Search

Your search keyword '"North, Kari E"' showing total 2,450 results
Start Over Author "North, Kari E"
2,450 results on '"North, Kari E"'

101. Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin

Author

Liu, Ching-Ti, Raghavan, Sridharan, Maruthur, Nisa, Kabagambe, Edmond Kato, Hong, Jaeyoung, Ng, Maggie CY, Hivert, Marie-France, Lu, Yingchang, An, Ping, Bentley, Amy R, Drolet, Anne M, Gaulton, Kyle J, Guo, Xiuqing, Armstrong, Loren L, Irvin, Marguerite R, Li, Man, Lipovich, Leonard, Rybin, Denis V, Taylor, Kent D, Agyemang, Charles, Palmer, Nicholette D, Cade, Brian E, Chen, Wei-Min, Dauriz, Marco, Delaney, Joseph AC, Edwards, Todd L, Evans, Daniel S, Evans, Michele K, Lange, Leslie A, Leong, Aaron, Liu, Jingmin, Liu, Yongmei, Nayak, Uma, Patel, Sanjay R, Porneala, Bianca C, Rasmussen-Torvik, Laura J, Snijder, Marieke B, Stallings, Sarah C, Tanaka, Toshiko, Yanek, Lisa R, Zhao, Wei, Becker, Diane M, Bielak, Lawrence F, Biggs, Mary L, Bottinger, Erwin P, Bowden, Donald W, Chen, Guanjie, Correa, Adolfo, Couper, David J, Crawford, Dana C, Cushman, Mary, Eicher, John D, Fornage, Myriam, Franceschini, Nora, Fu, Yi-Ping, Goodarzi, Mark O, Gottesman, Omri, Hara, Kazuo, Harris, Tamara B, Jensen, Richard A, Johnson, Andrew D, Jhun, Min A, Karter, Andrew J, Keller, Margaux F, Kho, Abel N, Kizer, Jorge R, Krauss, Ronald M, Langefeld, Carl D, Li, Xiaohui, Liang, Jingling, Liu, Simin, Lowe, William L, Mosley, Thomas H, North, Kari E, Pacheco, Jennifer A, Peyser, Patricia A, Patrick, Alan L, Rice, Kenneth M, Selvin, Elizabeth, Sims, Mario, Smith, Jennifer A, Tajuddin, Salman M, Vaidya, Dhananjay, Wren, Mary P, Yao, Jie, Zhu, Xiaofeng, Ziegler, Julie T, Zmuda, Joseph M, Zonderman, Alan B, Zwinderman, Aeilko H, Consortium, AAAG, Consortium, CARe, Consortium, COGENT-BP, Consortium, eMERGE, Consortium, MEDIA, Adeyemo, Adebowale, Boerwinkle, Eric, Ferrucci, Luigi, Hayes, M Geoffrey, and Kardia, Sharon LR

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Health Disparities, Human Genome, Diabetes, Minority Health, Metabolic and endocrine, Asian People, Black People, Blood Glucose, Diabetes Mellitus, Type 2, Enhancer Elements, Genetic, Ethnicity, Fasting, Female, Gene Frequency, Genome-Wide Association Study, Humans, Insulin, Insulin Resistance, Introns, Islets of Langerhans, Male, Molecular Sequence Annotation, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Racial Groups, Transcription Factors, White People, AAAG Consortium, CARe Consortium, COGENT-BP Consortium, eMERGE Consortium, MEDIA Consortium, MAGIC Consortium, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loci.

Published
2016

102. Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes

Author

Machiela, Mitchell J, Lan, Qing, Slager, Susan L, Vermeulen, Roel CH, Teras, Lauren R, Camp, Nicola J, Cerhan, James R, Spinelli, John J, Wang, Sophia S, Nieters, Alexandra, Vijai, Joseph, Yeager, Meredith, Wang, Zhaoming, Ghesquières, Hervé, McKay, James, Conde, Lucia, de Bakker, Paul IW, Cox, David G, Burdett, Laurie, Monnereau, Alain, Flowers, Christopher R, De Roos, Anneclaire J, Brooks-Wilson, Angela R, Giles, Graham G, Melbye, Mads, Gu, Jian, Jackson, Rebecca D, Kane, Eleanor, Purdue, Mark P, Vajdic, Claire M, Albanes, Demetrius, Kelly, Rachel S, Zucca, Mariagrazia, Bertrand, Kimberly A, Zeleniuch-Jacquotte, Anne, Lawrence, Charles, Hutchinson, Amy, Zhi, Degui, Habermann, Thomas M, Link, Brian K, Novak, Anne J, Dogan, Ahmet, Asmann, Yan W, Liebow, Mark, Thompson, Carrie A, Ansell, Stephen M, Witzig, Thomas E, Tilly, Hervé, Haioun, Corinne, Molina, Thierry J, Hjalgrim, Henrik, Glimelius, Bengt, Adami, Hans-Olov, Roos, Göran, Bracci, Paige M, Riby, Jacques, Smith, Martyn T, Holly, Elizabeth A, Cozen, Wendy, Hartge, Patricia, Morton, Lindsay M, Severson, Richard K, Tinker, Lesley F, North, Kari E, Becker, Nikolaus, Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Foretova, Lenka, Maynadie, Marc, Staines, Anthony, Lightfoot, Tracy, Crouch, Simon, Smith, Alex, Roman, Eve, Diver, W Ryan, Offit, Kenneth, Zelenetz, Andrew, Klein, Robert J, Villano, Danylo J, Zheng, Tongzhang, Zhang, Yawei, Holford, Theodore R, Turner, Jenny, Southey, Melissa C, Clavel, Jacqueline, Virtamo, Jarmo, Weinstein, Stephanie, Riboli, Elio, Vineis, Paolo, Kaaks, Rudolph, Boeing, Heiner, Tjønneland, Anne, Angelucci, Emanuele, Di Lollo, Simonetta, Rais, Marco, De Vivo, Immaculata, Giovannucci, Edward, Kraft, Peter, and Huang, Jinyan

Subjects
Clinical Research, Rare Diseases, Genetics, Cancer, Hematology, Lymphoma, Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Female, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Lymphoma, B-Cell, Male, Middle Aged, Prospective Studies, Telomere, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82,P-value = 8.5 × 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51,P-value = 4.0 × 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.

Published
2016

103. Genome-wide Association Study of Platelet Count Identifies Ancestry-Specific Loci in Hispanic/Latino Americans

Author

Schick, Ursula M, Jain, Deepti, Hodonsky, Chani J, Morrison, Jean V, Davis, James P, Brown, Lisa, Sofer, Tamar, Conomos, Matthew P, Schurmann, Claudia, McHugh, Caitlin P, Nelson, Sarah C, Vadlamudi, Swarooparani, Stilp, Adrienne, Plantinga, Anna, Baier, Leslie, Bien, Stephanie A, Gogarten, Stephanie M, Laurie, Cecelia A, Taylor, Kent D, Liu, Yongmei, Auer, Paul L, Franceschini, Nora, Szpiro, Adam, Rice, Ken, Kerr, Kathleen F, Rotter, Jerome I, Hanson, Robert L, Papanicolaou, George, Rich, Stephen S, Loos, Ruth JF, Browning, Brian L, Browning, Sharon R, Weir, Bruce S, Laurie, Cathy C, Mohlke, Karen L, North, Kari E, Thornton, Timothy A, and Reiner, Alex P

Subjects
Biological Sciences, Genetics, Human Genome, Clinical Research, Hematology, Underpinning research, 1.1 Normal biological development and functioning, Blood, Actinin, Adolescent, Adult, Aged, Alleles, Gene Frequency, Genetic Association Studies, Genetic Loci, Genotype, Genotyping Techniques, Hispanic or Latino, Humans, MEF2 Transcription Factors, Membrane Proteins, Middle Aged, Phenotype, Platelet Count, Polymorphism, Single Nucleotide, Receptors, GABA-B, Young Adult, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Platelets play an essential role in hemostasis and thrombosis. We performed a genome-wide association study of platelet count in 12,491 participants of the Hispanic Community Health Study/Study of Latinos by using a mixed-model method that accounts for admixture and family relationships. We discovered and replicated associations with five genes (ACTN1, ETV7, GABBR1-MOG, MEF2C, and ZBTB9-BAK1). Our strongest association was with Amerindian-specific variant rs117672662 (p value = 1.16 × 10(-28)) in ACTN1, a gene implicated in congenital macrothrombocytopenia. rs117672662 exhibited allelic differences in transcriptional activity and protein binding in hematopoietic cells. Our results underscore the value of diverse populations to extend insights into the allelic architecture of complex traits.

Published
2016

104. Rare Exome Sequence Variants in CLCN6 Reduce Blood Pressure Levels and Hypertension Risk.

Author

Yu, Bing, Pulit, Sara L, Hwang, Shih-Jen, Brody, Jennifer A, Amin, Najaf, Auer, Paul L, Bis, Joshua C, Boerwinkle, Eric, Burke, Gregory L, Chakravarti, Aravinda, Correa, Adolfo, Dreisbach, Albert W, Franco, Oscar H, Ehret, Georg B, Franceschini, Nora, Hofman, Albert, Lin, Dan-Yu, Metcalf, Ginger A, Musani, Solomon K, Muzny, Donna, Palmas, Walter, Raffel, Leslie, Reiner, Alex, Rice, Ken, Rotter, Jerome I, Veeraraghavan, Narayanan, Fox, Ervin, Guo, Xiuqing, North, Kari E, Gibbs, Richard A, van Duijn, Cornelia M, Psaty, Bruce M, Levy, Daniel, Newton-Cheh, Christopher, Morrison, Alanna C, and CHARGE Consortium and the National Heart, Lung, and Blood Institute GO ESP*

Subjects
CHARGE Consortium and the National Heart, Lung, and Blood Institute GO ESP*, Humans, Hypertension, Chloride Channels, Risk Factors, Blood Pressure, Gene Frequency, Alleles, African Continental Ancestry Group, European Continental Ancestry Group, Female, Male, Exome, blood pressure, exome, genetic variation, genome-wide association study, hypertension, CHARGE Consortium and the National Heart, Lung, and Blood Institute GO ESP*, Cardiovascular System & Hematology, Genetics, Cardiorespiratory Medicine and Haematology, Medical Biotechnology
Abstract

BackgroundRare genetic variants influence blood pressure (BP).Methods and resultsWhole-exome sequencing was performed on DNA samples from 17 956 individuals of European ancestry and African ancestry (14 497, first-stage discovery and 3459, second-stage discovery) to examine the effect of rare variants on hypertension and 4 BP traits: systolic BP, diastolic BP, pulse pressure, and mean arterial pressure. Tests of ≈170 000 common variants (minor allele frequency, ≥1%; statistical significance, P≤2.9×10(-7)) and gene-based tests of rare variants (minor allele frequency,

Published
2016

105. Genetic Diversity and Association Studies in US Hispanic/Latino Populations: Applications in the Hispanic Community Health Study/Study of Latinos

Author

Conomos, Matthew P, Laurie, Cecelia A, Stilp, Adrienne M, Gogarten, Stephanie M, McHugh, Caitlin P, Nelson, Sarah C, Sofer, Tamar, Fernández-Rhodes, Lindsay, Justice, Anne E, Graff, Mariaelisa, Young, Kristin L, Seyerle, Amanda A, Avery, Christy L, Taylor, Kent D, Rotter, Jerome I, Talavera, Gregory A, Daviglus, Martha L, Wassertheil-Smoller, Sylvia, Schneiderman, Neil, Heiss, Gerardo, Kaplan, Robert C, Franceschini, Nora, Reiner, Alex P, Shaffer, John R, Barr, R Graham, Kerr, Kathleen F, Browning, Sharon R, Browning, Brian L, Weir, Bruce S, Avilés-Santa, M Larissa, Papanicolaou, George J, Lumley, Thomas, Szpiro, Adam A, North, Kari E, Rice, Ken, Thornton, Timothy A, and Laurie, Cathy C

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Health Disparities, Clinical Research, Human Genome, Minority Health, Generic health relevance, Good Health and Well Being, Genetic Variation, Genome-Wide Association Study, Hispanic or Latino, Humans, United States, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

US Hispanic/Latino individuals are diverse in genetic ancestry, culture, and environmental exposures. Here, we characterized and controlled for this diversity in genome-wide association studies (GWASs) for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We simultaneously estimated population-structure principal components (PCs) robust to familial relatedness and pairwise kinship coefficients (KCs) robust to population structure, admixture, and Hardy-Weinberg departures. The PCs revealed substantial genetic differentiation within and among six self-identified background groups (Cuban, Dominican, Puerto Rican, Mexican, and Central and South American). To control for variation among groups, we developed a multi-dimensional clustering method to define a "genetic-analysis group" variable that retains many properties of self-identified background while achieving substantially greater genetic homogeneity within groups and including participants with non-specific self-identification. In GWASs of 22 biomedical traits, we used a linear mixed model (LMM) including pairwise empirical KCs to account for familial relatedness, PCs for ancestry, and genetic-analysis groups for additional group-associated effects. Including the genetic-analysis group as a covariate accounted for significant trait variation in 8 of 22 traits, even after we fit 20 PCs. Additionally, genetic-analysis groups had significant heterogeneity of residual variance for 20 of 22 traits, and modeling this heteroscedasticity within the LMM reduced genomic inflation for 19 traits. Furthermore, fitting an LMM that utilized a genetic-analysis group rather than a self-identified background group achieved higher power to detect previously reported associations. We expect that the methods applied here will be useful in other studies with multiple ethnic groups, admixture, and relatedness.

Published
2016

106. Mendelian randomization analysis does not support causal associations of birth weight with hypertension risk and blood pressure in adulthood

Author

Zheng, Yan, Huang, Tao, Wang, Tiange, Mei, Zhendong, Sun, Zhonghan, Zhang, Tao, Ellervik, Christina, Chai, Jin-Fang, Sim, Xueling, van Dam, Rob M., Tai, E-Shyong, Koh, Woon-Puay, Dorajoo, Rajkumar, Saw, Seang-Mei, Sabanayagam, Charumathi, Wong, Tien Yin, Gupta, Preeti, Rossing, Peter, Ahluwalia, Tarunveer S., Vinding, Rebecca K., Bisgaard, Hans, Bønnelykke, Klaus, Wang, Yujie, Graff, Mariaelisa, Voortman, Trudy, van Rooij, Frank J. A., Hofman, Albert, van Heemst, Diana, Noordam, Raymond, Estampador, Angela C., Varga, Tibor V., Enzenbach, Cornelia, Scholz, Markus, Thiery, Joachim, Burkhardt, Ralph, Orho-Melander, Marju, Schulz, Christina-Alexandra, Ericson, Ulrika, Sonestedt, Emily, Kubo, Michiaki, Akiyama, Masato, Zhou, Ang, Kilpeläinen, Tuomas O., Hansen, Torben, Kleber, Marcus E., Delgado, Graciela, McCarthy, Mark, Lemaitre, Rozenn N., Felix, Janine F., Jaddoe, Vincent W. V., Wu, Ying, Mohlke, Karen L., Lehtimäki, Terho, Wang, Carol A., Pennell, Craig E., Schunkert, Heribert, Kessler, Thorsten, Zeng, Lingyao, Willenborg, Christina, Peters, Annette, Lieb, Wolfgang, Grote, Veit, Rzehak, Peter, Koletzko, Berthold, Erdmann, Jeanette, Munz, Matthias, Wu, Tangchun, He, Meian, Yu, Caizheng, Lecoeur, Cécile, Froguel, Philippe, Corella, Dolores, Moreno, Luis A., Lai, Chao-Qiang, Pitkänen, Niina, Boreham, Colin A., Ridker, Paul M., Rosendaal, Frits R., de Mutsert, Renée, Power, Chris, Paternoster, Lavinia, Sørensen, Thorkild I. A., Tjønneland, Anne, Overvad, Kim, Djousse, Luc, Rivadeneira, Fernando, Lee, Nanette R., Raitakari, Olli T., Kähönen, Mika, Viikari, Jorma, Langhendries, Jean-Paul, Escribano, Joaquin, Verduci, Elvira, Dedoussis, George, König, Inke, Balkau, Beverley, Coltell, Oscar, Dallongeville, Jean, Meirhaeghe, Aline, Amouyel, Philippe, Gottrand, Frédéric, Pahkala, Katja, Niinikoski, Harri, Hyppönen, Elina, März, Winfried, Mackey, David A., Gruszfeld, Dariusz, Tucker, Katherine L., Fumeron, Frédéric, Estruch, Ramon, Ordovas, Jose M., Arnett, Donna K., Mook-Kanamori, Dennis O., Mozaffarian, Dariush, Psaty, Bruce M., North, Kari E., Chasman, Daniel I., and Qi, Lu

Published
2020
Full Text
View/download PDF

107. 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 1 , 2

Author

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

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Prevention, Diabetes, Genetics, Aging, Cardiovascular, Nutrition, Metabolic and endocrine, Blood Glucose, Cohort Studies, Genetic Association Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Hyperglycemia, Hyperinsulinism, Insulin, Insulin Resistance, Insulin Secretion, Insulin-Secreting Cells, Meat, Meat Products, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, diet, gene–diet interaction, glucose, insulin, meat intake, meta-analysis, Engineering, Medical and Health Sciences, Nutrition & Dietetics, Clinical sciences, Nutrition and dietetics
Abstract

BackgroundRecent 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.ObjectiveWe 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.DesignFourteen 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.ResultsProcessed 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 known to influence fasting glucose or insulin resistance.ConclusionThe association of higher fasting glucose and insulin concentrations with meat consumption was not modified by an index of glucose- and insulin-related single-nucleotide polymorphisms. Six of the participating studies are registered at clinicaltrials.gov as NCT0000513 (Atherosclerosis Risk in Communities), NCT00149435 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetics of Lipid Lowering Drugs and Diet Network), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).

Published
2015

108. A genome-wide association study of marginal zone lymphoma shows association to the HLA region.

Author

Vijai, Joseph, Wang, Zhaoming, Berndt, Sonja I, Skibola, Christine F, Slager, Susan L, de Sanjose, Silvia, Melbye, Mads, Glimelius, Bengt, Bracci, Paige M, Conde, Lucia, Birmann, Brenda M, Wang, Sophia S, Brooks-Wilson, Angela R, Lan, Qing, de Bakker, Paul IW, Vermeulen, Roel CH, Portlock, Carol, Ansell, Stephen M, Link, Brian K, Riby, Jacques, North, Kari E, Gu, Jian, Hjalgrim, Henrik, Cozen, Wendy, Becker, Nikolaus, Teras, Lauren R, Spinelli, John J, Turner, Jenny, Zhang, Yawei, Purdue, Mark P, Giles, Graham G, Kelly, Rachel S, Zeleniuch-Jacquotte, Anne, Ennas, Maria Grazia, Monnereau, Alain, Bertrand, Kimberly A, Albanes, Demetrius, Lightfoot, Tracy, Yeager, Meredith, Chung, Charles C, Burdett, Laurie, Hutchinson, Amy, Lawrence, Charles, Montalvan, Rebecca, Liang, Liming, Huang, Jinyan, Ma, Baoshan, Villano, Danylo J, Maria, Ann, Corines, Marina, Thomas, Tinu, Novak, Anne J, Dogan, Ahmet, Liebow, Mark, Thompson, Carrie A, Witzig, Thomas E, Habermann, Thomas M, Weiner, George J, Smith, Martyn T, Holly, Elizabeth A, Jackson, Rebecca D, Tinker, Lesley F, Ye, Yuanqing, Adami, Hans-Olov, Smedby, Karin E, De Roos, Anneclaire J, Hartge, Patricia, Morton, Lindsay M, Severson, Richard K, Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Foretova, Lenka, Maynadie, Marc, McKay, James, Staines, Anthony, Diver, W Ryan, Vajdic, Claire M, Armstrong, Bruce K, Kricker, Anne, Zheng, Tongzhang, Holford, Theodore R, Severi, Gianluca, Vineis, Paolo, Ferri, Giovanni M, Ricco, Rosalia, Miligi, Lucia, Clavel, Jacqueline, Giovannucci, Edward, Kraft, Peter, Virtamo, Jarmo, Smith, Alex, Kane, Eleanor, Roman, Eve, Chiu, Brian CH, Fraumeni, Joseph F, Wu, Xifeng, Cerhan, James R, Offit, Kenneth, and Chanock, Stephen J

Subjects
Humans, Membrane Glycoproteins, Computational Biology, Major Histocompatibility Complex, Genotype, Polymorphism, Single Nucleotide, European Continental Ancestry Group, Lymphoma, B-Cell, Marginal Zone, Genome-Wide Association Study, Butyrophilins, Polymorphism, Single Nucleotide, Lymphoma, B-Cell, Marginal Zone
Abstract

Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non-Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P=3.95 × 10(-15)) and HLA-B (rs2922994, P=2.43 × 10(-9)) in the HLA region significantly associated with MZL risk. This is the first evidence that genetic variation in the major histocompatibility complex influences MZL susceptibility.

Published
2015

109. Genetic Determinants of Pelvic Organ Prolapse among African American and Hispanic Women in the Women’s Health Initiative

Author

Giri, Ayush, Wu, Jennifer M, Ward, Renee M, Hartmann, Katherine E, Park, Amy J, North, Kari E, Graff, Mariaelisa, Wallace, Robert B, Bareh, Gihan, Qi, Lihong, O'Sullivan, Mary J, Reiner, Alexander P, Edwards, Todd L, and Edwards, Digna R Velez

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Epidemiology, Health Sciences, Reproductive Medicine, Prevention, Contraception/Reproduction, Clinical Research, Human Genome, Reproductive health and childbirth, Black or African American, Aged, Clinical Trials as Topic, Databases, Factual, Female, Gene Frequency, Genetic Loci, Genotyping Techniques, Hispanic or Latino, Humans, Middle Aged, Pelvic Organ Prolapse, Polymorphism, Single Nucleotide, Women's Health, General Science & Technology
Abstract

Current evidence suggests a multifactorial etiology to pelvic organ prolapse (POP), including genetic predisposition. We conducted a genome-wide association study of POP in African American (AA) and Hispanic (HP) women from the Women's Health Initiative Hormone Therapy study. Cases were defined as any POP (grades 1-3) or moderate/severe POP (grades 2-3), while controls had grade 0 POP. We performed race-specific multiple logistic regression analyses between SNPs imputed to 1000 genomes in relation to POP (grade 0 vs 1-3; grade 0 vs 2-3) adjusting for age at diagnosis, body mass index, parity, and genetic ancestry. There were 1274 controls and 1427 cases of any POP and 317 cases of moderate/severe POP. Although none of the analyses reached genome-wide significance (p

Published
2015

110. Demographic and sociocultural risk factors for adulthood weight gain in Hispanic/Latinos: results from the Hispanic Community Health Study / Study of Latinos (HCHS/SOL)

Author

Fernández-Rhodes, Lindsay, Butera, Nicole M., Lodge, Evans K., Franceschini, Nora, Llabre, Maria M., Arredondo, Elva M., Gallo, Linda C., Arguelles, William, Penedo, Frank J., Daviglus, Martha L., Isasi, Carmen R., Smokowski, Paul, Gordon-Larsen, Penny, Aiello, Allison E., Perreira, Krista M., Sotres-Alvarez, Daniela, and North, Kari E.

Published
2021
Full Text
View/download PDF

113. Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

Author

Cerhan, James R, Berndt, Sonja I, Vijai, Joseph, Ghesquières, Hervé, McKay, James, Wang, Sophia S, Wang, Zhaoming, Yeager, Meredith, Conde, Lucia, de Bakker, Paul IW, Nieters, Alexandra, Cox, David, Burdett, Laurie, Monnereau, Alain, Flowers, Christopher R, De Roos, Anneclaire J, Brooks-Wilson, Angela R, Lan, Qing, Severi, Gianluca, Melbye, Mads, Gu, Jian, Jackson, Rebecca D, Kane, Eleanor, Teras, Lauren R, Purdue, Mark P, Vajdic, Claire M, Spinelli, John J, Giles, Graham G, Albanes, Demetrius, Kelly, Rachel S, Zucca, Mariagrazia, Bertrand, Kimberly A, Zeleniuch-Jacquotte, Anne, Lawrence, Charles, Hutchinson, Amy, Zhi, Degui, Habermann, Thomas M, Link, Brian K, Novak, Anne J, Dogan, Ahmet, Asmann, Yan W, Liebow, Mark, Thompson, Carrie A, Ansell, Stephen M, Witzig, Thomas E, Weiner, George J, Veron, Amelie S, Zelenika, Diana, Tilly, Hervé, Haioun, Corinne, Molina, Thierry Jo, Hjalgrim, Henrik, Glimelius, Bengt, Adami, Hans-Olov, Bracci, Paige M, Riby, Jacques, Smith, Martyn T, Holly, Elizabeth A, Cozen, Wendy, Hartge, Patricia, Morton, Lindsay M, Severson, Richard K, Tinker, Lesley F, North, Kari E, Becker, Nikolaus, Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Foretova, Lenka, Maynadie, Marc, Staines, Anthony, Lightfoot, Tracy, Crouch, Simon, Smith, Alex, Roman, Eve, Diver, W Ryan, Offit, Kenneth, Zelenetz, Andrew, Klein, Robert J, Villano, Danylo J, Zheng, Tongzhang, Zhang, Yawei, Holford, Theodore R, Kricker, Anne, Turner, Jenny, Southey, Melissa C, Clavel, Jacqueline, Virtamo, Jarmo, Weinstein, Stephanie, Riboli, Elio, Vineis, Paolo, Kaaks, Rudolph, Trichopoulos, Dimitrios, Vermeulen, Roel CH, Boeing, Heiner, Tjonneland, Anne, Angelucci, Emanuele, Di Lollo, Simonetta, Rais, Marco, and Birmann, Brenda M

Subjects
Human Genome, Rare Diseases, Genetics, Cancer, Hematology, Lymphoma, Aetiology, 2.1 Biological and endogenous factors, Chromosome Mapping, Computational Biology, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Likelihood Functions, Lymphoma, Large B-Cell, Diffuse, Polymorphism, Single Nucleotide, Quantitative Trait Loci, White People, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 × 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 × 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 × 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 × 10(-13) and 3.63 × 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.

Published
2014

114. Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region

Author

Skibola, Christine F, Berndt, Sonja I, Vijai, Joseph, Conde, Lucia, Wang, Zhaoming, Yeager, Meredith, de Bakker, Paul IW, Birmann, Brenda M, Vajdic, Claire M, Foo, Jia-Nee, Bracci, Paige M, Vermeulen, Roel CH, Slager, Susan L, de Sanjose, Silvia, Wang, Sophia S, Linet, Martha S, Salles, Gilles, Lan, Qing, Severi, Gianluca, Hjalgrim, Henrik, Lightfoot, Tracy, Melbye, Mads, Gu, Jian, Ghesquières, Hervé, Link, Brian K, Morton, Lindsay M, Holly, Elizabeth A, Smith, Alex, Tinker, Lesley F, Teras, Lauren R, Kricker, Anne, Becker, Nikolaus, Purdue, Mark P, Spinelli, John J, Zhang, Yawei, Giles, Graham G, Vineis, Paolo, Monnereau, Alain, Bertrand, Kimberly A, Albanes, Demetrius, Zeleniuch-Jacquotte, Anne, Gabbas, Attilio, Chung, Charles C, Burdett, Laurie, Hutchinson, Amy, Lawrence, Charles, Montalvan, Rebecca, Liang, Liming, Huang, Jinyan, Ma, Baoshan, Liu, Jianjun, Adami, Hans-Olov, Glimelius, Bengt, Ye, Yuanqing, Nowakowski, Grzegorz S, Dogan, Ahmet, Thompson, Carrie A, Habermann, Thomas M, Novak, Anne J, Liebow, Mark, Witzig, Thomas E, Weiner, George J, Schenk, Maryjean, Hartge, Patricia, De Roos, Anneclaire J, Cozen, Wendy, Zhi, Degui, Akers, Nicholas K, Riby, Jacques, Smith, Martyn T, Lacher, Mortimer, Villano, Danylo J, Maria, Ann, Roman, Eve, Kane, Eleanor, Jackson, Rebecca D, North, Kari E, Diver, W Ryan, Turner, Jenny, Armstrong, Bruce K, Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Foretova, Lenka, Maynadie, Marc, Staines, Anthony, McKay, James, Brooks-Wilson, Angela R, Zheng, Tongzhang, Holford, Theodore R, Chamosa, Saioa, Kaaks, Rudolph, Kelly, Rachel S, Ohlsson, Bodil, Travis, Ruth C, Weiderpass, Elisabete, Clavel, Jacqueline, Giovannucci, Edward, Kraft, Peter, and Virtamo, Jarmo

Subjects
Hematology, Cancer, Clinical Research, Human Genome, Lymphoma, Genetics, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Alleles, Biomarkers, Tumor, Case-Control Studies, Chromosomes, Human, Genetic Predisposition to Disease, Genome-Wide Association Study, HLA Antigens, Haplotypes, Humans, Lymphoma, Follicular, Polymorphism, Single Nucleotide, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [OR(per-allele)] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (OR(per-allele) = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.

Published
2014

115. Pleiotropic genes for metabolic syndrome and inflammation

Author

Kraja, Aldi T, Chasman, Daniel I, North, Kari E, Reiner, Alexander P, Yanek, Lisa R, Kilpeläinen, Tuomas O, Smith, Jennifer A, Dehghan, Abbas, Dupuis, Josée, Johnson, Andrew D, Feitosa, Mary F, Tekola-Ayele, Fasil, Chu, Audrey Y, Nolte, Ilja M, Dastani, Zari, Morris, Andrew, Pendergrass, Sarah A, Sun, Yan V, Ritchie, Marylyn D, Vaez, Ahmad, Lin, Honghuang, Ligthart, Symen, Marullo, Letizia, Rohde, Rebecca, Shao, Yaming, Ziegler, Mark A, Im, Hae Kyung, Group, Cross Consortia Pleiotropy, Heart and, the Cohorts for, Epidemiology, Aging Research in Genetic, Consortium, the Genetic Investigation of Anthropometric Traits, Consortium, the Global Lipids Genetics, the Meta-Analyses of Glucose, Consortium, Insulin-related traits, Consortium, the Global BPgen, Consortium, The ADIPOGen, Study, the Women's Genome Health, Study, the Howard University Family, Schnabel, Renate B, Jørgensen, Torben, Jørgensen, Marit E, Hansen, Torben, Pedersen, Oluf, Stolk, Ronald P, Snieder, Harold, Hofman, Albert, Uitterlinden, Andre G, Franco, Oscar H, Ikram, M Arfan, Richards, J Brent, Rotimi, Charles, Wilson, James G, Lange, Leslie, Ganesh, Santhi K, Nalls, Mike, Rasmussen-Torvik, Laura J, Pankow, James S, Coresh, Josef, Tang, Weihong, Kao, WH Linda, Boerwinkle, Eric, Morrison, Alanna C, Ridker, Paul M, Becker, Diane M, Rotter, Jerome I, Kardia, Sharon LR, Loos, Ruth JF, Larson, Martin G, Hsu, Yi-Hsiang, Province, Michael A, Tracy, Russell, Voight, Benjamin F, Vaidya, Dhananjay, O'Donnell, Christopher J, Benjamin, Emelia J, Alizadeh, Behrooz Z, Prokopenko, Inga, Meigs, James B, and Borecki, Ingrid B

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Nutrition, Diabetes, Clinical Research, Human Genome, Cardiovascular, Obesity, Prevention, 2.1 Biological and endogenous factors, Biomarkers, Computational Biology, Gene Regulatory Networks, Genetic Pleiotropy, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Inflammation, Meta-Analysis as Topic, Metabolic Syndrome, Phenotype, Quantitative Trait, Heritable, Metabolic syndrome, Inflammatory markers, Pleiotropic associations, Meta-analysis, Regulome, Cross Consortia Pleiotropy Group, Cohorts for Heart and, Aging Research in Genetic Epidemiology, Genetic Investigation of Anthropometric Traits Consortium, Global Lipids Genetics Consortium, Meta-Analyses of Glucose, Insulin-related traits Consortium, Global BPgen Consortium, ADIPOGen Consortium, Women's Genome Health Study, Howard University Family Study, Clinical Sciences, Genetics & Heredity, Clinical sciences
Abstract

Metabolic syndrome (MetS) has become a health and financial burden worldwide. The MetS definition captures clustering of risk factors that predict higher risk for diabetes mellitus and cardiovascular disease. Our study hypothesis is that additional to genes influencing individual MetS risk factors, genetic variants exist that influence MetS and inflammatory markers forming a predisposing MetS genetic network. To test this hypothesis a staged approach was undertaken. (a) We analyzed 17 metabolic and inflammatory traits in more than 85,500 participants from 14 large epidemiological studies within the Cross Consortia Pleiotropy Group. Individuals classified with MetS (NCEP definition), versus those without, showed on average significantly different levels for most inflammatory markers studied. (b) Paired average correlations between 8 metabolic traits and 9 inflammatory markers from the same studies as above, estimated with two methods, and factor analyses on large simulated data, helped in identifying 8 combinations of traits for follow-up in meta-analyses, out of 130,305 possible combinations between metabolic traits and inflammatory markers studied. (c) We performed correlated meta-analyses for 8 metabolic traits and 6 inflammatory markers by using existing GWAS published genetic summary results, with about 2.5 million SNPs from twelve predominantly largest GWAS consortia. These analyses yielded 130 unique SNPs/genes with pleiotropic associations (a SNP/gene associating at least one metabolic trait and one inflammatory marker). Of them twenty-five variants (seven loci newly reported) are proposed as MetS candidates. They map to genes MACF1, KIAA0754, GCKR, GRB14, COBLL1, LOC646736-IRS1, SLC39A8, NELFE, SKIV2L, STK19, TFAP2B, BAZ1B, BCL7B, TBL2, MLXIPL, LPL, TRIB1, ATXN2, HECTD4, PTPN11, ZNF664, PDXDC1, FTO, MC4R and TOMM40. Based on large data evidence, we conclude that inflammation is a feature of MetS and several gene variants show pleiotropic genetic associations across phenotypes and might explain a part of MetS correlated genetic architecture. These findings warrant further functional investigation.

Published
2014

116. Genome-wide association analysis identifies six new loci associated with forced vital capacity

Author

Loth, Daan W, Artigas, María Soler, Gharib, Sina A, Wain, Louise V, Franceschini, Nora, Koch, Beate, Pottinger, Tess D, Smith, Albert Vernon, Duan, Qing, Oldmeadow, Chris, Lee, Mi Kyeong, Strachan, David P, James, Alan L, Huffman, Jennifer E, Vitart, Veronique, Ramasamy, Adaikalavan, Wareham, Nicholas J, Kaprio, Jaakko, Wang, Xin-Qun, Trochet, Holly, Kähönen, Mika, Flexeder, Claudia, Albrecht, Eva, Lopez, Lorna M, de Jong, Kim, Thyagarajan, Bharat, Alves, Alexessander Couto, Enroth, Stefan, Omenaas, Ernst, Joshi, Peter K, Fall, Tove, Viñuela, Ana, Launer, Lenore J, Loehr, Laura R, Fornage, Myriam, Li, Guo, Wilk, Jemma B, Tang, Wenbo, Manichaikul, Ani, Lahousse, Lies, Harris, Tamara B, North, Kari E, Rudnicka, Alicja R, Hui, Jennie, Gu, Xiangjun, Lumley, Thomas, Wright, Alan F, Hastie, Nicholas D, Campbell, Susan, Kumar, Rajesh, Pin, Isabelle, Scott, Robert A, Pietiläinen, Kirsi H, Surakka, Ida, Liu, Yongmei, Holliday, Elizabeth G, Schulz, Holger, Heinrich, Joachim, Davies, Gail, Vonk, Judith M, Wojczynski, Mary, Pouta, Anneli, Johansson, Åsa, Wild, Sarah H, Ingelsson, Erik, Rivadeneira, Fernando, Völzke, Henry, Hysi, Pirro G, Eiriksdottir, Gudny, Morrison, Alanna C, Rotter, Jerome I, Gao, Wei, Postma, Dirkje S, White, Wendy B, Rich, Stephen S, Hofman, Albert, Aspelund, Thor, Couper, David, Smith, Lewis J, Psaty, Bruce M, Lohman, Kurt, Burchard, Esteban G, Uitterlinden, André G, Garcia, Melissa, Joubert, Bonnie R, McArdle, Wendy L, Musk, A Bill, Hansel, Nadia, Heckbert, Susan R, Zgaga, Lina, van Meurs, Joyce BJ, Navarro, Pau, Rudan, Igor, Oh, Yeon-Mok, Redline, Susan, Jarvis, Deborah L, Zhao, Jing Hua, Rantanen, Taina, O'Connor, George T, and Ripatti, Samuli

Subjects
Biological Sciences, Genetics, Human Genome, Rare Diseases, Lung, Cancer, Lung Cancer, Respiratory, Cohort Studies, Databases, Genetic, Follow-Up Studies, Forced Expiratory Volume, Genetic Loci, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Lung Diseases, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Prognosis, Quantitative Trait Loci, Respiratory Function Tests, Spirometry, Vital Capacity, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.

Published
2014

117. Whole-Exome Sequencing Identifies Rare and Low-Frequency Coding Variants Associated with LDL Cholesterol

Author

Lange, Leslie A, Hu, Youna, Zhang, He, Xue, Chenyi, Schmidt, Ellen M, Tang, Zheng-Zheng, Bizon, Chris, Lange, Ethan M, Smith, Joshua D, Turner, Emily H, Jun, Goo, Kang, Hyun Min, Peloso, Gina, Auer, Paul, Li, Kuo-ping, Flannick, Jason, Zhang, Ji, Fuchsberger, Christian, Gaulton, Kyle, Lindgren, Cecilia, Locke, Adam, Manning, Alisa, Sim, Xueling, Rivas, Manuel A, Holmen, Oddgeir L, Gottesman, Omri, Lu, Yingchang, Ruderfer, Douglas, Stahl, Eli A, Duan, Qing, Li, Yun, Durda, Peter, Jiao, Shuo, Isaacs, Aaron, Hofman, Albert, Bis, Joshua C, Correa, Adolfo, Griswold, Michael E, Jakobsdottir, Johanna, Smith, Albert V, Schreiner, Pamela J, Feitosa, Mary F, Zhang, Qunyuan, Huffman, Jennifer E, Crosby, Jacy, Wassel, Christina L, Do, Ron, Franceschini, Nora, Martin, Lisa W, Robinson, Jennifer G, Assimes, Themistocles L, Crosslin, David R, Rosenthal, Elisabeth A, Tsai, Michael, Rieder, Mark J, Farlow, Deborah N, Folsom, Aaron R, Lumley, Thomas, Fox, Ervin R, Carlson, Christopher S, Peters, Ulrike, Jackson, Rebecca D, van Duijn, Cornelia M, Uitterlinden, André G, Levy, Daniel, Rotter, Jerome I, Taylor, Herman A, Gudnason, Vilmundur, Siscovick, David S, Fornage, Myriam, Borecki, Ingrid B, Hayward, Caroline, Rudan, Igor, Chen, Y Eugene, Bottinger, Erwin P, Loos, Ruth JF, Sætrom, Pål, Hveem, Kristian, Boehnke, Michael, Groop, Leif, McCarthy, Mark, Meitinger, Thomas, Ballantyne, Christie M, Gabriel, Stacey B, O’Donnell, Christopher J, Post, Wendy S, North, Kari E, Reiner, Alexander P, Boerwinkle, Eric, Psaty, Bruce M, Altshuler, David, Kathiresan, Sekar, Lin, Dan-Yu, Jarvik, Gail P, Cupples, L Adrienne, Kooperberg, Charles, Wilson, James G, Nickerson, Deborah A, Abecasis, Goncalo R, and Rich, Stephen S

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Prevention, Clinical Research, Heart Disease, Cardiovascular, Atherosclerosis, Aetiology, 2.1 Biological and endogenous factors, Adult, Aged, Apolipoproteins E, Cholesterol, LDL, Cohort Studies, Dyslipidemias, Exome, Female, Follow-Up Studies, Gene Frequency, Genetic Code, Genome-Wide Association Study, Genotype, Humans, Lipase, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Proprotein Convertase 9, Proprotein Convertases, Receptors, LDL, Sequence Analysis, DNA, Serine Endopeptidases, NHLBI Grand Opportunity Exome Sequencing Project, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or

Published
2014

118. Large-Scale Genome-Wide Association Studies and Meta-Analyses of Longitudinal Change in Adult Lung Function

Author

Tang, Wenbo, Kowgier, Matthew, Loth, Daan W, Soler Artigas, María, Joubert, Bonnie R, Hodge, Emily, Gharib, Sina A, Smith, Albert V, Ruczinski, Ingo, Gudnason, Vilmundur, Mathias, Rasika A, Harris, Tamara B, Hansel, Nadia N, Launer, Lenore J, Barnes, Kathleen C, Hansen, Joyanna G, Albrecht, Eva, Aldrich, Melinda C, Allerhand, Michael, Barr, R Graham, Brusselle, Guy G, Couper, David J, Curjuric, Ivan, Davies, Gail, Deary, Ian J, Dupuis, Josée, Fall, Tove, Foy, Millennia, Franceschini, Nora, Gao, Wei, Gläser, Sven, Gu, Xiangjun, Hancock, Dana B, Heinrich, Joachim, Hofman, Albert, Imboden, Medea, Ingelsson, Erik, James, Alan, Karrasch, Stefan, Koch, Beate, Kritchevsky, Stephen B, Kumar, Ashish, Lahousse, Lies, Li, Guo, Lind, Lars, Lindgren, Cecilia, Liu, Yongmei, Lohman, Kurt, Lumley, Thomas, McArdle, Wendy L, Meibohm, Bernd, Morris, Andrew P, Morrison, Alanna C, Musk, Bill, North, Kari E, Palmer, Lyle J, Probst-Hensch, Nicole M, Psaty, Bruce M, Rivadeneira, Fernando, Rotter, Jerome I, Schulz, Holger, Smith, Lewis J, Sood, Akshay, Starr, John M, Strachan, David P, Teumer, Alexander, Uitterlinden, André G, Völzke, Henry, Voorman, Arend, Wain, Louise V, Wells, Martin T, Wilk, Jemma B, Williams, O Dale, Heckbert, Susan R, Stricker, Bruno H, London, Stephanie J, Fornage, Myriam, Tobin, Martin D, O'Connor, George T, Hall, Ian P, and Cassano, Patricia A

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Chronic Obstructive Pulmonary Disease, Human Genome, Lung, Clinical Research, Prevention, Respiratory, Adult, Chromosomes, Human, Pair 11, Female, Gene Expression Regulation, Genetic Loci, Genome-Wide Association Study, Humans, Longitudinal Studies, Male, Respiration, General Science & Technology
Abstract

BackgroundGenome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function.MethodsWe performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis.ResultsThe overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively.ConclusionsIn this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function.

Published
2014

120. Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci

Author

de las Fuentes, Lisa, primary, Schwander, Karen L., additional, Brown, Michael R., additional, Bentley, Amy R., additional, Winkler, Thomas W., additional, Sung, Yun Ju, additional, Munroe, Patricia B., additional, Miller, Clint L., additional, Aschard, Hugo, additional, Aslibekyan, Stella, additional, Bartz, Traci M., additional, Bielak, Lawrence F., additional, Chai, Jin Fang, additional, Cheng, Ching-Yu, additional, Dorajoo, Rajkumar, additional, Feitosa, Mary F., additional, Guo, Xiuqing, additional, Hartwig, Fernando P., additional, Horimoto, Andrea, additional, Kolčić, Ivana, additional, Lim, Elise, additional, Liu, Yongmei, additional, Manning, Alisa K., additional, Marten, Jonathan, additional, Musani, Solomon K., additional, Noordam, Raymond, additional, Padmanabhan, Sandosh, additional, Rankinen, Tuomo, additional, Richard, Melissa A., additional, Ridker, Paul M., additional, Smith, Albert V., additional, Vojinovic, Dina, additional, Zonderman, Alan B., additional, Alver, Maris, additional, Boissel, Mathilde, additional, Christensen, Kaare, additional, Freedman, Barry I., additional, Gao, Chuan, additional, Giulianini, Franco, additional, Harris, Sarah E., additional, He, Meian, additional, Hsu, Fang-Chi, additional, Kühnel, Brigitte, additional, Laguzzi, Federica, additional, Li, Xiaoyin, additional, Lyytikäinen, Leo-Pekka, additional, Nolte, Ilja M., additional, Poveda, Alaitz, additional, Rauramaa, Rainer, additional, Riaz, Muhammad, additional, Robino, Antonietta, additional, Sofer, Tamar, additional, Takeuchi, Fumihiko, additional, Tayo, Bamidele O., additional, van der Most, Peter J., additional, Verweij, Niek, additional, Ware, Erin B., additional, Weiss, Stefan, additional, Wen, Wanqing, additional, Yanek, Lisa R., additional, Zhan, Yiqiang, additional, Amin, Najaf, additional, Arking, Dan E., additional, Ballantyne, Christie, additional, Boerwinkle, Eric, additional, Brody, Jennifer A., additional, Broeckel, Ulrich, additional, Campbell, Archie, additional, Canouil, Mickaël, additional, Chai, Xiaoran, additional, Chen, Yii-Der Ida, additional, Chen, Xu, additional, Chitrala, Kumaraswamy Naidu, additional, Concas, Maria Pina, additional, de Faire, Ulf, additional, de Mutsert, Renée, additional, de Silva, H. Janaka, additional, de Vries, Paul S., additional, Do, Ahn, additional, Faul, Jessica D., additional, Fisher, Virginia, additional, Floyd, James S., additional, Forrester, Terrence, additional, Friedlander, Yechiel, additional, Girotto, Giorgia, additional, Gu, C. Charles, additional, Hallmans, Göran, additional, Heikkinen, Sami, additional, Heng, Chew-Kiat, additional, Homuth, Georg, additional, Hunt, Steven, additional, Ikram, M. Arfan, additional, Jacobs, David R., additional, Kavousi, Maryam, additional, Khor, Chiea Chuen, additional, Kilpeläinen, Tuomas O., additional, Koh, Woon-Puay, additional, Komulainen, Pirjo, additional, Langefeld, Carl D., additional, Liang, Jingjing, additional, Liu, Kiang, additional, Liu, Jianjun, additional, Lohman, Kurt, additional, Mägi, Reedik, additional, Manichaikul, Ani W., additional, McKenzie, Colin A., additional, Meitinger, Thomas, additional, Milaneschi, Yuri, additional, Nauck, Matthias, additional, Nelson, Christopher P., additional, O’Connell, Jeffrey R., additional, Palmer, Nicholette D., additional, Pereira, Alexandre C., additional, Perls, Thomas, additional, Peters, Annette, additional, Polašek, Ozren, additional, Raitakari, Olli T., additional, Rice, Kenneth, additional, Rice, Treva K., additional, Rich, Stephen S., additional, Sabanayagam, Charumathi, additional, Schreiner, Pamela J., additional, Shu, Xiao-Ou, additional, Sidney, Stephen, additional, Sims, Mario, additional, Smith, Jennifer A., additional, Starr, John M., additional, Strauch, Konstantin, additional, Tai, E. Shyong, additional, Taylor, Kent D., additional, Tsai, Michael Y., additional, Uitterlinden, André G., additional, van Heemst, Diana, additional, Waldenberger, Melanie, additional, Wang, Ya-Xing, additional, Wei, Wen-Bin, additional, Wilson, Gregory, additional, Xuan, Deng, additional, Yao, Jie, additional, Yu, Caizheng, additional, Yuan, Jian-Min, additional, Zhao, Wei, additional, Becker, Diane M., additional, Bonnefond, Amélie, additional, Bowden, Donald W., additional, Cooper, Richard S., additional, Deary, Ian J., additional, Divers, Jasmin, additional, Esko, Tõnu, additional, Franks, Paul W., additional, Froguel, Philippe, additional, Gieger, Christian, additional, Jonas, Jost B., additional, Kato, Norihiro, additional, Lakka, Timo A., additional, Leander, Karin, additional, Lehtimäki, Terho, additional, Magnusson, Patrik K. E., additional, North, Kari E., additional, Ntalla, Ioanna, additional, Penninx, Brenda, additional, Samani, Nilesh J., additional, Snieder, Harold, additional, Spedicati, Beatrice, additional, van der Harst, Pim, additional, Völzke, Henry, additional, Wagenknecht, Lynne E., additional, Weir, David R., additional, Wojczynski, Mary K., additional, Wu, Tangchun, additional, Zheng, Wei, additional, Zhu, Xiaofeng, additional, Bouchard, Claude, additional, Chasman, Daniel I., additional, Evans, Michele K., additional, Fox, Ervin R., additional, Gudnason, Vilmundur, additional, Hayward, Caroline, additional, Horta, Bernardo L., additional, Kardia, Sharon L. R., additional, Krieger, Jose Eduardo, additional, Mook-Kanamori, Dennis O., additional, Peyser, Patricia A., additional, Province, Michael M., additional, Psaty, Bruce M., additional, Rudan, Igor, additional, Sim, Xueling, additional, Smith, Blair H., additional, van Dam, Rob M., additional, van Duijn, Cornelia M., additional, Wong, Tien Yin, additional, Arnett, Donna K., additional, Rao, Dabeeru C., additional, Gauderman, James, additional, Liu, Ching-Ti, additional, Morrison, Alanna C., additional, Rotter, Jerome I., additional, and Fornage, Myriam, additional

Published
2023
Full Text
View/download PDF

121. SMIM1 absence is associated with reduced energy expenditure and excess weight

Author

Banasik, Karina, Bay, Jakob, Boldsen, Jens Kjærgaard, Brodersen, Thorsten, Brunak, Søren, Burgdorf, Kristoffer, Chalmer, Mona Ameri, Didriksen, Maria, Dinh, Khoa Manh, Dowsett, Joseph, Erikstrup, Christian, Feenstra, Bjarke, Geller, Frank, Gudbjartsson, Daniel, Hansen, Thomas Folkmann, Hindhede, Lotte, Hjalgrim, Henrik, Jacobsen, Rikke Louise, Jemec, Gregor, Jensen, Bitten Aagaard, Kaspersen, Katrine, Kjerulff, Bertram Dalskov, Kogelman, Lisette, Hørup Larsen, Margit Anita, Louloudis, Ioannis, Lundgaard, Agnete, Susan, Mikkelsen, Christina, Nissen, Ioanna, Nyegaard, Mette, Ostrowski, Sisse Rye, Pedersen, Ole Birger, Henriksen, Alexander Pil, Rohde, Palle Duun, Rostgaard, Klaus, Schwinn, Michael, Stefansson, Kari, Stefánsson, Hreinn, Sørensen, Erik, þorsteinsdóttir, Unnur, Thørner, Lise Wegner, Bruun, Mie Topholm, Ullum, Henrik, Werge, Thomas, Westergaard, David, Chen, Ji, Spracklen, Cassandra N., Marenne, Gaëlle, Varshney, Arushi, Corbin, Laura J., Luan, Jian’an, Willems, Sara M., Wu, Ying, Zhang, Xiaoshuai, Horikoshi, Momoko, Boutin, Thibaud S., Mägi, Reedik, Waage, Johannes, Li-Gao, Ruifang, Katie Chan, Kei Hang, Yao, Jie, Anasanti, Mila D., Chu, Audrey Y., Claringbould, Annique, Heikkinen, Jani, Hong, Jaeyoung, Hottenga, Jouke-Jan, Huo, Shaofeng, Kaakinen, Marika A., Louie, Tin, März, Winfried, Moreno-Macias, Hortensia, Ndungu, Anne, Nelson, Sarah C., Nolte, Ilja M., North, Kari E., Raulerson, Chelsea K., Ray, Debashree, Rohde, Rebecca, Rybin, Denis, Schurmann, Claudia, Sim, Xueling, Southam, Loz, Stewart, Isobel D., Wang, Carol A., Wang, Yujie, Wu, Peitao, Zhang, Weihua, Ahluwalia, Tarunveer S., Appel, Emil V.R., Bielak, Lawrence F., Brody, Jennifer A., Burtt, Noël P., Cabrera, Claudia P., Cade, Brian E., Chai, Jin Fang, Chai, Xiaoran, Chang, Li-Ching, Chen, Chien-Hsiun, Chen, Brian H., Chitrala, Kumaraswamy Naidu, Chiu, Yen-Feng, de Haan, Hugoline G., Delgado, Graciela E., Demirkan, Ayse, Duan, Qing, Engmann, Jorgen, Fatumo, Segun A., Gayán, Javier, Giulianini, Franco, Gong, Jung Ho, Gustafsson, Stefan, Hai, Yang, Hartwig, Fernando P., He, Jing, Heianza, Yoriko, Huang, Tao, Huerta-Chagoya, Alicia, Hwang, Mi Yeong, Jensen, Richard A., Kawaguchi, Takahisa, Kentistou, Katherine A., Kim, Young Jin, Kleber, Marcus E., Kooner, Ishminder K., Lai, Shuiqing, Lange, Leslie A., Langefeld, Carl D., Lauzon, Marie, Li, Man, Ligthart, Symen, Liu, Jun, Loh, Marie, Long, Jirong, Lyssenko, Valeriya, Mangino, Massimo, Marzi, Carola, Montasser, May E., Nag, Abhishek, Nakatochi, Masahiro, Noce, Damia, Noordam, Raymond, Pistis, Giorgio, Preuss, Michael, Raffield, Laura, Rasmussen-Torvik, Laura J., Rich, Stephen S., Robertson, Neil R., Rueedi, Rico, Ryan, Kathleen, Sanna, Serena, Saxena, Richa, Schraut, Katharina E., Sennblad, Bengt, Setoh, Kazuya, Smith, Albert V., Southam, Lorraine, Sparsø, Thomas, Strawbridge, Rona J., Takeuchi, Fumihiko, Tan, Jingyi, Trompet, Stella, van den Akker, Erik, van der Most, Peter J., Verweij, Niek, Vogel, Mandy, Wang, Heming, Wang, Chaolong, Wang, Nan, Warren, Helen R., Wen, Wanqing, Wilsgaard, Tom, Wong, Andrew, Wood, Andrew R., Xie, Tian, Zafarmand, Mohammad Hadi, Zhao, Jing-Hua, Zhao, Wei, Amin, Najaf, Arzumanyan, Zorayr, Astrup, Arne, Bakker, Stephan J.L., Baldassarre, Damiano, Beekman, Marian, Bergman, Richard N., Bertoni, Alain, Blüher, Matthias, Bonnycastle, Lori L., Bornstein, Stefan R., Bowden, Donald W., Cai, Qiuyin, Campbell, Archie, Campbell, Harry, Chang, Yi Cheng, de Geus, Eco J.C., Dehghan, Abbas, Du, Shufa, Eiriksdottir, Gudny, Farmaki, Aliki Eleni, Frånberg, Mattias, Fuchsberger, Christian, Gao, Yutang, Gjesing, Anette P., Goel, Anuj, Han, Sohee, Hartman, Catharina A., Herder, Christian, Hicks, Andrew A., Hsieh, Chang-Hsun, Hsueh, Willa A., Ichihara, Sahoko, Igase, Michiya, Ikram, M. Arfan, Johnson, W. Craig, Jørgensen, Marit E., Joshi, Peter K., Kalyani, Rita R., Kandeel, Fouad R., Katsuya, Tomohiro, Khor, Chiea Chuen, Kiess, Wieland, Kolcic, Ivana, Kuulasmaa, Teemu, Kuusisto, Johanna, Läll, Kristi, Lam, Kelvin, Lawlor, Deborah A., Lee, Nanette R., Lemaitre, Rozenn N., Li, Honglan, Lin, Shih-Yi, Lindström, Jaana, Linneberg, Allan, Liu, Jianjun, Lorenzo, Carlos, Matsubara, Tatsuaki, Matsuda, Fumihiko, Mingrone, Geltrude, Mooijaart, Simon, Moon, Sanghoon, Nabika, Toru, Nadkarni, Girish N., Nadler, Jerry L., Nelis, Mari, Neville, Matt J., Norris, Jill M., Ohyagi, Yasumasa, Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Qi, Qibin, Raven, Dennis, Reilly, Dermot F., Reiner, Alex, Rivideneira, Fernando, Roll, Kathryn, Rudan, Igor, Sabanayagam, Charumathi, Sandow, Kevin, Sattar, Naveed, Schürmann, Annette, Shi, Jinxiu, Stringham, Heather M., Taylor, Kent D., Teslovich, Tanya M., Thuesen, Betina, Timmers, Paul R.H.J., Tremoli, Elena, Tsai, Michael Y., Uitterlinden, Andre, van Dam, Rob M., van Heemst, Diana, van Hylckama Vlieg, Astrid, Van Vliet-Ostaptchouk, Jana V., Vangipurapu, Jagadish, Vestergaard, Henrik, Wang, Tao, Willems van Dijk, Ko, Zemunik, Tatijana, Abecasis, Goncalo R., Adair, Linda S., Aguilar-Salinas, Carlos Alberto, Alarcón-Riquelme, Marta E., An, Ping, Aviles-Santa, Larissa, Becker, Diane M., Beilin, Lawrence J., Bergmann, Sven, Bisgaard, Hans, Black, Corri, Boehnke, Michael, Boerwinkle, Eric, Böhm, Bernhard O., Bønnelykke, Klaus, Boomsma, D.I., Bottinger, Erwin P., Buchanan, Thomas A., Canouil, Mickaël, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Ida Chen, Yii-Der, Cheng, Ching-Yu, Collins, Francis S., Correa, Adolfo, Cucca, Francesco, Janaka de Silva, H., Dedoussis, George, Elmståhl, Sölve, Evans, Michele K., Ferrannini, Ele, Ferrucci, Luigi, Florez, Jose C., Franks, Paul W., Frayling, Timothy M., Froguel, Philippe, Gigante, Bruna, Goodarzi, Mark O., Gordon-Larsen, Penny, Grallert, Harald, Grarup, Niels, Grimsgaard, Sameline, Groop, Leif, Gudnason, Vilmundur, Guo, Xiuqing, Hamsten, Anders, Hansen, Torben, Hayward, Caroline, Heckbert, Susan R., Horta, Bernardo L., Huang, Wei, Ingelsson, Erik, James, Pankow S., Jarvelin, Marjo-Ritta, Jonas, Jost B., Jukema, J. Wouter, Kaleebu, Pontiano, Kaplan, Robert, Kardia, Sharon L.R., Kato, Norihiro, Keinanen-Kiukaanniemi, Sirkka M., Kim, Bong-Jo, Kivimaki, Mika, Koistinen, Heikki A., Kooner, Jaspal S., Körner, Antje, Kovacs, Peter, Kuh, Diana, Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lakka, Timo A., Launer, Lenore J., Leander, Karin, Li, Huaixing, Lin, Xu, Lind, Lars, Lindgren, Cecilia, Liu, Simin, Loos, Ruth J.F., Magnusson, Patrik K.E., Mahajan, Anubha, Metspalu, Andres, Mook-Kanamori, Dennis O., Mori, Trevor A., Munroe, Patricia B., Njølstad, Inger, O'Connell, Jeffrey R., Oldehinkel, Albertine J., Ong, Ken K., Padmanabhan, Sandosh, Palmer, Colin N.A., Palmer, Nicholette D., Pedersen, Oluf, Pennell, Craig E., Porteous, David J., Pramstaller, Peter P., Province, Michael A., Psaty, Bruce M., Qi, Lu, Raffel, Leslie J., Rauramaa, Rainer, Redline, Susan, Ridker, Paul M., Rosendaal, Frits R., Saaristo, Timo E., Sandhu, Manjinder, Saramies, Jouko, Schneiderman, Neil, Schwarz, Peter, Scott, Laura J., Selvin, Elizabeth, Sever, Peter, Shu, Xiao-Ou, Slagboom, P. Eline, Small, Kerrin S., Smith, Blair H., Snieder, Harold, Sofer, Tamar, Sørensen, Thorkild I.A., Spector, Tim D., Stanton, Alice, Steves, Claire J., Stumvoll, Michael, Sun, Liang, Tabara, Yasuharu, Tai, E. Shyong, Timpson, Nicholas J., Tönjes, Anke, Tuomilehto, Jaakko, Tusie, Teresa, Uusitupa, Matti, van der Harst, Pim, van Duijn, Cornelia, Vitart, Veronique, Vollenweider, Peter, Vrijkotte, Tanja G.M., Wagenknecht, Lynne E., Walker, Mark, Wang, Ya X., Wareham, Nick J., Watanabe, Richard M., Watkins, Hugh, Wei, Wen B., Wickremasinghe, Ananda R., Willemsen, Gonneke, Wilson, James F., Wong, Tien-Yin, Wu, Jer-Yuarn, Xiang, Anny H., Yanek, Lisa R., Yengo, Loïc, Yokota, Mitsuhiro, Zeggini, Eleftheria, Zheng, Wei, Zonderman, Alan B., Rotter, Jerome I., Gloyn, Anna L., McCarthy, Mark I., Dupuis, Josée, Meigs, James B., Scott, Robert A., Prokopenko, Inga, Leong, Aaron, Liu, Ching-Ti, Parker, Stephen C.J., Mohlke, Karen L., Langenberg, Claudia, Wheeler, Eleanor, Morris, Andrew P., Barroso, Inês, Stefanucci, Luca, Moslemi, Camous, Tomé, Ana R., Virtue, Samuel, Bidault, Guillaume, Gleadall, Nicholas S., Watson, Laura P.E., Kwa, Jing E., Burden, Frances, Farrow, Samantha, Võsa, Urmo, Burling, Keith, Walker, Lindsay, Ord, John, Barker, Peter, Warner, James, Frary, Amy, Renhstrom, Karola, Ashford, Sofie E., Piper, Jo, Biggs, Gail, Erber, Wendy N., Hoffman, Gary J., Schoenmakers, Nadia, Rieneck, Klaus, Dziegiel, Morten H., Azzu, Vian, Vacca, Michele, Aparicio, Hugo Javier, Hui, Qin, Cho, Kelly, Sun, Yan V., Wilson, Peter W., Bayraktar, Omer A., Vidal-Puig, Antonio, Ostrowski, Sisse R., Astle, William J., Olsson, Martin L., Storry, Jill R., Pedersen, Ole B., Ouwehand, Willem H., Chatterjee, Krishna, Vuckovic, Dragana, and Frontini, Mattia

Published
2024
Full Text
View/download PDF

122. Strengthening Causal Inference in Exposomics Research: Application of Genetic Data and Methods

Author

Avery, Christy L., Howard, Annie Green, Ballou, Anna F., Buchanan, Victoria L., Collins, Jason M., Downie, Carolina G., Engel, Stephanie M., Graff, Mariaelisa, Highland, Heather M., Lee, Moa P., Lilly, Adam G., Lu, Kun, Rager, Julia E., Staley, Brooke S., North, Kari E., and Gordon-Larsen, Penny

Subjects
Environmental health -- Genetic aspects, Toxicogenomics -- Research, Medical research -- Methods, Medicine, Experimental -- Methods, Environmental issues, Health
Abstract

Summary: Advances in technologies to measure a broad set of exposures have led to a range of exposome research efforts. Yet, these efforts have insufficiently integrated methods that incorporate genetic data to strengthen causal inference, despite evidence that many exposome-associated phenotypes are heritable. Objective: We demonstrate how integration of methods and study designs that incorporate genetic data can strengthen causal inference in exposomics research by helping address six challenges: reverse causation and unmeasured confounding, comprehensive examination of phenotypic effects, low efficiency, replication, multilevel data integration, and characterization of tissue-specific effects. Examples are drawn from studies of biomarkers and health behaviors, exposure domains where the causal inference methods we describe are most often applied. Discussion: Technological, computational, and statistical advances in genotyping, imputation, and analysis, combined with broad data sharing and cross-study collaborations, offer multiple opportunities to strengthen causal inference in exposomics research. Full application of these opportunities will require an expanded understanding of genetic variants that predict exposome phenotypes as well as an appreciation that the utility of genetic variants for causal inference will vary by exposure and may depend on large sample sizes. However, several of these challenges can be addressed through international scientific collaborations that prioritize data sharing. Ultimately, we anticipate that efforts to better integrate methods that incorporate genetic data will extend the reach of exposomics research by helping address the challenges of comprehensively measuring the exposome and its health effects across studies, the life course, and in varied contexts and diverse populations. https://doi.org/10.1289/EHP9098, Introduction The past decade has witnessed a paradigm shift in the environmental sciences as studies have shifted from examining specific exposures to attempting to comprehensively measure and characterize the broad [...]

Published
2022
Full Text
View/download PDF

124. Genetic variants associated with fasting glucose and insulin concentrations in an ethnically diverse population: results from the Population Architecture using Genomics and Epidemiology (PAGE) study

Author

Fesinmeyer, Megan D, Meigs, James B, North, Kari E, Schumacher, Fredrick R, Bůžková, Petra, Franceschini, Nora, Haessler, Jeffrey, Goodloe, Robert, Spencer, Kylee L, Voruganti, Venkata, Howard, Barbara V, Jackson, Rebecca, Kolonel, Laurence N, Liu, Simin, Manson, JoAnn E, Monroe, Kristine R, Mukamal, Kenneth, Dilks, Holli H, Pendergrass, Sarah A, Nato, Andrew, Wan, Peggy, Wilkens, Lynne R, Marchand, Loic, Ambite, José, Buyske, Steven, Florez, Jose C, Crawford, Dana C, Hindorff, Lucia A, Haiman, Christopher A, Peters, Ulrike, and Pankow, James S

Abstract

Abstract Background Multiple genome-wide association studies (GWAS) within European populations have implicated common genetic variants associated with insulin and glucose concentrations. In contrast, few studies have been conducted within minority groups, which carry the highest burden of impaired glucose homeostasis and type 2 diabetes in the U.S. Methods As part of the 'Population Architecture using Genomics and Epidemiology (PAGE) Consortium, we investigated the association of up to 10 GWAS-identified single nucleotide polymorphisms (SNPs) in 8 genetic regions with glucose or insulin concentrations in up to 36,579 non-diabetic subjects including 23,323 European Americans (EA) and 7,526 African Americans (AA), 3,140 Hispanics, 1,779 American Indians (AI), and 811 Asians. We estimated the association between each SNP and fasting glucose or log-transformed fasting insulin, followed by meta-analysis to combine results across PAGE sites. Results Overall, our results show that 9/9 GWAS SNPs are associated with glucose in EA (p = 0.04 to 9 × 10-15), versus 3/9 in AA (p= 0.03 to 6 × 10-5), 3/4 SNPs in Hispanics, 2/4 SNPs in AI, and 1/2 SNPs in Asians. For insulin we observed a significant association with rs780094/GCKR in EA, Hispanics and AI only. Conclusions Generalization of results across multiple racial/ethnic groups helps confirm the relevance of some of these loci for glucose and insulin metabolism. Lack of association in non-EA groups may be due to insufficient power, or to unique patterns of linkage disequilibrium.

Published
2013

125. Heritability and Preliminary Genome-Wide Linkage Analysis of Arsenic Metabolites in Urine

Author

Tellez-Plaza, Maria, Gribble, Matthew O, Voruganti, V Saroja, Francesconi, Kevin A, Goessler, Walter, Umans, Jason G, Silbergeld, Ellen K, Guallar, Eliseo, Franceschini, Nora, North, Kari E, Kao, Wen H, MacCluer, Jean W, Cole, Shelley A, and Navas-Acien, Ana

Subjects
Epidemiology, Health Sciences, Genetics, Clinical Research, Foodborne Illness, American Indian or Alaska Native, Aged, Arsenic, Female, Genetic Linkage, Genome-Wide Association Study, Humans, Life Style, Male, Middle Aged, American Indians, arsenic metabolism, arsenic species, determinants, heritability, linkage scan, Strong Heart Study, Environmental Sciences, Medical and Health Sciences, Toxicology, Biomedical and clinical sciences, Environmental sciences, Health sciences
Abstract

BackgroundArsenic (III) methyltransferase (AS3MT) has been related to urine arsenic metabolites in association studies. Other genes might also play roles in arsenic metabolism and excretion.ObjectiveWe evaluated genetic determinants of urine arsenic metabolites in American Indian adults from the Strong Heart Study (SHS).MethodsWe evaluated heritability of urine arsenic metabolites [percent inorganic arsenic (%iAs), percent monomethylarsonate (%MMA), and percent dimethylarsinate (%DMA)] in 2,907 SHS participants with urine arsenic measurements and at least one relative within the cohort. We conducted a preliminary linkage analysis in a subset of 487 participants with available genotypes on approximately 400 short tandem repeat markers using a general pedigree variance component approach for localizing quantitative trait loci (QTL).ResultsThe medians (interquartile ranges) for %iAs, %MMA, and %DMA were 7.7% (5.4-10.7%), 13.6% (10.5-17.1%), and 78.4% (72.5-83.1%), respectively. The estimated heritability was 53% for %iAs, 50% for %MMA, and 59% for %DMA. After adjustment for sex, age, smoking, body mass index, alcohol consumption, region, and total urine arsenic concentrations, LOD [logarithm (to the base of 10) of the odds] scores indicated suggestive evidence for genetic linkage with QTLs influencing urine arsenic metabolites on chromosomes 5 (LOD = 2.03 for %iAs), 9 (LOD = 2.05 for %iAs and 2.10 for %MMA), and 11 (LOD = 1.94 for %iAs). A peak for %DMA on chromosome 10 within 2 Mb of AS3MT had an LOD of 1.80.ConclusionsThis population-based family study in American Indian communities supports a genetic contribution to variation in the distribution of arsenic metabolites in urine and, potentially, the involvement of genes other than AS3MT.

Published
2013

126. A systematic mapping approach of 16q12.2/FTO and BMI in more than 20,000 African Americans narrows in on the underlying functional variation: results from the Population Architecture using Genomics and Epidemiology (PAGE) study.

Author

Peters, Ulrike, North, Kari E, Sethupathy, Praveen, Buyske, Steve, Haessler, Jeff, Jiao, Shuo, Fesinmeyer, Megan D, Jackson, Rebecca D, Kuller, Lew H, Rajkovic, Aleksandar, Lim, Unhee, Cheng, Iona, Schumacher, Fred, Wilkens, Lynne, Li, Rongling, Monda, Keri, Ehret, Georg, Nguyen, Khanh-Dung H, Cooper, Richard, Lewis, Cora E, Leppert, Mark, Irvin, Marguerite R, Gu, C Charles, Houston, Denise, Buzkova, Petra, Ritchie, Marylyn, Matise, Tara C, Le Marchand, Loic, Hindorff, Lucia A, Crawford, Dana C, Haiman, Christopher A, and Kooperberg, Charles

Subjects
Humans, Obesity, Genetic Predisposition to Disease, Adaptor Proteins, Signal Transducing, Proteins, Body Mass Index, Chromosome Mapping, Linkage Disequilibrium, Alleles, Adult, Aged, Aged, 80 and over, Middle Aged, Continental Population Groups, African Americans, European Continental Ancestry Group, Female, Male, Genome-Wide Association Study, Metagenomics, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Adaptor Proteins, Signal Transducing, and over, Genetics, Developmental Biology
Abstract

Genetic variants in intron 1 of the fat mass- and obesity-associated (FTO) gene have been consistently associated with body mass index (BMI) in Europeans. However, follow-up studies in African Americans (AA) have shown no support for some of the most consistently BMI-associated FTO index single nucleotide polymorphisms (SNPs). This is most likely explained by different race-specific linkage disequilibrium (LD) patterns and lower correlation overall in AA, which provides the opportunity to fine-map this region and narrow in on the functional variant. To comprehensively explore the 16q12.2/FTO locus and to search for second independent signals in the broader region, we fine-mapped a 646-kb region, encompassing the large FTO gene and the flanking gene RPGRIP1L by investigating a total of 3,756 variants (1,529 genotyped and 2,227 imputed variants) in 20,488 AAs across five studies. We observed associations between BMI and variants in the known FTO intron 1 locus: the SNP with the most significant p-value, rs56137030 (8.3 × 10(-6)) had not been highlighted in previous studies. While rs56137030was correlated at r(2)>0.5 with 103 SNPs in Europeans (including the GWAS index SNPs), this number was reduced to 28 SNPs in AA. Among rs56137030 and the 28 correlated SNPs, six were located within candidate intronic regulatory elements, including rs1421085, for which we predicted allele-specific binding affinity for the transcription factor CUX1, which has recently been implicated in the regulation of FTO. We did not find strong evidence for a second independent signal in the broader region. In summary, this large fine-mapping study in AA has substantially reduced the number of common alleles that are likely to be functional candidates of the known FTO locus. Importantly our study demonstrated that comprehensive fine-mapping in AA provides a powerful approach to narrow in on the functional candidate(s) underlying the initial GWAS findings in European populations.

Published
2013

127. Genome-wide association of body fat distribution in African ancestry populations suggests new loci.

Author

Liu, Ching-Ti, Monda, Keri L, Taylor, Kira C, Lange, Leslie, Demerath, Ellen W, Palmas, Walter, Wojczynski, Mary K, Ellis, Jaclyn C, Vitolins, Mara Z, Liu, Simin, Papanicolaou, George J, Irvin, Marguerite R, Xue, Luting, Griffin, Paula J, Nalls, Michael A, Adeyemo, Adebowale, Liu, Jiankang, Li, Guo, Ruiz-Narvaez, Edward A, Chen, Wei-Min, Chen, Fang, Henderson, Brian E, Millikan, Robert C, Ambrosone, Christine B, Strom, Sara S, Guo, Xiuqing, Andrews, Jeanette S, Sun, Yan V, Mosley, Thomas H, Yanek, Lisa R, Shriner, Daniel, Haritunians, Talin, Rotter, Jerome I, Speliotes, Elizabeth K, Smith, Megan, Rosenberg, Lynn, Mychaleckyj, Josyf, Nayak, Uma, Spruill, Ida, Garvey, W Timothy, Pettaway, Curtis, Nyante, Sarah, Bandera, Elisa V, Britton, Angela F, Zonderman, Alan B, Rasmussen-Torvik, Laura J, Chen, Yii-Der Ida, Ding, Jingzhong, Lohman, Kurt, Kritchevsky, Stephen B, Zhao, Wei, Peyser, Patricia A, Kardia, Sharon LR, Kabagambe, Edmond, Broeckel, Ulrich, Chen, Guanjie, Zhou, Jie, Wassertheil-Smoller, Sylvia, Neuhouser, Marian L, Rampersaud, Evadnie, Psaty, Bruce, Kooperberg, Charles, Manson, Joann E, Kuller, Lewis H, Ochs-Balcom, Heather M, Johnson, Karen C, Sucheston, Lara, Ordovas, Jose M, Palmer, Julie R, Haiman, Christopher A, McKnight, Barbara, Howard, Barbara V, Becker, Diane M, Bielak, Lawrence F, Liu, Yongmei, Allison, Matthew A, Grant, Struan FA, Burke, Gregory L, Patel, Sanjay R, Schreiner, Pamela J, Borecki, Ingrid B, Evans, Michele K, Taylor, Herman, Sale, Michele M, Howard, Virginia, Carlson, Christopher S, Rotimi, Charles N, Cushman, Mary, Harris, Tamara B, Reiner, Alexander P, Cupples, L Adrienne, North, Kari E, and Fox, Caroline S

Subjects
Humans, Obesity, Waist-Hip Ratio, Polymorphism, Single Nucleotide, African Continental Ancestry Group, European Continental Ancestry Group, Female, Male, Adiposity, Body Fat Distribution, Genome-Wide Association Study, Genetic Loci, Polymorphism, Single Nucleotide, Developmental Biology, Genetics
Abstract

Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values

Published
2013

128. Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution

Author

Justice, Anne E., Karaderi, Tugce, Highland, Heather M., Young, Kristin L., Graff, Mariaelisa, Lu, Yingchang, Turcot, Valérie, Auer, Paul L., Fine, Rebecca S., Guo, Xiuqing, Schurmann, Claudia, Lempradl, Adelheid, Marouli, Eirini, Mahajan, Anubha, Winkler, Thomas W., Locke, Adam E., Medina-Gomez, Carolina, Esko, Tõnu, Vedantam, Sailaja, Giri, Ayush, Lo, Ken Sin, Alfred, Tamuno, Mudgal, Poorva, Ng, Maggie C. Y., Heard-Costa, Nancy L., Feitosa, Mary F., Manning, Alisa K., Willems, Sara M., Sivapalaratnam, Suthesh, Abecasis, Goncalo, Alam, Dewan S., Allison, Matthew, Amouyel, Philippe, Arzumanyan, Zorayr, Balkau, Beverley, Bastarache, Lisa, Bergmann, Sven, Bielak, Lawrence F., Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A., Bork-Jensen, Jette, Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Broer, Linda, Burt, Amber A., Butterworth, Adam S., Caulfield, Mark J., Cesana, Giancarlo, Chambers, John C., Chasman, Daniel I., Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Collins, Francis S., Cook, James P., Cox, Amanda J., Crosslin, David S., Danesh, John, de Bakker, Paul I. W., Denus, Simon de, Mutsert, Renée de, Dedoussis, George, Demerath, Ellen W., Dennis, Joe G., Denny, Josh C., Di Angelantonio, Emanuele, Dörr, Marcus, Drenos, Fotios, Dubé, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Fornage, Myriam, Fox, Caroline S., Franks, Paul W., Friedrich, Nele, Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Girotto, Giorgia, Gorski, Mathias, Grallert, Harald, Grarup, Niels, Grove, Megan L., Gustafsson, Stefan, Haessler, Jeff, Hansen, Torben, Hattersley, Andrew T., Hayward, Caroline, Heid, Iris M., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hu, Yao, Hung, Yi-Jen, Hveem, Kristian, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jarvik, Gail P., Jia, Yucheng, Jørgensen, Torben, Jousilahti, Pekka, Justesen, Johanne M., Kahali, Bratati, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kee, Frank, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kovacs, Peter, Krämer, Bernhard K., Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, Lange, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lee, Wen-Jane, Lehtimäki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Li-An, Lin, Xu, Lind, Lars, Lindström, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Luan, Jian’an, Lyytikäinen, Leo-Pekka, MacGregor, Stuart, Mägi, Reedik, Männistö, Satu, Marenne, Gaëlle, Marten, Jonathan, Masca, Nicholas G. D., McCarthy, Mark I., Meidtner, Karina, Mihailov, Evelin, Moilanen, Leena, Moitry, Marie, Mook-Kanamori, Dennis O., Morgan, Anna, Morris, Andrew P., Müller-Nurasyid, Martina, Munroe, Patricia B., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Ntalla, Ioanna, O’Connell, Jeffrey R., Owen, Katharine R., Pedersen, Oluf, Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R. B., Pers, Tune H., Ewing, Ailith, Polasek, Ozren, Raitakari, Olli T., Rasheed, Asif, Raulerson, Chelsea K., Rauramaa, Rainer, Reilly, Dermot F., Reiner, Alex P., Ridker, Paul M., Rivas, Manuel A., Robertson, Neil R., Robino, Antonietta, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo, Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Blair H., Smith, Jennifer A., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swart, Karin M. A., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Tönjes, Anke, Torres, Mina, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Uitterlinden, André G., Uusitupa, Matti, van Duijn, Cornelia M., Vanhala, Mauno, Varma, Rohit, Vermeulen, Sita H., Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wareham, Nicholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zheng, He, Zhou, Wei, Zillikens, M. Carola, Rivadeneira, Fernando, Borecki, Ingrid B., Pospisilik, J. Andrew, Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, Mohlke, Karen L., Rotter, Jerome I., Kutalik, Zoltán, Hirschhorn, Joel N., Cupples, L. Adrienne, Loos, Ruth J. F., North, Kari E., and Lindgren, Cecilia M.

Published
2019
Full Text
View/download PDF

129. No Interactions Between Previously Associated 2-Hour Glucose Gene Variants and Physical Activity or BMI on 2-Hour Glucose Levels

Author

Scott, Robert A, Chu, Audrey Y, Grarup, Niels, Manning, Alisa K, Hivert, Marie-France, Shungin, Dmitry, Tönjes, Anke, Yesupriya, Ajay, Barnes, Daniel, Bouatia-Naji, Nabila, Glazer, Nicole L, Jackson, Anne U, Kutalik, Zoltán, Lagou, Vasiliki, Marek, Diana, Rasmussen-Torvik, Laura J, Stringham, Heather M, Tanaka, Toshiko, Aadahl, Mette, Arking, Dan E, Bergmann, Sven, Boerwinkle, Eric, Bonnycastle, Lori L, Bornstein, Stefan R, Brunner, Eric, Bumpstead, Suzannah J, Brage, Soren, Carlson, Olga D, Chen, Han, Chen, Yii-Der Ida, Chines, Peter S, Collins, Francis S, Couper, David J, Dennison, Elaine M, Dowling, Nicole F, Egan, Josephine S, Ekelund, Ulf, Erdos, Michael R, Forouhi, Nita G, Fox, Caroline S, Goodarzi, Mark O, Grässler, Jürgen, Gustafsson, Stefan, Hallmans, Göran, Hansen, Torben, Hingorani, Aroon, Holloway, John W, Hu, Frank B, Isomaa, Bo, Jameson, Karen A, Johansson, Ingegerd, Jonsson, Anna, Jørgensen, Torben, Kivimaki, Mika, Kovacs, Peter, Kumari, Meena, Kuusisto, Johanna, Laakso, Markku, Lecoeur, Cécile, Lévy-Marchal, Claire, Li, Guo, Loos, Ruth JF, Lyssenko, Valeri, Marmot, Michael, Marques-Vidal, Pedro, Morken, Mario A, Müller, Gabriele, North, Kari E, Pankow, James S, Payne, Felicity, Prokopenko, Inga, Psaty, Bruce M, Renström, Frida, Rice, Ken, Rotter, Jerome I, Rybin, Denis, Sandholt, Camilla H, Sayer, Avan A, Shrader, Peter, Schwarz, Peter EH, Siscovick, David S, Stančáková, Alena, Stumvoll, Michael, Teslovich, Tanya M, Waeber, Gérard, Williams, Gordon H, Witte, Daniel R, Wood, Andrew R, Xie, Weijia, Boehnke, Michael, Cooper, Cyrus, Ferrucci, Luigi, Froguel, Philippe, Groop, Leif, Kao, WH Linda, Vollenweider, Peter, Walker, Mark, Watanabe, Richard M, Pedersen, Oluf, and Meigs, James B

Subjects
Biomedical and Clinical Sciences, Clinical Research, Genetics, Diabetes, Prevention, Obesity, Nutrition, 2.1 Biological and endogenous factors, Aetiology, 2.3 Psychological, social and economic factors, Metabolic and endocrine, Blood Glucose, Body Mass Index, Epigenesis, Genetic, Gene Expression Regulation, Genotype, Humans, Life Style, Motor Activity, Polymorphism, Single Nucleotide, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences
Abstract

Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥ 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.

Published
2012

130. Fine-mapping and initial characterization of QT interval loci in African Americans.

Author

Avery, Christy L, Sethupathy, Praveen, Buyske, Steven, He, Qianchuan, Lin, Dan-Yu, Arking, Dan E, Carty, Cara L, Duggan, David, Fesinmeyer, Megan D, Hindorff, Lucia A, Jeff, Janina M, Klein, Liviu, Patton, Kristen K, Peters, Ulrike, Shohet, Ralph V, Sotoodehnia, Nona, Young, Alicia M, Kooperberg, Charles, Haiman, Christopher A, Mohlke, Karen L, Whitsel, Eric A, and North, Kari E

Subjects
Humans, Tachycardia, Genetic Predisposition to Disease, Electrocardiography, Risk Factors, Computational Biology, Quantitative Trait, Heritable, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Aged, Middle Aged, African Americans, European Continental Ancestry Group, United States, Female, Male, Genome-Wide Association Study, Metagenomics, Quantitative Trait, Heritable, Polymorphism, Single Nucleotide, Clinical Research, Heart Disease, Human Genome, Genetics, Cardiovascular, Developmental Biology
Abstract

The QT interval (QT) is heritable and its prolongation is a risk factor for ventricular tachyarrhythmias and sudden death. Most genetic studies of QT have examined European ancestral populations; however, the increased genetic diversity in African Americans provides opportunities to narrow association signals and identify population-specific variants. We therefore evaluated 6,670 SNPs spanning eleven previously identified QT loci in 8,644 African American participants from two Population Architecture using Genomics and Epidemiology (PAGE) studies: the Atherosclerosis Risk in Communities study and Women's Health Initiative Clinical Trial. Of the fifteen known independent QT variants at the eleven previously identified loci, six were significantly associated with QT in African American populations (P≤1.20×10(-4)): ATP1B1, PLN1, KCNQ1, NDRG4, and two NOS1AP independent signals. We also identified three population-specific signals significantly associated with QT in African Americans (P≤1.37×10(-5)): one at NOS1AP and two at ATP1B1. Linkage disequilibrium (LD) patterns in African Americans assisted in narrowing the region likely to contain the functional variants for several loci. For example, African American LD patterns showed that 0 SNPs were in LD with NOS1AP signal rs12143842, compared with European LD patterns that indicated 87 SNPs, which spanned 114.2 Kb, were in LD with rs12143842. Finally, bioinformatic-based characterization of the nine African American signals pointed to functional candidates located exclusively within non-coding regions, including predicted binding sites for transcription factors such as TBX5, which has been implicated in cardiac structure and conductance. In this detailed evaluation of QT loci, we identified several African Americans SNPs that better define the association with QT and successfully narrowed intervals surrounding established loci. These results demonstrate that the same loci influence variation in QT across multiple populations, that novel signals exist in African Americans, and that the SNPs identified as strong candidates for functional evaluation implicate gene regulatory dysfunction in QT prolongation.

Published
2012

131. A Bivariate Genome-Wide Approach to Metabolic Syndrome STAMPEED Consortium

Author

Kraja, Aldi T, Vaidya, Dhananjay, Pankow, James S, Goodarzi, Mark O, Assimes, Themistocles L, Kullo, Iftikhar J, Sovio, Ulla, Mathias, Rasika A, Sun, Yan V, Franceschini, Nora, Absher, Devin, Li, Guo, Zhang, Qunyuan, Feitosa, Mary F, Glazer, Nicole L, Haritunians, Talin, Hartikainen, Anna-Liisa, Knowles, Joshua W, North, Kari E, Iribarren, Carlos, Kral, Brian, Yanek, Lisa, O’Reilly, Paul F, McCarthy, Mark I, Jaquish, Cashell, Couper, David J, Chakravarti, Aravinda, Psaty, Bruce M, Becker, Lewis C, Province, Michael A, Boerwinkle, Eric, Quertermous, Thomas, Palotie, Leena, Jarvelin, Marjo-Riitta, Becker, Diane M, Kardia, Sharon LR, Rotter, Jerome I, Chen, Yii-Der Ida, and Borecki, Ingrid B

Subjects
Biomedical and Clinical Sciences, Nutrition, Human Genome, Clinical Research, Cardiovascular, Diabetes, Obesity, Genetics, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Adult, Aged, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Meta-Analysis as Topic, Metabolic Syndrome, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences
Abstract

OBJECTIVE The metabolic syndrome (MetS) is defined as concomitant disorders of lipid and glucose metabolism, central obesity, and high blood pressure, with an increased risk of type 2 diabetes and cardiovascular disease. This study tests whether common genetic variants with pleiotropic effects account for some of the correlated architecture among five metabolic phenotypes that define MetS. RESEARCH DESIGN AND METHODS Seven studies of the STAMPEED consortium, comprising 22,161 participants of European ancestry, underwent genome-wide association analyses of metabolic traits using a panel of ∼2.5 million imputed single nucleotide polymorphisms (SNPs). Phenotypes were defined by the National Cholesterol Education Program (NCEP) criteria for MetS in pairwise combinations. Individuals exceeding the NCEP thresholds for both traits of a pair were considered affected. RESULTS Twenty-nine common variants were associated with MetS or a pair of traits. Variants in the genes LPL, CETP, APOA5 (and its cluster), GCKR (and its cluster), LIPC, TRIB1, LOC100128354/MTNR1B, ABCB11, and LOC100129150 were further tested for their association with individual qualitative and quantitative traits. None of the 16 top SNPs (one per gene) associated simultaneously with more than two individual traits. Of them 11 variants showed nominal associations with MetS per se. The effects of 16 top SNPs on the quantitative traits were relatively small, together explaining from ∼9% of the variance in triglycerides, 5.8% of high-density lipoprotein cholesterol, 3.6% of fasting glucose, and 1.4% of systolic blood pressure. CONCLUSIONS Qualitative and quantitative pleiotropic tests on pairs of traits indicate that a small portion of the covariation in these traits can be explained by the reported common genetic variants.

Published
2011

132. Ancestral diversity in lipoprotein(a) studies helps address evidence gaps

Author

Lee, Moa P, primary, Dimos, Sofia F, additional, Raffield, Laura M, additional, Wang, Zhe, additional, Ballou, Anna F, additional, Downie, Carolina G, additional, Arehart, Christopher H, additional, Correa, Adolfo, additional, de Vries, Paul S, additional, Du, Zhaohui, additional, Gignoux, Christopher R, additional, Gordon-Larsen, Penny, additional, Guo, Xiuqing, additional, Haessler, Jeffrey, additional, Howard, Annie Green, additional, Hu, Yao, additional, Kassahun, Helina, additional, Kent, Shia T, additional, Lopez, J Antonio G, additional, Monda, Keri L, additional, North, Kari E, additional, Peters, Ulrike, additional, Preuss, Michael H, additional, Rich, Stephen S, additional, Rhodes, Shannon L, additional, Yao, Jie, additional, Yarosh, Rina, additional, Tsai, Michael Y, additional, Rotter, Jerome I, additional, Kooperberg, Charles L, additional, Loos, Ruth J F, additional, Ballantyne, Christie, additional, Avery, Christy L, additional, and Graff, Mariaelisa, additional

Published
2023
Full Text
View/download PDF

133. Ancestry-specific associations identified in genome-wide combined-phenotype study of red blood cell traits emphasize benefits of diversity in genomics

Author

Hodonsky, Chani J., Baldassari, Antoine R., Bien, Stephanie A., Raffield, Laura M., Highland, Heather M., Sitlani, Colleen M., Wojcik, Genevieve L., Tao, Ran, Graff, Marielisa, Tang, Weihong, Thyagarajan, Bharat, Buyske, Steve, Fornage, Myriam, Hindorff, Lucia A., Li, Yun, Lin, Danyu, Reiner, Alex P., North, Kari E., Loos, Ruth J. F., Kooperberg, Charles, and Avery, Christy L.

Published
2020
Full Text
View/download PDF

135. Protocols, Methods, and Tools for Genome-Wide Association Studies (GWAS) of Dental Traits

Author

Agler, Cary S., primary, Shungin, Dmitry, additional, Ferreira Zandoná, Andrea G., additional, Schmadeke, Paige, additional, Basta, Patricia V., additional, Luo, Jason, additional, Cantrell, John, additional, Pahel, Thomas D., additional, Meyer, Beau D., additional, Shaffer, John R., additional, Schaefer, Arne S., additional, North, Kari E., additional, and Divaris, Kimon, additional

Published
2019
Full Text
View/download PDF

137. Sugar-sweetened beverage intake associations with fasting glucose and insulin concentrations are not modified by selected genetic variants in a ChREBP-FGF21 pathway: a meta-analysis

Author

McKeown, Nicola M., Dashti, Hassan S., Ma, Jiantao, Haslam, Danielle E., Kiefte-de Jong, Jessica C., Smith, Caren E., Tanaka, Toshiko, Graff, Mariaelisa, Lemaitre, Rozenn N., Rybin, Denis, Sonestedt, Emily, Frazier-Wood, Alexis C., Mook-Kanamori, Dennis O., Li, Yanping, Wang, Carol A., Leermakers, Elisabeth T. M., Mikkilä, Vera, Young, Kristin L., Mukamal, Kenneth J., Cupples, L. Adrienne, Schulz, Christina-Alexandra, Chen, Tzu-An, Li-Gao, Ruifang, Huang, Tao, Oddy, Wendy H., Raitakari, Olli, Rice, Kenneth, Meigs, James B., Ericson, Ulrika, Steffen, Lyn M., Rosendaal, Frits R., Hofman, Albert, Kähönen, Mika, Psaty, Bruce M., Brunkwall, Louise, Uitterlinden, Andre G., Viikari, Jorma, Siscovick, David S., Seppälä, Ilkka, North, Kari E., Mozaffarian, Dariush, Dupuis, Josée, Orho-Melander, Marju, Rich, Stephen S., de Mutsert, Renée, Qi, Lu, Pennell, Craig E., Franco, Oscar H., Lehtimäki, Terho, and Herman, Mark A.

Published
2018
Full Text
View/download PDF

138. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Author

Turcot, Valérie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G. D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C. Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Gonçalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Brumat, Marco, Burt, Amber A., Butterworth, Adam S., Campbell, Peter T., Cappellani, Stefania, Carey, David J., Catamo, Eulalia, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der I., Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Corominas Galbany, Jordi, Cox, Amanda J., Crosslin, David S., Cuellar-Partida, Gabriel, D’Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I. W., Groot, Mark C. H., Mutsert, Renée, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., Heijer, Martin, Hollander, Anneke I., Ruijter, Hester M., Dennis, Joe G., Denny, Josh C., Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dubé, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Edwards, Todd L., Ellinghaus, David, Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Farooqi, I. Sadaf, Faul, Jessica D., Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Franke, Andre, Franks, Paul W., Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P., Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans-Jörgen, Grant, Struan F. A., Grarup, Niels, Griffiths, Helen L., Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R., Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Have, Christian T., Hayward, Caroline, He, Liang, Heard-Costa, Nancy L., Heath, Andrew C., Heid, Iris M., Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hu, Yao, Huang, Paul L., Huffman, Jennifer E., Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan-Håkan, Jarvik, Gail P., Jensen, Gorm B., Jia, Yucheng, Johansson, Stefan, Jørgensen, Marit E., Jørgensen, Torben, Jukema, J. Wouter, Kahali, Bratati, Kahn, René S., Kähönen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A., Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltán, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lehtimäki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng-Hung, Lin, Li-An, Lin, Xu, Lind, Lars, Lindström, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Liu, Yongmei, Lo, Ken S., Lophatananon, Artitaya, Lotery, Andrew J., Loukola, Anu, Luan, Jian’an, Lubitz, Steven A., Lyytikäinen, Leo-Pekka, Männistö, Satu, Marenne, Gaëlle, Mazul, Angela L., McCarthy, Mark I., McKean-Cowdin, Roberta, Medland, Sarah E., Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L., Moilanen, Leena, Moitry, Marie, Montgomery, Grant W., Mook-Kanamori, Dennis O., Moore, Carmel, Mori, Trevor A., Morris, Andrew D., Morris, Andrew P., Müller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njølstad, Pål R., Nordestgaard, Børge G., Nyholt, Dale R., O’Connel, Jeffrey R., O’Donoghue, Michelle L., Olde Loohuis, Loes M., Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Palmer, Nicholette D., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R. B., Pers, Tune H., Person, Thomas N., Peters, Annette, Petersen, Eva R. B., Peyser, Patricia A., Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J., Puolijoki, Hannu, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Renström, Frida, Rheinberger, Myriam, Ridker, Paul M., Rioux, John D., Rivas, Manuel A., Roberts, David J., Robertson, Neil R., Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati H., Sheu, Wayne H.-H., Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Albert V., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J., Tada, Hayato, Tansey, Katherine E., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, André G., Uusitupa, Matti, Laan, Sander W., Duijn, Cornelia M., Leeuwen, Nienke, van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Velez Edwards, Digna R., Vermeulen, Sita H., Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Völker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Ware, Erin B., Wareham, Nicholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Witte, Daniel R., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhao, Wei, Zhou, Wei, Zondervan, Krina T, Rotter, Jerome I., Pospisilik, John A., Rivadeneira, Fernando, Borecki, Ingrid B., Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, North, Kari E., Lindgren, Cecilia M., Hirschhorn, Joel N., and Loos, Ruth J. F.

Published
2018
Full Text
View/download PDF

139. Correction: Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes

Author

Berndt, Sonja I, Vijai, Joseph, Benavente, Yolanda, Camp, Nicola J, Nieters, Alexandra, Wang, Zhaoming, Smedby, Karin E, Kleinstern, Geffen, Hjalgrim, Henrik, Besson, Caroline, Skibola, Christine F, Morton, Lindsay M, Brooks-Wilson, Angela R, Teras, Lauren R, Breeze, Charles, Arias, Joshua, Adami, Hans-Olov, Albanes, Demetrius, Anderson, Kenneth C, Ansell, Stephen M, Bassig, Bryan, Becker, Nikolaus, Bhatti, Parveen, Birmann, Brenda M, Boffetta, Paolo, Bracci, Paige M, Brennan, Paul, Brown, Elizabeth E, Burdett, Laurie, Cannon-Albright, Lisa A, Chang, Ellen T, Chiu, Brian C H, Chung, Charles C, Clavel, Jacqueline, Cocco, Pierluigi, Colditz, Graham, Conde, Lucia, Conti, David V, Cox, David G, Curtin, Karen, Casabonne, Delphine, De Vivo, Immaculata, Diepstra, Arjan, Diver, W Ryan, Dogan, Ahmet, Edlund, Christopher K, Foretova, Lenka, Fraumeni, Joseph F, Gabbas, Attilio, Ghesquières, Hervé, Giles, Graham G, Glaser, Sally, Glenn, Martha, Glimelius, Bengt, Gu, Jian, Habermann, Thomas M, Haiman, Christopher A, Haioun, Corinne, Hofmann, Jonathan N, Holford, Theodore R, Holly, Elizabeth A, Hutchinson, Amy, Izhar, Aalin, Jackson, Rebecca D, Jarrett, Ruth F, Kaaks, Rudolph, Kane, Eleanor, Kolonel, Laurence N, Kong, Yinfei, Kraft, Peter, Kricker, Anne, Lake, Annette, Lan, Qing, Lawrence, Charles, Li, Dalin, Liebow, Mark, Link, Brian K, Magnani, Corrado, Maynadie, Marc, McKay, James, Melbye, Mads, Miligi, Lucia, Milne, Roger L, Molina, Thierry J, Monnereau, Alain, Montalvan, Rebecca, North, Kari E, Novak, Anne J, Onel, Kenan, Purdue, Mark P, Rand, Kristin A, Riboli, Elio, Riby, Jacques, Roman, Eve, Salles, Gilles, Sborov, Douglas W, Severson, Richard K, Shanafelt, Tait D, Smith, Martyn T, Smith, Alexandra, Song, Kevin W, Song, Lei, Southey, Melissa C, Spinelli, John J, Staines, Anthony, Stephens, Deborah, Sutherland, Heather J, Tkachuk, Kaitlyn, Thompson, Carrie A, Tilly, Hervé, Tinker, Lesley F, Travis, Ruth C, Turner, Jenny, Vachon, Celine M, Vajdic, Claire M, Van Den Berg, Anke, Van Den Berg, David J, Vermeulen, Roel C H, Vineis, Paolo, Wang, Sophia S, Weiderpass, Elisabete, Weiner, George J, Weinstein, Stephanie, Doo, Nicole Wong, Ye, Yuanqing, Yeager, Meredith, Yu, Kai, Zeleniuch-Jacquotte, Anne, Zhang, Yawei, Zheng, Tongzhang, Ziv, Elad, Sampson, Joshua, Chatterjee, Nilanjan, Offit, Kenneth, Cozen, Wendy, Wu, Xifeng, Cerhan, James R, Chanock, Stephen J, Slager, Susan L, Rothman, Nathaniel, Berndt, Sonja I, Vijai, Joseph, Benavente, Yolanda, Camp, Nicola J, Nieters, Alexandra, Wang, Zhaoming, Smedby, Karin E, Kleinstern, Geffen, Hjalgrim, Henrik, Besson, Caroline, Skibola, Christine F, Morton, Lindsay M, Brooks-Wilson, Angela R, Teras, Lauren R, Breeze, Charles, Arias, Joshua, Adami, Hans-Olov, Albanes, Demetrius, Anderson, Kenneth C, Ansell, Stephen M, Bassig, Bryan, Becker, Nikolaus, Bhatti, Parveen, Birmann, Brenda M, Boffetta, Paolo, Bracci, Paige M, Brennan, Paul, Brown, Elizabeth E, Burdett, Laurie, Cannon-Albright, Lisa A, Chang, Ellen T, Chiu, Brian C H, Chung, Charles C, Clavel, Jacqueline, Cocco, Pierluigi, Colditz, Graham, Conde, Lucia, Conti, David V, Cox, David G, Curtin, Karen, Casabonne, Delphine, De Vivo, Immaculata, Diepstra, Arjan, Diver, W Ryan, Dogan, Ahmet, Edlund, Christopher K, Foretova, Lenka, Fraumeni, Joseph F, Gabbas, Attilio, Ghesquières, Hervé, Giles, Graham G, Glaser, Sally, Glenn, Martha, Glimelius, Bengt, Gu, Jian, Habermann, Thomas M, Haiman, Christopher A, Haioun, Corinne, Hofmann, Jonathan N, Holford, Theodore R, Holly, Elizabeth A, Hutchinson, Amy, Izhar, Aalin, Jackson, Rebecca D, Jarrett, Ruth F, Kaaks, Rudolph, Kane, Eleanor, Kolonel, Laurence N, Kong, Yinfei, Kraft, Peter, Kricker, Anne, Lake, Annette, Lan, Qing, Lawrence, Charles, Li, Dalin, Liebow, Mark, Link, Brian K, Magnani, Corrado, Maynadie, Marc, McKay, James, Melbye, Mads, Miligi, Lucia, Milne, Roger L, Molina, Thierry J, Monnereau, Alain, Montalvan, Rebecca, North, Kari E, Novak, Anne J, Onel, Kenan, Purdue, Mark P, Rand, Kristin A, Riboli, Elio, Riby, Jacques, Roman, Eve, Salles, Gilles, Sborov, Douglas W, Severson, Richard K, Shanafelt, Tait D, Smith, Martyn T, Smith, Alexandra, Song, Kevin W, Song, Lei, Southey, Melissa C, Spinelli, John J, Staines, Anthony, Stephens, Deborah, Sutherland, Heather J, Tkachuk, Kaitlyn, Thompson, Carrie A, Tilly, Hervé, Tinker, Lesley F, Travis, Ruth C, Turner, Jenny, Vachon, Celine M, Vajdic, Claire M, Van Den Berg, Anke, Van Den Berg, David J, Vermeulen, Roel C H, Vineis, Paolo, Wang, Sophia S, Weiderpass, Elisabete, Weiner, George J, Weinstein, Stephanie, Doo, Nicole Wong, Ye, Yuanqing, Yeager, Meredith, Yu, Kai, Zeleniuch-Jacquotte, Anne, Zhang, Yawei, Zheng, Tongzhang, Ziv, Elad, Sampson, Joshua, Chatterjee, Nilanjan, Offit, Kenneth, Cozen, Wendy, Wu, Xifeng, Cerhan, James R, Chanock, Stephen J, Slager, Susan L, and Rothman, Nathaniel

Abstract

Correction to: Leukemia https://doi.org/10.1038/s41375-022-01711-0, published online 22 October 2022

Published
2023

140. Correction: Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes

Author

IRAS OH Epidemiology Chemical Agents, IRAS – One Health Chemical, Berndt, Sonja I, Vijai, Joseph, Benavente, Yolanda, Camp, Nicola J, Nieters, Alexandra, Wang, Zhaoming, Smedby, Karin E, Kleinstern, Geffen, Hjalgrim, Henrik, Besson, Caroline, Skibola, Christine F, Morton, Lindsay M, Brooks-Wilson, Angela R, Teras, Lauren R, Breeze, Charles, Arias, Joshua, Adami, Hans-Olov, Albanes, Demetrius, Anderson, Kenneth C, Ansell, Stephen M, Bassig, Bryan, Becker, Nikolaus, Bhatti, Parveen, Birmann, Brenda M, Boffetta, Paolo, Bracci, Paige M, Brennan, Paul, Brown, Elizabeth E, Burdett, Laurie, Cannon-Albright, Lisa A, Chang, Ellen T, Chiu, Brian C H, Chung, Charles C, Clavel, Jacqueline, Cocco, Pierluigi, Colditz, Graham, Conde, Lucia, Conti, David V, Cox, David G, Curtin, Karen, Casabonne, Delphine, De Vivo, Immaculata, Diepstra, Arjan, Diver, W Ryan, Dogan, Ahmet, Edlund, Christopher K, Foretova, Lenka, Fraumeni, Joseph F, Gabbas, Attilio, Ghesquières, Hervé, Giles, Graham G, Glaser, Sally, Glenn, Martha, Glimelius, Bengt, Gu, Jian, Habermann, Thomas M, Haiman, Christopher A, Haioun, Corinne, Hofmann, Jonathan N, Holford, Theodore R, Holly, Elizabeth A, Hutchinson, Amy, Izhar, Aalin, Jackson, Rebecca D, Jarrett, Ruth F, Kaaks, Rudolph, Kane, Eleanor, Kolonel, Laurence N, Kong, Yinfei, Kraft, Peter, Kricker, Anne, Lake, Annette, Lan, Qing, Lawrence, Charles, Li, Dalin, Liebow, Mark, Link, Brian K, Magnani, Corrado, Maynadie, Marc, McKay, James, Melbye, Mads, Miligi, Lucia, Milne, Roger L, Molina, Thierry J, Monnereau, Alain, Montalvan, Rebecca, North, Kari E, Novak, Anne J, Onel, Kenan, Purdue, Mark P, Rand, Kristin A, Riboli, Elio, Riby, Jacques, Roman, Eve, Salles, Gilles, Sborov, Douglas W, Severson, Richard K, Shanafelt, Tait D, Smith, Martyn T, Smith, Alexandra, Song, Kevin W, Song, Lei, Southey, Melissa C, Spinelli, John J, Staines, Anthony, Stephens, Deborah, Sutherland, Heather J, Tkachuk, Kaitlyn, Thompson, Carrie A, Tilly, Hervé, Tinker, Lesley F, Travis, Ruth C, Turner, Jenny, Vachon, Celine M, Vajdic, Claire M, Van Den Berg, Anke, Van Den Berg, David J, Vermeulen, Roel C H, Vineis, Paolo, Wang, Sophia S, Weiderpass, Elisabete, Weiner, George J, Weinstein, Stephanie, Doo, Nicole Wong, Ye, Yuanqing, Yeager, Meredith, Yu, Kai, Zeleniuch-Jacquotte, Anne, Zhang, Yawei, Zheng, Tongzhang, Ziv, Elad, Sampson, Joshua, Chatterjee, Nilanjan, Offit, Kenneth, Cozen, Wendy, Wu, Xifeng, Cerhan, James R, Chanock, Stephen J, Slager, Susan L, Rothman, Nathaniel, IRAS OH Epidemiology Chemical Agents, IRAS – One Health Chemical, Berndt, Sonja I, Vijai, Joseph, Benavente, Yolanda, Camp, Nicola J, Nieters, Alexandra, Wang, Zhaoming, Smedby, Karin E, Kleinstern, Geffen, Hjalgrim, Henrik, Besson, Caroline, Skibola, Christine F, Morton, Lindsay M, Brooks-Wilson, Angela R, Teras, Lauren R, Breeze, Charles, Arias, Joshua, Adami, Hans-Olov, Albanes, Demetrius, Anderson, Kenneth C, Ansell, Stephen M, Bassig, Bryan, Becker, Nikolaus, Bhatti, Parveen, Birmann, Brenda M, Boffetta, Paolo, Bracci, Paige M, Brennan, Paul, Brown, Elizabeth E, Burdett, Laurie, Cannon-Albright, Lisa A, Chang, Ellen T, Chiu, Brian C H, Chung, Charles C, Clavel, Jacqueline, Cocco, Pierluigi, Colditz, Graham, Conde, Lucia, Conti, David V, Cox, David G, Curtin, Karen, Casabonne, Delphine, De Vivo, Immaculata, Diepstra, Arjan, Diver, W Ryan, Dogan, Ahmet, Edlund, Christopher K, Foretova, Lenka, Fraumeni, Joseph F, Gabbas, Attilio, Ghesquières, Hervé, Giles, Graham G, Glaser, Sally, Glenn, Martha, Glimelius, Bengt, Gu, Jian, Habermann, Thomas M, Haiman, Christopher A, Haioun, Corinne, Hofmann, Jonathan N, Holford, Theodore R, Holly, Elizabeth A, Hutchinson, Amy, Izhar, Aalin, Jackson, Rebecca D, Jarrett, Ruth F, Kaaks, Rudolph, Kane, Eleanor, Kolonel, Laurence N, Kong, Yinfei, Kraft, Peter, Kricker, Anne, Lake, Annette, Lan, Qing, Lawrence, Charles, Li, Dalin, Liebow, Mark, Link, Brian K, Magnani, Corrado, Maynadie, Marc, McKay, James, Melbye, Mads, Miligi, Lucia, Milne, Roger L, Molina, Thierry J, Monnereau, Alain, Montalvan, Rebecca, North, Kari E, Novak, Anne J, Onel, Kenan, Purdue, Mark P, Rand, Kristin A, Riboli, Elio, Riby, Jacques, Roman, Eve, Salles, Gilles, Sborov, Douglas W, Severson, Richard K, Shanafelt, Tait D, Smith, Martyn T, Smith, Alexandra, Song, Kevin W, Song, Lei, Southey, Melissa C, Spinelli, John J, Staines, Anthony, Stephens, Deborah, Sutherland, Heather J, Tkachuk, Kaitlyn, Thompson, Carrie A, Tilly, Hervé, Tinker, Lesley F, Travis, Ruth C, Turner, Jenny, Vachon, Celine M, Vajdic, Claire M, Van Den Berg, Anke, Van Den Berg, David J, Vermeulen, Roel C H, Vineis, Paolo, Wang, Sophia S, Weiderpass, Elisabete, Weiner, George J, Weinstein, Stephanie, Doo, Nicole Wong, Ye, Yuanqing, Yeager, Meredith, Yu, Kai, Zeleniuch-Jacquotte, Anne, Zhang, Yawei, Zheng, Tongzhang, Ziv, Elad, Sampson, Joshua, Chatterjee, Nilanjan, Offit, Kenneth, Cozen, Wendy, Wu, Xifeng, Cerhan, James R, Chanock, Stephen J, Slager, Susan L, and Rothman, Nathaniel

Published
2023

141. Ancestral diversity in lipoprotein(a) studies helps address evidence gaps

Author

Lee, Moa P., Dimos, Sofia F., Raffield, Laura M., Wang, Zhe, Ballou, Anna F., Downie, Carolina G., Arehart, Christopher H., Correa, Adolfo, De Vries, Paul S., Du, Zhaohui, Gignoux, Christopher R., Gordon-Larsen, Penny, Guo, Xiuqing, Haessler, Jeffrey, Howard, Annie Green, Hu, Yao, Kassahun, Helina, Kent, Shia T., Lopez, J. Antonio G., Monda, Keri L., North, Kari E., Peters, Ulrike, Preuss, Michael H., Rich, Stephen S., Rhodes, Shannon L., Yao, Jie, Yarosh, Rina, Tsai, Michael Y., Rotter, Jerome I., Kooperberg, Charles L., Loos, Ruth J.F., Ballantyne, Christie, Avery, Christy L., Graff, Mariaelisa, Lee, Moa P., Dimos, Sofia F., Raffield, Laura M., Wang, Zhe, Ballou, Anna F., Downie, Carolina G., Arehart, Christopher H., Correa, Adolfo, De Vries, Paul S., Du, Zhaohui, Gignoux, Christopher R., Gordon-Larsen, Penny, Guo, Xiuqing, Haessler, Jeffrey, Howard, Annie Green, Hu, Yao, Kassahun, Helina, Kent, Shia T., Lopez, J. Antonio G., Monda, Keri L., North, Kari E., Peters, Ulrike, Preuss, Michael H., Rich, Stephen S., Rhodes, Shannon L., Yao, Jie, Yarosh, Rina, Tsai, Michael Y., Rotter, Jerome I., Kooperberg, Charles L., Loos, Ruth J.F., Ballantyne, Christie, Avery, Christy L., and Graff, Mariaelisa

Abstract

Introduction The independent and causal cardiovascular disease risk factor lipoprotein(a) (Lp(a)) is elevated in >1.5 billion individuals worldwide, but studies have prioritised European populations. Methods Here, we examined how ancestrally diverse studies could clarify Lp(a)’s genetic architecture, inform efforts examining application of Lp(a) polygenic risk scores (PRS), enable causal inference and identify unexpected Lp(a) phenotypic effects using data from African (n=25 208), East Asian (n=2895), European (n=362 558), South Asian (n=8192) and Hispanic/Latino (n=8946) populations. Results Fourteen genome-wide significant loci with numerous population specific signals of large effect were identified that enabled construction of Lp(a) PRS of moderate (R2=15% in East Asians) to high (R2=50% in Europeans) accuracy. For all populations, PRS showed promise as a ‘rule out’ for elevated Lp(a) because certainty of assignment to the low-risk threshold was high (88.0%– 99.9%) across PRS thresholds (80th–99th percentile). Causal effects of increased Lp(a) with increased glycated haemoglobin were estimated for Europeans (p value =1.4×10−6), although inverse effects in Africans and East Asians suggested the potential for heterogeneous causal effects. Finally, Hispanic/Latinos were the only population in which known associations with coronary atherosclerosis and ischaemic heart disease were identified in external testing of Lp(a) PRS phenotypic effects. Conclusions Our results emphasise the merits of prioritising ancestral diversity when addressing Lp(a) evidence gaps., Introduction The independent and causal cardiovascular disease risk factor lipoprotein(a) (Lp(a)) is elevated in >1.5 billion individuals worldwide, but studies have prioritised European populations. Methods Here, we examined how ancestrally diverse studies could clarify Lp(a)'s genetic architecture, inform efforts examining application of Lp(a) polygenic risk scores (PRS), enable causal inference and identify unexpected Lp(a) phenotypic effects using data from African (n=25 208), East Asian (n=2895), European (n=362 558), South Asian (n=8192) and Hispanic/Latino (n=8946) populations. Results Fourteen genome-wide significant loci with numerous population specific signals of large effect were identified that enabled construction of Lp(a) PRS of moderate (R 2 =15% in East Asians) to high (R 2 =50% in Europeans) accuracy. For all populations, PRS showed promise as a 'rule out' for elevated Lp(a) because certainty of assignment to the low-risk threshold was high (88.0%-99.9%) across PRS thresholds (80th-99th percentile). Causal effects of increased Lp(a) with increased glycated haemoglobin were estimated for Europeans (p value =1.4×10 -6), although inverse effects in Africans and East Asians suggested the potential for heterogeneous causal effects. Finally, Hispanic/Latinos were the only population in which known associations with coronary atherosclerosis and ischaemic heart disease were identified in external testing of Lp(a) PRS phenotypic effects. Conclusions Our results emphasise the merits of prioritising ancestral diversity when addressing Lp(a) evidence gaps.

Published
2023

142. Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci

Author

de las Fuentes, Lisa, Schwander, Karen L., Brown, Michael R., Bentley, Amy R., Winkler, Thomas W., Sung, Yun Ju, Munroe, Patricia B., Miller, Clint L., Aschard, Hugo, Aslibekyan, Stella, Bartz, Traci M., Bielak, Lawrence F., Chai, Jin Fang, Cheng, Ching Yu, Dorajoo, Rajkumar, Feitosa, Mary F., Guo, Xiuqing, Hartwig, Fernando P., Horimoto, Andrea, Kolčić, Ivana, Lim, Elise, Liu, Yongmei, Manning, Alisa K., Marten, Jonathan, Musani, Solomon K., Noordam, Raymond, Padmanabhan, Sandosh, Rankinen, Tuomo, Richard, Melissa A., Ridker, Paul M., Smith, Albert V., Vojinovic, Dina, Zonderman, Alan B., Alver, Maris, Boissel, Mathilde, Christensen, Kaare, Freedman, Barry I., Gao, Chuan, Giulianini, Franco, Harris, Sarah E., He, Meian, Hsu, Fang Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo Pekka, Nolte, Ilja M., Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Sofer, Tamar, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Verweij, Niek, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhan, Yiqiang, Amin, Najaf, Arking, Dan E., Ballantyne, Christie, Boerwinkle, Eric, Brody, Jennifer A., Broeckel, Ulrich, Campbell, Archie, Canouil, Mickaël, Chai, Xiaoran, Chen, Yii Der Ida, Chen, Xu, Chitrala, Kumaraswamy Naidu, Concas, Maria Pina, de Faire, Ulf, de Mutsert, Renée, de Silva, H. Janaka, de Vries, Paul S., Do, Ahn, Faul, Jessica D., Fisher, Virginia, Floyd, James S., Forrester, Terrence, Friedlander, Yechiel, Girotto, Giorgia, Gu, C. Charles, Hallmans, Göran, Heikkinen, Sami, Heng, Chew Kiat, Homuth, Georg, Hunt, Steven, Ikram, M. Arfan, Jacobs, David R., Kavousi, Maryam, Khor, Chiea Chuen, Kilpeläinen, Tuomas O., Koh, Woon Puay, Komulainen, Pirjo, Langefeld, Carl D., Liang, Jingjing, Liu, Kiang, Liu, Jianjun, Lohman, Kurt, Mägi, Reedik, Manichaikul, Ani W., McKenzie, Colin A., Meitinger, Thomas, Milaneschi, Yuri, Nauck, Matthias, Nelson, Christopher P., O’Connell, Jeffrey R., Palmer, Nicholette D., Pereira, Alexandre C., Perls, Thomas, Peters, Annette, Polašek, Ozren, Raitakari, Olli T., Rice, Kenneth, Rice, Treva K., Rich, Stephen S., Sabanayagam, Charumathi, Schreiner, Pamela J., Shu, Xiao Ou, Sidney, Stephen, Sims, Mario, Smith, Jennifer A., Starr, John M., Strauch, Konstantin, Tai, E. Shyong, Taylor, Kent D., Tsai, Michael Y., Uitterlinden, André G., van Heemst, Diana, Waldenberger, Melanie, Wang, Ya Xing, Wei, Wen Bin, Wilson, Gregory, Xuan, Deng, Yao, Jie, Yu, Caizheng, Yuan, Jian Min, Zhao, Wei, Becker, Diane M., Bonnefond, Amélie, Bowden, Donald W., Cooper, Richard S., Deary, Ian J., Divers, Jasmin, Esko, Tõnu, Franks, Paul W., Froguel, Philippe, Gieger, Christian, Jonas, Jost B., Kato, Norihiro, Lakka, Timo A., Leander, Karin, Lehtimäki, Terho, Magnusson, Patrik K.E., North, Kari E., Ntalla, Ioanna, Penninx, Brenda, Samani, Nilesh J., Snieder, Harold, Spedicati, Beatrice, van der Harst, Pim, Völzke, Henry, Wagenknecht, Lynne E., Weir, David R., Wojczynski, Mary K., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Bouchard, Claude, Chasman, Daniel I., Evans, Michele K., Fox, Ervin R., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kardia, Sharon L.R., Krieger, Jose Eduardo, Mook-Kanamori, Dennis O., Peyser, Patricia A., Province, Michael M., Psaty, Bruce M., Rudan, Igor, Sim, Xueling, Smith, Blair H., van Dam, Rob M., van Duijn, Cornelia M., Wong, Tien Yin, Arnett, Donna K., Rao, Dabeeru C., Gauderman, James, Liu, Ching Ti, Morrison, Alanna C., Rotter, Jerome I., Fornage, Myriam, de las Fuentes, Lisa, Schwander, Karen L., Brown, Michael R., Bentley, Amy R., Winkler, Thomas W., Sung, Yun Ju, Munroe, Patricia B., Miller, Clint L., Aschard, Hugo, Aslibekyan, Stella, Bartz, Traci M., Bielak, Lawrence F., Chai, Jin Fang, Cheng, Ching Yu, Dorajoo, Rajkumar, Feitosa, Mary F., Guo, Xiuqing, Hartwig, Fernando P., Horimoto, Andrea, Kolčić, Ivana, Lim, Elise, Liu, Yongmei, Manning, Alisa K., Marten, Jonathan, Musani, Solomon K., Noordam, Raymond, Padmanabhan, Sandosh, Rankinen, Tuomo, Richard, Melissa A., Ridker, Paul M., Smith, Albert V., Vojinovic, Dina, Zonderman, Alan B., Alver, Maris, Boissel, Mathilde, Christensen, Kaare, Freedman, Barry I., Gao, Chuan, Giulianini, Franco, Harris, Sarah E., He, Meian, Hsu, Fang Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo Pekka, Nolte, Ilja M., Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Sofer, Tamar, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Verweij, Niek, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhan, Yiqiang, Amin, Najaf, Arking, Dan E., Ballantyne, Christie, Boerwinkle, Eric, Brody, Jennifer A., Broeckel, Ulrich, Campbell, Archie, Canouil, Mickaël, Chai, Xiaoran, Chen, Yii Der Ida, Chen, Xu, Chitrala, Kumaraswamy Naidu, Concas, Maria Pina, de Faire, Ulf, de Mutsert, Renée, de Silva, H. Janaka, de Vries, Paul S., Do, Ahn, Faul, Jessica D., Fisher, Virginia, Floyd, James S., Forrester, Terrence, Friedlander, Yechiel, Girotto, Giorgia, Gu, C. Charles, Hallmans, Göran, Heikkinen, Sami, Heng, Chew Kiat, Homuth, Georg, Hunt, Steven, Ikram, M. Arfan, Jacobs, David R., Kavousi, Maryam, Khor, Chiea Chuen, Kilpeläinen, Tuomas O., Koh, Woon Puay, Komulainen, Pirjo, Langefeld, Carl D., Liang, Jingjing, Liu, Kiang, Liu, Jianjun, Lohman, Kurt, Mägi, Reedik, Manichaikul, Ani W., McKenzie, Colin A., Meitinger, Thomas, Milaneschi, Yuri, Nauck, Matthias, Nelson, Christopher P., O’Connell, Jeffrey R., Palmer, Nicholette D., Pereira, Alexandre C., Perls, Thomas, Peters, Annette, Polašek, Ozren, Raitakari, Olli T., Rice, Kenneth, Rice, Treva K., Rich, Stephen S., Sabanayagam, Charumathi, Schreiner, Pamela J., Shu, Xiao Ou, Sidney, Stephen, Sims, Mario, Smith, Jennifer A., Starr, John M., Strauch, Konstantin, Tai, E. Shyong, Taylor, Kent D., Tsai, Michael Y., Uitterlinden, André G., van Heemst, Diana, Waldenberger, Melanie, Wang, Ya Xing, Wei, Wen Bin, Wilson, Gregory, Xuan, Deng, Yao, Jie, Yu, Caizheng, Yuan, Jian Min, Zhao, Wei, Becker, Diane M., Bonnefond, Amélie, Bowden, Donald W., Cooper, Richard S., Deary, Ian J., Divers, Jasmin, Esko, Tõnu, Franks, Paul W., Froguel, Philippe, Gieger, Christian, Jonas, Jost B., Kato, Norihiro, Lakka, Timo A., Leander, Karin, Lehtimäki, Terho, Magnusson, Patrik K.E., North, Kari E., Ntalla, Ioanna, Penninx, Brenda, Samani, Nilesh J., Snieder, Harold, Spedicati, Beatrice, van der Harst, Pim, Völzke, Henry, Wagenknecht, Lynne E., Weir, David R., Wojczynski, Mary K., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Bouchard, Claude, Chasman, Daniel I., Evans, Michele K., Fox, Ervin R., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kardia, Sharon L.R., Krieger, Jose Eduardo, Mook-Kanamori, Dennis O., Peyser, Patricia A., Province, Michael M., Psaty, Bruce M., Rudan, Igor, Sim, Xueling, Smith, Blair H., van Dam, Rob M., van Duijn, Cornelia M., Wong, Tien Yin, Arnett, Donna K., Rao, Dabeeru C., Gauderman, James, Liu, Ching Ti, Morrison, Alanna C., Rotter, Jerome I., and Fornage, Myriam

Abstract

Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. Methods:A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: “Some College” (yes/no, for any education beyond high school) and “Graduated College” (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10−8) and suggestive (p < 1 × 10−6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals). Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue.Discussion: Genome-wide interaction analysis of educational a

Published
2023

143. Whole-exome sequence analysis of anthropometric traits illustrates challenges in identifying effects of rare genetic variants

Author

Young, Kristin L., Fisher, Virginia, Deng, Xuan, Brody, Jennifer A., Graff, Misa, Lim, Elise, Lin, Bridget M., Xu, Hanfei, Amin, Najaf, An, Ping, Aslibekyan, Stella, Fohner, Alison E., Hidalgo, Bertha, Lenzini, Petra, Kraaij, Robert, Medina-Gomez, Carolina, Prokić, Ivana, Rivadeneira, Fernando, Sitlani, Colleen, Tao, Ran, van Rooij, Jeroen, Zhang, Di, Broome, Jai G., Buth, Erin J., Heavner, Benjamin D., Jain, Deepti, Smith, Albert V., Barnes, Kathleen, Boorgula, Meher Preethi, Chavan, Sameer, Darbar, Dawood, De Andrade, Mariza, Guo, Xiuqing, Haessler, Jeffrey, Irvin, Marguerite R., Kalyani, Rita R., Kardia, Sharon L.R., Kooperberg, Charles, Kim, Wonji, Mathias, Rasika A., McDonald, Merry Lynn, Mitchell, Braxton D., Peyser, Patricia A., Regan, Elizabeth A., Redline, Susan, Reiner, Alexander P., Rich, Stephen S., Rotter, Jerome I., Smith, Jennifer A., Weiss, Scott, Wiggins, Kerri L., Yanek, Lisa R., Arnett, Donna, Heard-Costa, Nancy L., Leal, Suzanne, Lin, Danyu, McKnight, Barbara, Province, Michael, van Duijn, Cornelia M., North, Kari E., Cupples, L. Adrienne, Liu, Ching Ti, Young, Kristin L., Fisher, Virginia, Deng, Xuan, Brody, Jennifer A., Graff, Misa, Lim, Elise, Lin, Bridget M., Xu, Hanfei, Amin, Najaf, An, Ping, Aslibekyan, Stella, Fohner, Alison E., Hidalgo, Bertha, Lenzini, Petra, Kraaij, Robert, Medina-Gomez, Carolina, Prokić, Ivana, Rivadeneira, Fernando, Sitlani, Colleen, Tao, Ran, van Rooij, Jeroen, Zhang, Di, Broome, Jai G., Buth, Erin J., Heavner, Benjamin D., Jain, Deepti, Smith, Albert V., Barnes, Kathleen, Boorgula, Meher Preethi, Chavan, Sameer, Darbar, Dawood, De Andrade, Mariza, Guo, Xiuqing, Haessler, Jeffrey, Irvin, Marguerite R., Kalyani, Rita R., Kardia, Sharon L.R., Kooperberg, Charles, Kim, Wonji, Mathias, Rasika A., McDonald, Merry Lynn, Mitchell, Braxton D., Peyser, Patricia A., Regan, Elizabeth A., Redline, Susan, Reiner, Alexander P., Rich, Stephen S., Rotter, Jerome I., Smith, Jennifer A., Weiss, Scott, Wiggins, Kerri L., Yanek, Lisa R., Arnett, Donna, Heard-Costa, Nancy L., Leal, Suzanne, Lin, Danyu, McKnight, Barbara, Province, Michael, van Duijn, Cornelia M., North, Kari E., Cupples, L. Adrienne, and Liu, Ching Ti

Abstract

Anthropometric traits, measuring body size and shape, are highly heritable and significant clinical risk factors for cardiometabolic disorders. These traits have been extensively studied in genome-wide association studies (GWASs), with hundreds of genome-wide significant loci identified. We performed a whole-exome sequence analysis of the genetics of height, body mass index (BMI) and waist/hip ratio (WHR). We meta-analyzed single-variant and gene-based associations of whole-exome sequence variation with height, BMI, and WHR in up to 22,004 individuals, and we assessed replication of our findings in up to 16,418 individuals from 10 independent cohorts from Trans-Omics for Precision Medicine (TOPMed). We identified four trait associations with single-nucleotide variants (SNVs; two for height and two for BMI) and replicated the LECT2 gene association with height. Our expression quantitative trait locus (eQTL) analysis within previously reported GWAS loci implicated CEP63 and RFT1 as potential functional genes for known height loci. We further assessed enrichment of SNVs, which were monogenic or syndromic variants within loci associated with our three traits. This led to the significant enrichment results for height, whereas we observed no Bonferroni-corrected significance for all SNVs. With a sample size of ∼20,000 whole-exome sequences in our discovery dataset, our findings demonstrate the importance of genomic sequencing in genetic association studies, yet they also illustrate the challenges in identifying effects of rare genetic variants.

Published
2023

144. Multi-ancestry genome-wide gene–sleep interactions identify novel loci for blood pressure

Author

Wang, Heming, Noordam, Raymond, Cade, Brian E., Schwander, Karen, Winkler, Thomas W., Lee, Jiwon, Sung, Yun Ju, Bentley, Amy R., Manning, Alisa K., Aschard, Hugues, Kilpeläinen, Tuomas O., Ilkov, Marjan, Brown, Michael R., Horimoto, Andrea R., Richard, Melissa, Bartz, Traci M., Vojinovic, Dina, Lim, Elise, Nierenberg, Jovia L., Liu, Yongmei, Chitrala, Kumaraswamynaidu, Rankinen, Tuomo, Musani, Solomon K., Franceschini, Nora, Rauramaa, Rainer, Alver, Maris, Zee, Phyllis C., Harris, Sarah E., van der Most, Peter J., Nolte, Ilja M., Munroe, Patricia B., Palmer, Nicholette D., Kühnel, Brigitte, Weiss, Stefan, Wen, Wanqing, Hall, Kelly A., Lyytikäinen, Leo-Pekka, O’Connell, Jeff, Eiriksdottir, Gudny, Launer, Lenore J., de Vries, Paul S., Arking, Dan E., Chen, Han, Boerwinkle, Eric, Krieger, Jose E., Schreiner, Pamela J., Sidney, Stephen, Shikany, James M., Rice, Kenneth, Chen, Yii-Der Ida, Gharib, Sina A., Bis, Joshua C., Luik, Annemarie I., Ikram, M. Arfan, Uitterlinden, André G., Amin, Najaf, Xu, Hanfei, Levy, Daniel, He, Jiang, Lohman, Kurt K., Zonderman, Alan B., Rice, Treva K., Sims, Mario, Wilson, Gregory, Sofer, Tamar, Rich, Stephen S., Palmas, Walter, Yao, Jie, Guo, Xiuqing, Rotter, Jerome I., Biermasz, Nienke R., Mook-Kanamori, Dennis O., Martin, Lisa W., Barac, Ana, Wallace, Robert B., Gottlieb, Daniel J., Komulainen, Pirjo, Heikkinen, Sami, Mägi, Reedik, Milani, Lili, Metspalu, Andres, Starr, John M., Milaneschi, Yuri, Waken, R. J., Gao, Chuan, Waldenberger, Melanie, Peters, Annette, Strauch, Konstantin, Meitinger, Thomas, Roenneberg, Till, Völker, Uwe, Dörr, Marcus, Shu, Xiao-Ou, Mukherjee, Sutapa, Hillman, David R., Kähönen, Mika, Wagenknecht, Lynne E., Gieger, Christian, Grabe, Hans J., Zheng, Wei, Palmer, Lyle J., Lehtimäki, Terho, Gudnason, Vilmundur, Morrison, Alanna C., Pereira, Alexandre C., Fornage, Myriam, Psaty, Bruce M., van Duijn, Cornelia M., Liu, Ching-Ti, Kelly, Tanika N., Evans, Michele K., Bouchard, Claude, Fox, Ervin R., Kooperberg, Charles, Zhu, Xiaofeng, Lakka, Timo A., Esko, Tõnu, North, Kari E., Deary, Ian J., Snieder, Harold, Penninx, Brenda W. J. H., Gauderman, W. James, Rao, Dabeeru C., Redline, Susan, and van Heemst, Diana

Abstract

Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups in two stages using 2 degree of freedom (df) joint test followed by 1df test of interaction effects. Primary multi-ancestry analysis in 62,969 individuals in stage 1 identified three novel gene by sleep interactions that were replicated in an additional 59,296 individuals in stage 2 (stage 1 + 2 Pjoint< 5 × 10−8), including rs7955964 (FIGNL2/ANKRD33) that increases BP among long sleepers, and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) that increase BP among short sleepers (Pint< 5 × 10−8). Secondary ancestry-specific analysis identified another novel gene by long sleep interaction at rs111887471 (TRPC3/KIAA1109) in individuals of African ancestry (Pint= 2 × 10−6). Combined stage 1 and 2 analyses additionally identified significant gene by long sleep interactions at 10 loci including MKLN1and RGL3/ELAVL3previously associated with BP, and significant gene by short sleep interactions at 10 loci including C2orf43 previously associated with BP (Pint< 10−3). 2df test also identified novel loci for BP after modeling sleep that has known functions in sleep–wake regulation, nervous and cardiometabolic systems. This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.

Published
2024
Full Text
View/download PDF

145. Fine mapping and identification of serum urate loci in American Indians: The Strong Heart Family Study

Author

Chittoor, Geetha, Haack, Karin, Balakrishnan, Poojitha, Bizon, Christopher, Laston, Sandra, Best, Lyle G., MacCluer, Jean W., North, Kari E., Umans, Jason G., Franceschini, Nora, Prasad, Gauri, Macias-Kauffer, Luis, Villarreal-Molina, Teresa, Bharadwaj, Dwaipayan, Canizales-Quinteros, Samuel, Navas-Acien, Ana, Cole, Shelley A., and Voruganti, V. S.

Published
2019
Full Text
View/download PDF

146. Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration

Author

Noordam, Raymond, Bos, Maxime M., Wang, Heming, Winkler, Thomas W., Bentley, Amy R., Kilpeläinen, Tuomas O., de Vries, Paul S., Sung, Yun Ju, Schwander, Karen, Cade, Brian E., Manning, Alisa, Aschard, Hugues, Brown, Michael R., Chen, Han, Franceschini, Nora, Musani, Solomon K., Richard, Melissa, Vojinovic, Dina, Aslibekyan, Stella, Bartz, Traci M., de las Fuentes, Lisa, Feitosa, Mary, Horimoto, Andrea R., Ilkov, Marjan, Kho, Minjung, Kraja, Aldi, Li, Changwei, Lim, Elise, Liu, Yongmei, Mook-Kanamori, Dennis O., Rankinen, Tuomo, Tajuddin, Salman M., van der Spek, Ashley, Wang, Zhe, Marten, Jonathan, Laville, Vincent, Alver, Maris, Evangelou, Evangelos, Graff, Maria E., He, Meian, Kühnel, Brigitte, Lyytikäinen, Leo-Pekka, Marques-Vidal, Pedro, Nolte, Ilja M., Palmer, Nicholette D., Rauramaa, Rainer, Shu, Xiao-Ou, Snieder, Harold, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Adolfo, Correa, Ballantyne, Christie, Bielak, Larry, Biermasz, Nienke R., Boerwinkle, Eric, Dimou, Niki, Eiriksdottir, Gudny, Gao, Chuan, Gharib, Sina A., Gottlieb, Daniel J., Haba-Rubio, José, Harris, Tamara B., Heikkinen, Sami, Heinzer, Raphaël, Hixson, James E., Homuth, Georg, Ikram, M. Arfan, Komulainen, Pirjo, Krieger, Jose E., Lee, Jiwon, Liu, Jingmin, Lohman, Kurt K., Luik, Annemarie I., Mägi, Reedik, Martin, Lisa W., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Nalls, Mike A., O’Connell, Jeff, Peters, Annette, Peyser, Patricia, Raitakari, Olli T., Reiner, Alex P., Rensen, Patrick C. N., Rice, Treva K., Rich, Stephen S., Roenneberg, Till, Rotter, Jerome I., Schreiner, Pamela J., Shikany, James, Sidney, Stephen S., Sims, Mario, Sitlani, Colleen M., Sofer, Tamar, Strauch, Konstantin, Swertz, Morris A., Taylor, Kent D., Uitterlinden, André G., van Duijn, Cornelia M., Völzke, Henry, Waldenberger, Melanie, Wallance, Robert B., van Dijk, Ko Willems, Yu, Caizheng, Zonderman, Alan B., Becker, Diane M., Elliott, Paul, Esko, Tõnu, Gieger, Christian, Grabe, Hans J., Lakka, Timo A., Lehtimäki, Terho, North, Kari E., Penninx, Brenda W. J. H., Vollenweider, Peter, Wagenknecht, Lynne E., Wu, Tangchun, Xiang, Yong-Bing, Zheng, Wei, Arnett, Donna K., Bouchard, Claude, Evans, Michele K., Gudnason, Vilmundur, Kardia, Sharon, Kelly, Tanika N., Kritchevsky, Stephen B., Loos, Ruth J. F., Pereira, Alexandre C., Province, Mike, Psaty, Bruce M., Rotimi, Charles, Zhu, Xiaofeng, Amin, Najaf, Cupples, L. Adrienne, Fornage, Myriam, Fox, Ervin F., Guo, Xiuqing, Gauderman, W. James, Rice, Kenneth, Kooperberg, Charles, Munroe, Patricia B., Liu, Ching-Ti, Morrison, Alanna C., Rao, Dabeeru C., van Heemst, Diana, and Redline, Susan

Published
2019
Full Text
View/download PDF

147. Associations of autozygosity with a broad range of human phenotypes

Author

Clark, David W, Okada, Yukinori, Moore, Kristjan H S, Mason, Dan, Pirastu, Nicola, Gandin, Ilaria, Mattsson, Hannele, Barnes, Catriona L K, Lin, Kuang, Zhao, Jing Hua, Deelen, Patrick, Rohde, Rebecca, Schurmann, Claudia, Guo, Xiuqing, Giulianini, Franco, Zhang, Weihua, Medina-Gomez, Carolina, Karlsson, Robert, Bao, Yanchun, Bartz, Traci M, Baumbach, Clemens, Biino, Ginevra, Bixley, Matthew J, Brumat, Marco, Chai, Jin-Fang, Corre, Tanguy, Cousminer, Diana L, Dekker, Annelot M, Eccles, David A, van Eijk, Kristel R, Fuchsberger, Christian, Gao, He, Germain, Marine, Gordon, Scott D, de Haan, Hugoline G, Harris, Sarah E, Hofer, Edith, Huerta-Chagoya, Alicia, Igartua, Catherine, Jansen, Iris E, Jia, Yucheng, Kacprowski, Tim, Karlsson, Torgny, Kleber, Marcus E, Li, Shengchao Alfred, Li-Gao, Ruifang, Mahajan, Anubha, Matsuda, Koichi, Meidtner, Karina, Meng, Weihua, Montasser, May E, van der Most, Peter J, Munz, Matthias, Nutile, Teresa, Palviainen, Teemu, Prasad, Gauri, Prasad, Rashmi B, Priyanka, Tallapragada Divya Sri, Rizzi, Federica, Salvi, Erika, Sapkota, Bishwa R, Shriner, Daniel, Skotte, Line, Smart, Melissa C, Smith, Albert Vernon, van der Spek, Ashley, Spracklen, Cassandra N, Strawbridge, Rona J, Tajuddin, Salman M, Trompet, Stella, Turman, Constance, Verweij, Niek, Viberti, Clara, Wang, Lihua, Warren, Helen R, Wootton, Robyn E, Yanek, Lisa R, Yao, Jie, Yousri, Noha A, Zhao, Wei, Adeyemo, Adebowale A, Afaq, Saima, Aguilar-Salinas, Carlos Alberto, Akiyama, Masato, Albert, Matthew L, Allison, Matthew A, Alver, Maris, Aung, Tin, Azizi, Fereidoun, Bentley, Amy R, Boeing, Heiner, Boerwinkle, Eric, Borja, Judith B, de Borst, Gert J, Bottinger, Erwin P, Broer, Linda, Campbell, Harry, Chanock, Stephen, Chee, Miao-Li, Chen, Guanjie, Chen, Yii-Der I, Chen, Zhengming, Chiu, Yen-Feng, Cocca, Massimiliano, Collins, Francis S, Concas, Maria Pina, Corley, Janie, Cugliari, Giovanni, van Dam, Rob M, Damulina, Anna, Daneshpour, Maryam S, Day, Felix R, Delgado, Graciela E, Dhana, Klodian, Doney, Alexander S F, Dörr, Marcus, Doumatey, Ayo P, Dzimiri, Nduna, Ebenesersdóttir, S Sunna, Elliott, Joshua, Elliott, Paul, Ewert, Ralf, Felix, Janine F, Fischer, Krista, Freedman, Barry I, Girotto, Giorgia, Goel, Anuj, Gögele, Martin, Goodarzi, Mark O, Graff, Mariaelisa, Granot-Hershkovitz, Einat, Grodstein, Francine, Guarrera, Simonetta, Gudbjartsson, Daniel F, Guity, Kamran, Gunnarsson, Bjarni, Guo, Yu, Hagenaars, Saskia P, Haiman, Christopher A, Halevy, Avner, Harris, Tamara B, Hedayati, Mehdi, van Heel, David A, Hirata, Makoto, Höfer, Imo, Hsiung, Chao Agnes, Huang, Jinyan, Hung, Yi-Jen, Ikram, M Arfan, Jagadeesan, Anuradha, Jousilahti, Pekka, Kamatani, Yoichiro, Kanai, Masahiro, Kerrison, Nicola D, Kessler, Thorsten, Khaw, Kay-Tee, Khor, Chiea Chuen, de Kleijn, Dominique P V, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter, Krämer, Bernhard K, Kutalik, Zoltán, Kuusisto, Johanna, Langenberg, Claudia, Launer, Lenore J, Lawlor, Deborah A, Lee, I-Te, Lee, Wen-Jane, Lerch, Markus M, Li, Liming, Liu, Jianjun, Loh, Marie, London, Stephanie J, Loomis, Stephanie, Lu, Yingchang, Luan, Jian’an, Mägi, Reedik, Manichaikul, Ani W, Manunta, Paolo, Másson, Gísli, Matoba, Nana, Mei, Xue W, Meisinger, Christa, Meitinger, Thomas, Mezzavilla, Massimo, Milani, Lili, Millwood, Iona Y, Momozawa, Yukihide, Moore, Amy, Morange, Pierre-Emmanuel, Moreno-Macías, Hortensia, Mori, Trevor A, Morrison, Alanna C, Muka, Taulant, Murakami, Yoshinori, Murray, Alison D, de Mutsert, Renée, Mychaleckyj, Josyf C, Nalls, Mike A, Nauck, Matthias, Neville, Matt J, Nolte, Ilja M, Ong, Ken K, Orozco, Lorena, Padmanabhan, Sandosh, Pálsson, Gunnar, Pankow, James S, Pattaro, Cristian, Pattie, Alison, Polasek, Ozren, Poulter, Neil, Pramstaller, Peter P, Quintana-Murci, Lluis, Räikkönen, Katri, Ralhan, Sarju, Rao, Dabeeru C, van Rheenen, Wouter, Rich, Stephen S, Ridker, Paul M, Rietveld, Cornelius A, Robino, Antonietta, van Rooij, Frank J A, Ruggiero, Daniela, Saba, Yasaman, Sabanayagam, Charumathi, Sabater-Lleal, Maria, Sala, Cinzia Felicita, Salomaa, Veikko, Sandow, Kevin, Schmidt, Helena, Scott, Laura J, Scott, William R, Sedaghati-Khayat, Bahareh, Sennblad, Bengt, van Setten, Jessica, Sever, Peter J, Sheu, Wayne H-H, Shi, Yuan, Shrestha, Smeeta, Shukla, Sharvari Rahul, Sigurdsson, Jon K, Sikka, Timo Tonis, Singh, Jai Rup, Smith, Blair H, Stančáková, Alena, Stanton, Alice, Starr, John M, Stefansdottir, Lilja, Straker, Leon, Sulem, Patrick, Sveinbjornsson, Gardar, Swertz, Morris A, Taylor, Adele M, Taylor, Kent D, Terzikhan, Natalie, Tham, Yih-Chung, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tillander, Annika, Tracy, Russell P, Tusié-Luna, Teresa, Tzoulaki, Ioanna, Vaccargiu, Simona, Vangipurapu, Jagadish, Veldink, Jan H, Vitart, Veronique, Völker, Uwe, Vuoksimaa, Eero, Wakil, Salma M, Waldenberger, Melanie, Wander, Gurpreet S, Wang, Ya Xing, Wareham, Nicholas J, Wild, Sarah, Yajnik, Chittaranjan S, Yuan, Jian-Min, Zeng, Lingyao, Zhang, Liang, Zhou, Jie, Amin, Najaf, Asselbergs, Folkert W, Bakker, Stephan J L, Becker, Diane M, Lehne, Benjamin, Bennett, David A, van den Berg, Leonard H, Berndt, Sonja I, Bharadwaj, Dwaipayan, Bielak, Lawrence F, Bochud, Murielle, Boehnke, Mike, Bouchard, Claude, Bradfield, Jonathan P, Brody, Jennifer A, Campbell, Archie, Carmi, Shai, Caulfield, Mark J, Cesarini, David, Chambers, John C, Chandak, Giriraj Ratan, Cheng, Ching-Yu, Ciullo, Marina, Cornelis, Marilyn, Cusi, Daniele, Smith, George Davey, Deary, Ian J, Dorajoo, Rajkumar, van Duijn, Cornelia M, Ellinghaus, David, Erdmann, Jeanette, Eriksson, Johan G, Evangelou, Evangelos, Evans, Michele K, Faul, Jessica D, Feenstra, Bjarke, Feitosa, Mary, Foisy, Sylvain, Franke, Andre, Friedlander, Yechiel, Gasparini, Paolo, Gieger, Christian, Gonzalez, Clicerio, Goyette, Philippe, Grant, Struan F A, Griffiths, Lyn R, Groop, Leif, Gudnason, Vilmundur, Gyllensten, Ulf, Hakonarson, Hakon, Hamsten, Anders, van der Harst, Pim, Heng, Chew-Kiat, Hicks, Andrew A, Hochner, Hagit, Huikuri, Heikki, Hunt, Steven C, Jaddoe, Vincent W V, De Jager, Philip L, Johannesson, Magnus, Johansson, Åsa, Jonas, Jost B, Jukema, J Wouter, Junttila, Juhani, Kaprio, Jaakko, Kardia, Sharon L. R., Karpe, Fredrik, Kumari, Meena, Laakso, Markku, van der Laan, Sander W, Lahti, Jari, Laudes, Matthias, Lea, Rodney A, Lieb, Wolfgang, Lumley, Thomas, Martin, Nicholas G, März, Winfried, Matullo, Giuseppe, McCarthy, Mark I, Medland, Sarah E, Merriman, Tony R, Metspalu, Andres, Meyer, Brian F, Mohlke, Karen L, Montgomery, Grant W, Mook-Kanamori, Dennis, Munroe, Patricia B, North, Kari E, Nyholt, Dale R, O’connell, Jeffery R, Ober, Carole, Oldehinkel, Albertine J, Palmas, Walter, Palmer, Colin, Pasterkamp, Gerard G, Patin, Etienne, Pennell, Craig E, Perusse, Louis, Peyser, Patricia A, Pirastu, Mario, Polderman, Tinca J. C., Porteous, David J, Posthuma, Danielle, Psaty, Bruce M, Rioux, John D, Rivadeneira, Fernando, Rotimi, Charles, Rotter, Jerome I, Rudan, Igor, Den Ruijter, Hester M, Sanghera, Dharambir K, Sattar, Naveed, Schmidt, Reinhold, Schulze, Matthias B, Schunkert, Heribert, Scott, Robert A, Shuldiner, Alan R, Sim, Xueling, Small, Neil, Smith, Jennifer A, Sotoodehnia, Nona, Tai, E-Shyong, Teumer, Alexander, Timpson, Nicholas J, Toniolo, Daniela, Tregouet, David-Alexandre, Tuomi, Tiinamaija, Vollenweider, Peter, Wang, Carol A, Weir, David R, Whitfield, John B, Wijmenga, Cisca, Wong, Tien-Yin, Wright, John, Yang, Jingyun, Yu, Lei, Zemel, Babette S, Zonderman, Alan B, Perola, Markus, Magnusson, Patrik K. E., Uitterlinden, André G, Kooner, Jaspal S, Chasman, Daniel I, Loos, Ruth J. F., Franceschini, Nora, Franke, Lude, Haley, Chris S, Hayward, Caroline, Walters, Robin G, Perry, John R. B., Esko, Tōnu, Helgason, Agnar, Stefansson, Kari, Joshi, Peter K, Kubo, Michiaki, and Wilson, James F

Published
2019
Full Text
View/download PDF

148. Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data

Author

Shungin, Dmitry, Haworth, Simon, Divaris, Kimon, Agler, Cary S., Kamatani, Yoichiro, Keun Lee, Myoung, Grinde, Kelsey, Hindy, George, Alaraudanjoki, Viivi, Pesonen, Paula, Teumer, Alexander, Holtfreter, Birte, Sakaue, Saori, Hirata, Jun, Yu, Yau-Hua, Ridker, Paul M., Giulianini, Franco, Chasman, Daniel I., Magnusson, Patrik K. E., Sudo, Takeaki, Okada, Yukinori, Völker, Uwe, Kocher, Thomas, Anttonen, Vuokko, Laitala, Marja-Liisa, Orho-Melander, Marju, Sofer, Tamar, Shaffer, John R., Vieira, Alexandre, Marazita, Mary L., Kubo, Michiaki, Furuichi, Yasushi, North, Kari E., Offenbacher, Steve, Ingelsson, Erik, Franks, Paul W., Timpson, Nicholas J., and Johansson, Ingegerd

Published
2019
Full Text
View/download PDF

149. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Author

Kilpeläinen, Tuomas O., Bentley, Amy R., Noordam, Raymond, Sung, Yun Ju, Schwander, Karen, Winkler, Thomas W., Jakupović, Hermina, Chasman, Daniel I., Manning, Alisa, Ntalla, Ioanna, Aschard, Hugues, Brown, Michael R., de las Fuentes, Lisa, Franceschini, Nora, Guo, Xiuqing, Vojinovic, Dina, Aslibekyan, Stella, Feitosa, Mary F., Kho, Minjung, Musani, Solomon K., Richard, Melissa, Wang, Heming, Wang, Zhe, Bartz, Traci M., Bielak, Lawrence F., Campbell, Archie, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Li, Changwei, Lohman, Kurt K., Marten, Jonathan, Sim, Xueling, Smith, Albert V., Tajuddin, Salman M., Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Graff, Mariaelisa, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Zhao, Jing Hua, Kraja, Aldi T., Kühnel, Brigitte, Laguzzi, Federica, Lyytikäinen, Leo-Pekka, Nolte, Ilja M., Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Rueedi, Rico, Stringham, Heather M., Takeuchi, Fumihiko, van der Most, Peter J., Varga, Tibor V., Verweij, Niek, Ware, Erin B., Wen, Wanqing, Li, Xiaoyin, Yanek, Lisa R., Amin, Najaf, Arnett, Donna K., Boerwinkle, Eric, Brumat, Marco, Cade, Brian, Canouil, Mickaël, Chen, Yii-Der Ida, Concas, Maria Pina, Connell, John, de Mutsert, Renée, de Silva, H. Janaka, de Vries, Paul S., Demirkan, Ayşe, Ding, Jingzhong, Eaton, Charles B., Faul, Jessica D., Friedlander, Yechiel, Gabriel, Kelley P., Ghanbari, Mohsen, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven C., Ikram, M. Arfan, Jonas, Jost B., Koh, Woon-Puay, Komulainen, Pirjo, Krieger, Jose E., Kritchevsky, Stephen B., Kutalik, Zoltán, Kuusisto, Johanna, Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Leander, Karin, Lemaitre, Rozenn N., Lewis, Cora E., Liang, Jingjing, Lifelines Cohort Study, Liu, Jianjun, Mägi, Reedik, Manichaikul, Ani, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Mohlke, Karen L., Mosley, Jr., Thomas H., Murray, Alison D., Nalls, Mike A., Nang, Ei-Ei Khaing, Nelson, Christopher P., Nona, Sotoodehnia, Norris, Jill M., Nwuba, Chiamaka Vivian, O’Connell, Jeff, Palmer, Nicholette D., Papanicolau, George J., Pazoki, Raha, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Porteous, David J., Poveda, Alaitz, Raitakari, Olli T., Rich, Stephen S., Risch, Neil, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Schreiner, Pamela J., Scott, Robert A., Sidney, Stephen S., Sims, Mario, Smith, Jennifer A., Snieder, Harold, Sofer, Tamar, Starr, John M., Sternfeld, Barbara, Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Tsai, Michael Y., Tuomilehto, Jaakko, Uitterlinden, André G., van der Ende, M. Yldau, van Heemst, Diana, Voortman, Trudy, Waldenberger, Melanie, Wennberg, Patrik, Wilson, Gregory, Xiang, Yong-Bing, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., de Faire, Ulf, Deary, Ian J., Elliott, Paul, Esko, Tõnu, Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Kato, Norihiro, Laakso, Markku, Lakka, Timo A., Lehtimäki, Terho, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Samani, Nilesh J., Shu, Xiao-Ou, van der Harst, Pim, Van Vliet-Ostaptchouk, Jana V., Vollenweider, Peter, Wagenknecht, Lynne E., Wang, Ya X., Wareham, Nicholas J., Weir, David R., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Evans, Michele K., Franks, Paul W., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kelly, Tanika N., Liu, Yongmei, North, Kari E., Pereira, Alexandre C., Ridker, Paul M., Tai, E. Shyong, van Dam, Rob M., Fox, Ervin R., Kardia, Sharon L. R., Liu, Ching-Ti, Mook-Kanamori, Dennis O., Province, Michael A., Redline, Susan, van Duijn, Cornelia M., Rotter, Jerome I., Kooperberg, Charles B., Gauderman, W. James, Psaty, Bruce M., Rice, Kenneth, Munroe, Patricia B., Fornage, Myriam, Cupples, L. Adrienne, Rotimi, Charles N., Morrison, Alanna C., Rao, Dabeeru C., and Loos, Ruth J. F.

Published
2019
Full Text
View/download PDF

150. Supplemental Tables 1 - 7 from Association of Cancer Susceptibility Variants with Risk of Multiple Primary Cancers: The Population Architecture using Genomics and Epidemiology Study

Author

Park, S. Lani, primary, Caberto, Christian P., primary, Lin, Yi, primary, Goodloe, Robert J., primary, Dumitrescu, Logan, primary, Love, Shelly-Ann, primary, Matise, Tara C., primary, Hindorff, Lucia A., primary, Fowke, Jay H., primary, Schumacher, Fredrick R., primary, Beebe-Dimmer, Jennifer, primary, Chen, Chu, primary, Hou, Lifang, primary, Thomas, Fridtjof, primary, Deelman, Ewa, primary, Han, Ying, primary, Peters, Ulrike, primary, North, Kari E., primary, Heiss, Gerardo, primary, Crawford, Dana C., primary, Haiman, Christopher A., primary, Wilkens, Lynne R., primary, Bush, William S., primary, Kooperberg, Charles, primary, Cheng, Iona, primary, and Le Marchand, Loïc, primary

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results