben A., Pedersen, Nancy L., Quertermous, Thomas, Rotter, Jerome I., van der Schouw, Yvonne T., Verschuren, W. M. Monique, Walker, Mark, Albanes, Demetrius, Arnar, David O., Assimes, Themistocles L., Bandinelli, Stefania, Boehnke, Michael, de Boer, Rudolf A., Bouchard, Claude, Caulfield, W. L. Mark, Chambers, John C., Curhan, Gary, Cusi, Daniele, Eriksson, Johan, Ferrucci, Luigi, van Gilst, Wiek H., Glorioso, Nicola, de Graaf, Jacqueline, Groop, Leif, Gyllensten, Ulf, Hsueh, Wen-Chi, Hu, Frank B., Huikuri, Heikki V., Hunter, David J., Iribarren, Carlos, Isomaa, Bo, Jarvelin, Marjo-Riitta, Jula, Antti, Kahonen, Mika, Kiemeney, Lambertus A., van der Klauw, Melanie M., Kooner, Jaspal S., Kraft, Peter, Iacoviello, Licia, Lehtimaki, Terho, Lokki, Marja-Liisa L., Mitchell, Braxton D., Navis, Gerjan, Nieminen, Markku S., Ohlsson, Claes, Poulter, Neil R., Qi, Lu, Raitakari, Olli T., Rimm, Eric B., Rioux, John D., Rizzi, Federica, Rudan, Igor, Salomaa, Veikko, Sever, Peter S., Shields, Denis C., Shuldiner, Alan R., Sinisalo, Juha, Stanton, Alice V., Stolk, Ronald P., Strachan, David P., Tardif, Jean-Claude, Thorsteinsdottir, Unnur, Tuomilehto, Jaako, van Veldhuisen, Dirk J., Virtamo, Jarmo, Viikari, Jorma, Vollenweider, Peter, Waeber, Gerard, Widen, Elisabeth, Cho, Yoon Shin, Olsen, Jesper V., Visscher, Peter M., Willer, Cristen, Franke, Lude, Erdmann, Jeanette, Thompson, John R., Pfeufer, Arne, Sotoodehnia, Nona, Newton-Cheh, Christopher, Ellinor, Patrick T., Stricker, Bruno H. Ch, Metspalu, Andres, Perola, Markus, Beckmann, Jacques S., Smith, George Davey, Stefansson, Kari, Wareham, Nicholas J., Munroe, Patricia B., Sibon, Ody C. M., Milan, David J., Snieder, Harold, Samani, Nilesh J., and Loos, Ruth J. F.

Abstract

Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.

Published
2013
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239. A genome-wide association study of depressive symptoms.

Author

Hek, Karin, Hek, Karin, Demirkan, Ayse, Lahti, Jari, Terracciano, Antonio, Teumer, Alexander, Cornelis, Marilyn C, Amin, Najaf, Bakshis, Erin, Baumert, Jens, Ding, Jingzhong, Liu, Yongmei, Marciante, Kristin, Meirelles, Osorio, Nalls, Michael A, Sun, Yan V, Vogelzangs, Nicole, Yu, Lei, Bandinelli, Stefania, Benjamin, Emelia J, Bennett, David A, Boomsma, Dorret, Cannas, Alessandra, Coker, Laura H, de Geus, Eco, De Jager, Philip L, Diez-Roux, Ana V, Purcell, Shaun, Hu, Frank B, Rimma, Eric B, Hunter, David J, Jensen, Majken K, Curhan, Gary, Rice, Kenneth, Penman, Alan D, Rotter, Jerome I, Sotoodehnia, Nona, Emeny, Rebecca, Eriksson, Johan G, Evans, Denis A, Ferrucci, Luigi, Fornage, Myriam, Gudnason, Vilmundur, Hofman, Albert, Illig, Thomas, Kardia, Sharon, Kelly-Hayes, Margaret, Koenen, Karestan, Kraft, Peter, Kuningas, Maris, Massaro, Joseph M, Melzer, David, Mulas, Antonella, Mulder, Cornelis L, Murray, Anna, Oostra, Ben A, Palotie, Aarno, Penninx, Brenda, Petersmann, Astrid, Pilling, Luke C, Psaty, Bruce, Rawal, Rajesh, Reiman, Eric M, Schulz, Andrea, Shulman, Joshua M, Singleton, Andrew B, Smith, Albert V, Sutin, Angelina R, Uitterlinden, André G, Völzke, Henry, Widen, Elisabeth, Yaffe, Kristine, Zonderman, Alan B, Cucca, Francesco, Harris, Tamara, Ladwig, Karl-Heinz, Llewellyn, David J, Räikkönen, Katri, Tanaka, Toshiko, van Duijn, Cornelia M, Grabe, Hans J, Launer, Lenore J, Lunetta, Kathryn L, Mosley, Thomas H, Newman, Anne B, Tiemeier, Henning, Murabito, Joanne, Hek, Karin, Hek, Karin, Demirkan, Ayse, Lahti, Jari, Terracciano, Antonio, Teumer, Alexander, Cornelis, Marilyn C, Amin, Najaf, Bakshis, Erin, Baumert, Jens, Ding, Jingzhong, Liu, Yongmei, Marciante, Kristin, Meirelles, Osorio, Nalls, Michael A, Sun, Yan V, Vogelzangs, Nicole, Yu, Lei, Bandinelli, Stefania, Benjamin, Emelia J, Bennett, David A, Boomsma, Dorret, Cannas, Alessandra, Coker, Laura H, de Geus, Eco, De Jager, Philip L, Diez-Roux, Ana V, Purcell, Shaun, Hu, Frank B, Rimma, Eric B, Hunter, David J, Jensen, Majken K, Curhan, Gary, Rice, Kenneth, Penman, Alan D, Rotter, Jerome I, Sotoodehnia, Nona, Emeny, Rebecca, Eriksson, Johan G, Evans, Denis A, Ferrucci, Luigi, Fornage, Myriam, Gudnason, Vilmundur, Hofman, Albert, Illig, Thomas, Kardia, Sharon, Kelly-Hayes, Margaret, Koenen, Karestan, Kraft, Peter, Kuningas, Maris, Massaro, Joseph M, Melzer, David, Mulas, Antonella, Mulder, Cornelis L, Murray, Anna, Oostra, Ben A, Palotie, Aarno, Penninx, Brenda, Petersmann, Astrid, Pilling, Luke C, Psaty, Bruce, Rawal, Rajesh, Reiman, Eric M, Schulz, Andrea, Shulman, Joshua M, Singleton, Andrew B, Smith, Albert V, Sutin, Angelina R, Uitterlinden, André G, Völzke, Henry, Widen, Elisabeth, Yaffe, Kristine, Zonderman, Alan B, Cucca, Francesco, Harris, Tamara, Ladwig, Karl-Heinz, Llewellyn, David J, Räikkönen, Katri, Tanaka, Toshiko, van Duijn, Cornelia M, Grabe, Hans J, Launer, Lenore J, Lunetta, Kathryn L, Mosley, Thomas H, Newman, Anne B, Tiemeier, Henning, and Murabito, Joanne

Abstract

BackgroundDepression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms.MethodsIn this genome-wide association study, we combined the results of 17 population-based studies assessing depressive symptoms with the Center for Epidemiological Studies Depression Scale. Replication of the independent top hits (p<1×10(-5)) was performed in five studies assessing depressive symptoms with other instruments. In addition, we performed a combined meta-analysis of all 22 discovery and replication studies.ResultsThe discovery sample comprised 34,549 individuals (mean age of 66.5) and no loci reached genome-wide significance (lowest p = 1.05×10(-7)). Seven independent single nucleotide polymorphisms were considered for replication. In the replication set (n = 16,709), we found suggestive association of one single nucleotide polymorphism with depressive symptoms (rs161645, 5q21, p = 9.19×10(-3)). This 5q21 region reached genome-wide significance (p = 4.78×10(-8)) in the overall meta-analysis combining discovery and replication studies (n = 51,258).ConclusionsThe results suggest that only a large sample comprising more than 50,000 subjects may be sufficiently powered to detect genes for depressive symptoms.

Published
2013

240. Gene x Physical Activity Interactions in Obesity: Combined Analysis of 111,421 Individuals of European Ancestry

Author

Ahmad, Shafqat, Rukh, Gull, Varga, Tibor V., Ali, Ashfaq, Kurbasic, Azra, Shungin, Dmitry, Ericson, Ulrika, Koivula, Robert W., Chu, Audrey Y., Rose, Lynda M., Ganna, Andrea, Qi, Qibin, Stancakova, Alena, Sandholt, Camilla H., Elks, Cathy E., Curhan, Gary, Jensen, Majken K., Tamimi, Rulla M., Allin, Kristine H., Jorgensen, Torben, Brage, Soren, Langenberg, Claudia, Aadahl, Mette, Grarup, Niels, Linneberg, Allan, Pare, Guillaume, Magnusson, Patrik K. E., Pedersen, Nancy L., Boehnke, Michael, Hamsten, Anders, Mohlke, Karen L., Pasquale, Louis T., Pedersen, Oluf, Scott, Robert A., Ridker, Paul M., Ingelsson, Erik, Laakso, Markku, Hansen, Torben, Qi, Lu, Wareham, Nicholas J., Chasman, Daniel I., Hallmans, Goran, Hu, Frank B., Renstrom, Frida, Orho-Melander, Marju, Franks, Paul W., Ahmad, Shafqat, Rukh, Gull, Varga, Tibor V., Ali, Ashfaq, Kurbasic, Azra, Shungin, Dmitry, Ericson, Ulrika, Koivula, Robert W., Chu, Audrey Y., Rose, Lynda M., Ganna, Andrea, Qi, Qibin, Stancakova, Alena, Sandholt, Camilla H., Elks, Cathy E., Curhan, Gary, Jensen, Majken K., Tamimi, Rulla M., Allin, Kristine H., Jorgensen, Torben, Brage, Soren, Langenberg, Claudia, Aadahl, Mette, Grarup, Niels, Linneberg, Allan, Pare, Guillaume, Magnusson, Patrik K. E., Pedersen, Nancy L., Boehnke, Michael, Hamsten, Anders, Mohlke, Karen L., Pasquale, Louis T., Pedersen, Oluf, Scott, Robert A., Ridker, Paul M., Ingelsson, Erik, Laakso, Markku, Hansen, Torben, Qi, Lu, Wareham, Nicholas J., Chasman, Daniel I., Hallmans, Goran, Hu, Frank B., Renstrom, Frida, Orho-Melander, Marju, and Franks, Paul W.

Published
2013

241. Gene × physical activity interactions in obesity:combined analysis of 111,421 individuals of European ancestry

Author

Ahmad, Shafqat, Rukh, Gull, Varga, Tibor V, Ali, Ashfaq, Kurbasic, Azra, Shungin, Dmitry, Ericson, Ulrika, Koivula, Robert W, Chu, Audrey Y, Rose, Lynda M, Ganna, Andrea, Qi, Qibin, Stančáková, Alena, Sandholt, Camilla H, Elks, Cathy E, Curhan, Gary, Jensen, Majken K, Tamimi, Rulla M, Allin, Kristine H, Jørgensen, Torben, Brage, Soren, Langenberg, Claudia, Aadahl, Mette, Grarup, Niels, Linneberg, Allan, Paré, Guillaume, Magnusson, Patrik K E, Pedersen, Nancy L, Boehnke, Michael, Hamsten, Anders, Mohlke, Karen L, Pasquale, Louis T, Pedersen, Oluf, Scott, Robert A, Ridker, Paul M, Ingelsson, Erik, Laakso, Markku, Hansen, Torben, Qi, Lu, Wareham, Nicholas J, Chasman, Daniel I, Hallmans, Göran, Hu, Frank B, Renström, Frida, Orho-Melander, Marju, Franks, Paul W, Ahmad, Shafqat, Rukh, Gull, Varga, Tibor V, Ali, Ashfaq, Kurbasic, Azra, Shungin, Dmitry, Ericson, Ulrika, Koivula, Robert W, Chu, Audrey Y, Rose, Lynda M, Ganna, Andrea, Qi, Qibin, Stančáková, Alena, Sandholt, Camilla H, Elks, Cathy E, Curhan, Gary, Jensen, Majken K, Tamimi, Rulla M, Allin, Kristine H, Jørgensen, Torben, Brage, Soren, Langenberg, Claudia, Aadahl, Mette, Grarup, Niels, Linneberg, Allan, Paré, Guillaume, Magnusson, Patrik K E, Pedersen, Nancy L, Boehnke, Michael, Hamsten, Anders, Mohlke, Karen L, Pasquale, Louis T, Pedersen, Oluf, Scott, Robert A, Ridker, Paul M, Ingelsson, Erik, Laakso, Markku, Hansen, Torben, Qi, Lu, Wareham, Nicholas J, Chasman, Daniel I, Hallmans, Göran, Hu, Frank B, Renström, Frida, Orho-Melander, Marju, and Franks, Paul W

Abstract

Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS × physical activity interaction effect estimate (Pinteraction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, Pinteraction = 0.014 vs. n = 71,611, Pinteraction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (Pinteraction = 0.003) and the SEC16B rs10913469 (Pinteraction = 0.025) variants showed evidence of SNP × physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.

Published
2013

243. Plasma HDL cholesterol and risk of myocardial infarction : a mendelian randomisation study

Author

Voight, Benjamin F, Peloso, Gina M, Orho-Melander, Marju, Frikke-Schmidt, Ruth, Barbalic, Maja, Jensen, Majken K, Hindy, George, Hólm, Hilma, Ding, Eric L, Johnson, Toby, Schunkert, Heribert, Samani, Nilesh J, Clarke, Robert, Hopewell, Jemma C, Thompson, John F, Li, Mingyao, Thorleifsson, Gudmar, Newton-Cheh, Christopher, Musunuru, Kiran, Pirruccello, James P, Saleheen, Danish, Chen, Li, Stewart, Alexandre F R, Schillert, Arne, Thorsteinsdottir, Unnur, Thorgeirsson, Gudmundur, Anand, Sonia, Engert, James C, Morgan, Thomas, Spertus, John, Stoll, Monika, Berger, Klaus, Martinelli, Nicola, Girelli, Domenico, McKeown, Pascal P, Patterson, Christopher C, Epstein, Stephen E, Devaney, Joseph, Burnett, Mary-Susan, Mooser, Vincent, Ripatti, Samuli, Surakka, Ida, Nieminen, Markku S, Sinisalo, Juha, Lokki, Marja-Liisa, Perola, Markus, Havulinna, Aki, de Faire, Ulf, Gigante, Bruna, Ingelsson, Erik, Zeller, Tanja, Wild, Philipp, de Bakker, Paul I W, Klungel, Olaf H, Maitland-van der Zee, Anke-Hilse, Peters, Bas J M, de Boer, Anthonius, Grobbee, Diederick E, Kamphuisen, Pieter W, Deneer, Vera H M, Elbers, Clara C, Onland-Moret, N Charlotte, Hofker, Marten H, Wijmenga, Cisca, Verschuren, W M Monique, Boer, Jolanda M A, van der Schouw, Yvonne T, Rasheed, Asif, Frossard, Philippe, Demissie, Serkalem, Willer, Cristen, Do, Ron, Ordovas, Jose M, Abecasis, Gonçalo R, Boehnke, Michael, Mohlke, Karen L, Daly, Mark J, Guiducci, Candace, Burtt, Noël P, Surti, Aarti, Gonzalez, Elena, Purcell, Shaun, Gabriel, Stacey, Marrugat, Jaume, Peden, John, Erdmann, Jeanette, Diemert, Patrick, Willenborg, Christina, König, Inke R, Fischer, Marcus, Hengstenberg, Christian, Ziegler, Andreas, Buysschaert, Ian, Lambrechts, Diether, Van de Werf, Frans, Fox, Keith A, El Mokhtari, Nour Eddine, Rubin, Diana, Schrezenmeir, Jürgen, Schreiber, Stefan, Schäfer, Arne, Danesh, John, Blankenberg, Stefan, Roberts, Robert, McPherson, Ruth, Watkins, Hugh, Hall, Alistair S, Overvad, Kim, Rimm, Eric, Boerwinkle, Eric, Tybjaerg-Hansen, Anne, Cupples, L Adrienne, Reilly, Muredach P, Melander, Olle, Mannucci, Pier M, Ardissino, Diego, Siscovick, David, Elosua, Roberto, Stefansson, Kari, O'Donnell, Christopher J, Salomaa, Veikko, Rader, Daniel J, Peltonen, Leena, Schwartz, Stephen M, Altshuler, David, Kathiresan, Sekar, Voight, Benjamin F, Peloso, Gina M, Orho-Melander, Marju, Frikke-Schmidt, Ruth, Barbalic, Maja, Jensen, Majken K, Hindy, George, Hólm, Hilma, Ding, Eric L, Johnson, Toby, Schunkert, Heribert, Samani, Nilesh J, Clarke, Robert, Hopewell, Jemma C, Thompson, John F, Li, Mingyao, Thorleifsson, Gudmar, Newton-Cheh, Christopher, Musunuru, Kiran, Pirruccello, James P, Saleheen, Danish, Chen, Li, Stewart, Alexandre F R, Schillert, Arne, Thorsteinsdottir, Unnur, Thorgeirsson, Gudmundur, Anand, Sonia, Engert, James C, Morgan, Thomas, Spertus, John, Stoll, Monika, Berger, Klaus, Martinelli, Nicola, Girelli, Domenico, McKeown, Pascal P, Patterson, Christopher C, Epstein, Stephen E, Devaney, Joseph, Burnett, Mary-Susan, Mooser, Vincent, Ripatti, Samuli, Surakka, Ida, Nieminen, Markku S, Sinisalo, Juha, Lokki, Marja-Liisa, Perola, Markus, Havulinna, Aki, de Faire, Ulf, Gigante, Bruna, Ingelsson, Erik, Zeller, Tanja, Wild, Philipp, de Bakker, Paul I W, Klungel, Olaf H, Maitland-van der Zee, Anke-Hilse, Peters, Bas J M, de Boer, Anthonius, Grobbee, Diederick E, Kamphuisen, Pieter W, Deneer, Vera H M, Elbers, Clara C, Onland-Moret, N Charlotte, Hofker, Marten H, Wijmenga, Cisca, Verschuren, W M Monique, Boer, Jolanda M A, van der Schouw, Yvonne T, Rasheed, Asif, Frossard, Philippe, Demissie, Serkalem, Willer, Cristen, Do, Ron, Ordovas, Jose M, Abecasis, Gonçalo R, Boehnke, Michael, Mohlke, Karen L, Daly, Mark J, Guiducci, Candace, Burtt, Noël P, Surti, Aarti, Gonzalez, Elena, Purcell, Shaun, Gabriel, Stacey, Marrugat, Jaume, Peden, John, Erdmann, Jeanette, Diemert, Patrick, Willenborg, Christina, König, Inke R, Fischer, Marcus, Hengstenberg, Christian, Ziegler, Andreas, Buysschaert, Ian, Lambrechts, Diether, Van de Werf, Frans, Fox, Keith A, El Mokhtari, Nour Eddine, Rubin, Diana, Schrezenmeir, Jürgen, Schreiber, Stefan, Schäfer, Arne, Danesh, John, Blankenberg, Stefan, Roberts, Robert, McPherson, Ruth, Watkins, Hugh, Hall, Alistair S, Overvad, Kim, Rimm, Eric, Boerwinkle, Eric, Tybjaerg-Hansen, Anne, Cupples, L Adrienne, Reilly, Muredach P, Melander, Olle, Mannucci, Pier M, Ardissino, Diego, Siscovick, David, Elosua, Roberto, Stefansson, Kari, O'Donnell, Christopher J, Salomaa, Veikko, Rader, Daniel J, Peltonen, Leena, Schwartz, Stephen M, Altshuler, David, and Kathiresan, Sekar

Abstract

BACKGROUND: High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal. METHODS: We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20,913 myocardial infarction cases, 95,407 controls). Second, we used as an instrument a genetic score consisting of 14 common SNPs that exclusively associate with HDL cholesterol and tested this score in up to 12,482 cases of myocardial infarction and 41,331 controls. As a positive control, we also tested a genetic score of 13 common SNPs exclusively associated with LDL cholesterol. FINDINGS: Carriers of the LIPG 396Ser allele (2·6% frequency) had higher HDL cholesterol (0·14 mmol/L higher, p=8×10(-13)) but similar levels of other lipid and non-lipid risk factors for myocardial infarction compared with non-carriers. This difference in HDL cholesterol is expected to decrease risk of myocardial infarction by 13% (odds ratio [OR] 0·87, 95% CI 0·84-0·91). However, we noted that the 396Ser allele was not associated with risk of myocardial infarction (OR 0·99, 95% CI 0·88-1·11, p=0·85). From observational epidemiology, an increase of 1 SD in HDL cholesterol was associated with reduced risk of myocardial infarction (OR 0·62, 95% CI 0·58-0·66). However, a 1 SD increase in HDL cholesterol due to genetic score was not associated with risk of myocardial infarction (OR 0·93, 95% CI 0·68-1·26, p=0·63). For LDL cholesterol, the estimate from observational epidemiology (a 1 SD increase in LDL cholesterol associated with OR 1·54, 95% CI 1·45-1·63) wa

Published
2012
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245. Protein interaction-based genome-wide analysis of incident coronary heart disease

Author

Jensen, Majken K, Pers, Tune H, Dworzynski, Piotr, Girman, Cynthia J, Brunak, Søren, Rimm, Eric B, Jensen, Majken K, Pers, Tune H, Dworzynski, Piotr, Girman, Cynthia J, Brunak, Søren, and Rimm, Eric B

Abstract

Network-based approaches may leverage genome-wide association (GWA) analysis by testing for the aggregate association across several pathway members. We aimed to examine if networks of genes that represent experimentally determined protein-protein interactions (PPIs) are enriched in genes associated with risk of coronary heart disease (CHD).

Published
2011

247. Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD

Author

University of Helsinki, Hjelt Institute, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Department of Public Health, Saccone, Nancy L., Culverhouse, Robert C., Schwantes-An, Tae-Hwi, Cannon, Dale S., Chen, Xiangning, Cichon, Sven, Giegling, Ina, Han, Shizhong, Han, Younghun, Keskitalo-Vuokko, Kaisu, Kong, Xiangyang, Landi, Maria Teresa, Ma, Jennie Z., Short, Susan E., Stephens, Sarah H., Stevens, Victoria L., Sun, Lingwei, Wang, Yufei, Wenzlaff, Angela S., Aggen, Steven H., Breslau, Naomi, Broderick, Peter, Chatterjee, Nilanjan, Chen, Jingchun, Heath, Andrew C., Heliovaara, Markku, Hoft, Nicole R., Hunter, David J., Jensen, Majken K., Martin, Nicholas G., Montgomery, Grant W., Niu, Tianhua, Payne, Thomas J., Palotie, Leena, Pergadia, Michele L., Rice, John P., Sherva, Richard, Spitz, Margaret R., Sun, Juzhong, Wang, Jen C., Weiss, Robert B., Wheeler, William, Witt, Stephanie H., Yang, Bao-Zhu, Caporaso, Neil E., Ehringer, Marissa A., Eisen, Tim, Gapstur, Susan M., Gelernter, Joel, Houlston, Richard, Kaprio, Jaakko, Kendler, Kenneth S., Kraft, Peter, Leppert, Mark F., Li, Ming D., Madden, Pamela A. F., Noethen, Markus M., Pillai, Sreekumar, Rietschel, Marcella, Rujescu, Dan, Schwartz, Ann, Amos, Christopher I., Bierut, Laura J., University of Helsinki, Hjelt Institute, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Department of Public Health, Saccone, Nancy L., Culverhouse, Robert C., Schwantes-An, Tae-Hwi, Cannon, Dale S., Chen, Xiangning, Cichon, Sven, Giegling, Ina, Han, Shizhong, Han, Younghun, Keskitalo-Vuokko, Kaisu, Kong, Xiangyang, Landi, Maria Teresa, Ma, Jennie Z., Short, Susan E., Stephens, Sarah H., Stevens, Victoria L., Sun, Lingwei, Wang, Yufei, Wenzlaff, Angela S., Aggen, Steven H., Breslau, Naomi, Broderick, Peter, Chatterjee, Nilanjan, Chen, Jingchun, Heath, Andrew C., Heliovaara, Markku, Hoft, Nicole R., Hunter, David J., Jensen, Majken K., Martin, Nicholas G., Montgomery, Grant W., Niu, Tianhua, Payne, Thomas J., Palotie, Leena, Pergadia, Michele L., Rice, John P., Sherva, Richard, Spitz, Margaret R., Sun, Juzhong, Wang, Jen C., Weiss, Robert B., Wheeler, William, Witt, Stephanie H., Yang, Bao-Zhu, Caporaso, Neil E., Ehringer, Marissa A., Eisen, Tim, Gapstur, Susan M., Gelernter, Joel, Houlston, Richard, Kaprio, Jaakko, Kendler, Kenneth S., Kraft, Peter, Leppert, Mark F., Li, Ming D., Madden, Pamela A. F., Noethen, Markus M., Pillai, Sreekumar, Rietschel, Marcella, Rujescu, Dan, Schwartz, Ann, Amos, Christopher I., and Bierut, Laura J.

Published
2010

248. A prospective analysis of the association between dietary fiber intake and prostate cancer risk in EPIC.

Author

Suzuki, Reiko, Allen, Naomi E, Key, Timothy J, Appleby, Paul N, Tjønneland, Anne, Johnsen, Nina Føns, Jensen, Majken K, Overvad, Kim, Boeing, Heiner, Pischon, Tobias, Kaaks, Rudolf, Rohrmann, Sabine, Trichopoulou, Antonia, Misirli, Gesthimani, Trichopoulos, Dimitrios, Bueno-de-Mesquita, H Bas, van Duijnhoven, Fränzel, Sacerdote, Carlotta, Pala, Valeria, Palli, Domenico, Tumino, Rosario, Ardanaz, Eva, Quirós, José Ramón, Larrañaga, Nerea, Sánchez, Maria-José, Tormo, María-José, Jakszyn, Paula, Johansson, Ingegerd, Stattin, Pär, Berglund, Göran, Manjer, Jonas, Bingham, Sheila, Khaw, Kay-Tee, Egevad, Lars, Ferrari, Pietro, Jenab, Mazda, Riboli, Elio, Suzuki, Reiko, Allen, Naomi E, Key, Timothy J, Appleby, Paul N, Tjønneland, Anne, Johnsen, Nina Føns, Jensen, Majken K, Overvad, Kim, Boeing, Heiner, Pischon, Tobias, Kaaks, Rudolf, Rohrmann, Sabine, Trichopoulou, Antonia, Misirli, Gesthimani, Trichopoulos, Dimitrios, Bueno-de-Mesquita, H Bas, van Duijnhoven, Fränzel, Sacerdote, Carlotta, Pala, Valeria, Palli, Domenico, Tumino, Rosario, Ardanaz, Eva, Quirós, José Ramón, Larrañaga, Nerea, Sánchez, Maria-José, Tormo, María-José, Jakszyn, Paula, Johansson, Ingegerd, Stattin, Pär, Berglund, Göran, Manjer, Jonas, Bingham, Sheila, Khaw, Kay-Tee, Egevad, Lars, Ferrari, Pietro, Jenab, Mazda, and Riboli, Elio

Abstract

Few studies have examined the association between dietary fiber intake and prostate cancer risk. We evaluated the association between dietary fiber intake and the risk of prostate cancer among 142,590 men in the European Prospective Investigation into Cancer and Nutrition (EPIC). Consumption of dietary fiber (total, cereal, fruit and vegetable fiber) was estimated by validated dietary questionnaires and calibrated using 24-hr dietary recalls. Incidence rate ratios were estimated using Cox regression and adjusted for potential confounding factors. During an average of 8.7 years follow-up, prostate cancer was diagnosed in 2,747 men. Overall, there was no association between dietary fiber intake (total, cereal, fruit or vegetable fiber) and prostate cancer risk, although calibrated intakes of total fiber and fruit fiber were associated with nonstatistically significant reductions in risk. There was no association between fiber derived from cereals or vegetables and risk and no evidence for heterogeneity in any of the risk estimates by stage or grade of disease. Our results suggest that dietary fiber intake is not associated with prostate cancer risk.

Published
2009
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249. S447X variant of the lipoprotein lipase gene, lipids, and risk of coronary heart disease in 3 prospective cohort studies

Author

Jensen, Majken K, Rimm, Eric B, Rader, Daniel, Schmidt, Erik B, Sørensen, Thorkild I A, Vogel, Ulla, Overvad, Kim, Mukamal, Kenneth J, Jensen, Majken K, Rimm, Eric B, Rader, Daniel, Schmidt, Erik B, Sørensen, Thorkild I A, Vogel, Ulla, Overvad, Kim, and Mukamal, Kenneth J

Abstract

Udgivelsesdato: 2009-Feb, BACKGROUND: Lipoprotein lipase (LPL) has a prominent role in the metabolism of triglycerides (TGs) and high-density lipoprotein cholesterol (HDL-C) and is a potential interesting target for the development of antiatherogenic treatment. To provide deeper insight into the role of natural variation in this gene, we investigated the association between the LPL S447X variant with lipids and risk of coronary heart disease (CHD) in 3 independent, prospective studies. METHODS: The S447X variant was genotyped in case-control studies of incident CHD nested within the Nurses' Health Study (NHS), the Health Professionals Follow-up Study (HPFS), and the Danish Diet, Cancer and Health (DCH) study, totaling 245, 258, and 962 cases, respectively. RESULTS: S447X carriers tended to have lower TG and higher HDL-C concentrations than noncarriers. The S447X variant was associated with a lower risk of CHD in the NHS; the association was weaker in the HPFS and not statistically significant in the DCH women and men. The pooled relative risk per minor allele was 0.74 (0.56-1.00). There was a suggestion that the associations of the S447X variant with plasma lipids and CHD risk were more pronounced in obese individuals in the NHS study, but this finding was not consistent across the studies. CONCLUSIONS: The LPL S447X variant tended to be associated with lower TG and higher HDL-C levels, and lower risk of CHD in all 3 cohorts. Lipoprotein lipase is an attractive target for clinical intervention, but studies are needed to clarify whether greater benefit from this variant may be conferred in some subgroups.

Published
2009

250. The T111I variant in the endothelial lipase gene and risk of coronary heart disease in three independent populations

Author

Jensen, Majken K, Rimm, Eric B, Mukamal, Kenneth J, Edmondson, Andrew C, Rader, Daniel J, Vogel, Ulla, Tjønneland, Anne, Sørensen, Thorkild I A, Schmidt, Erik B, Overvad, Kim, Jensen, Majken K, Rimm, Eric B, Mukamal, Kenneth J, Edmondson, Andrew C, Rader, Daniel J, Vogel, Ulla, Tjønneland, Anne, Sørensen, Thorkild I A, Schmidt, Erik B, and Overvad, Kim

Abstract

Udgivelsesdato: 2009-Jul, AIMS: Endothelial lipase (LIPG) is implicated in the metabolism of high-density lipoprotein cholesterol (HDL-C). Small studies in selected populations have reported higher HDL-C levels among carriers of the common T111I variant in LIPG, but whether this variant is associated with plasma lipids and risk of coronary heart disease (CHD) in the general population is unclear. The objective of this study was to address the associations of the T111I variant with plasma lipids and risk of CHD in three independent prospective studies of generally healthy men and women. METHODS AND RESULTS: The T111I variant was genotyped in case-control studies of CHD nested within the Diet, Cancer, and Health study with 998 cases, Nurses' Health Study with 241 cases, and Health Professionals Follow-up Study with 262 cases. The minor allele frequency in the combined pool of controls was 0.29. The T111I variant was not associated with HDL-C or any other lipid and lipoprotein measures. Compared with wildtype homozygotes, the pooled estimate for risk of CHD was 0.95 (0.85-1.06) per T111I allele. CONCLUSION: Our analysis among healthy Caucasian men and women from three independent studies does not support an association between the T111I variant and HDL-C, other plasma lipids, or risk of CHD.

Published
2009

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