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1. Genetic pleiotropy underpinning adiposity and inflammation in self-identified Hispanic/Latino populations

Author

Anwar, Mohammad Yaser, Baldassari, Antoine R, Polikowsky, Hannah G, Sitlani, Colleen M, Highland, Heather M, Chami, Nathalie, Chen, Hung-Hsin, Graff, Mariaelisa, Howard, Annie Green, Jung, Su Yon, Petty, Lauren E, Wang, Zhe, Zhu, Wanying, Buyske, Steven, Cheng, Iona, Kaplan, Robert, Kooperberg, Charles, Loos, Ruth JF, Peters, Ulrike, McCormick, Joseph B, Fisher-Hoch, Susan P, Avery, Christy L, Taylor, Kira C, Below, Jennifer E, and North, Kari E

Subjects
Biological Sciences, Genetics, Human Genome, Clinical Research, Obesity, Aetiology, 2.1 Biological and endogenous factors, Adiposity, Genetic Pleiotropy, Hispanic or Latino, Humans, Inflammation, Genetic pleiotropy, Hispanic Americans, Medical Biochemistry and Metabolomics, Oncology and Carcinogenesis, Genetics & Heredity, Medical biochemistry and metabolomics
Abstract

BackgroundConcurrent variation in adiposity and inflammation suggests potential shared functional pathways and pleiotropic disease underpinning. Yet, exploration of pleiotropy in the context of adiposity-inflammation has been scarce, and none has included self-identified Hispanic/Latino populations. Given the high level of ancestral diversity in Hispanic American population, genetic studies may reveal variants that are infrequent/monomorphic in more homogeneous populations.MethodsUsing multi-trait Adaptive Sum of Powered Score (aSPU) method, we examined individual and shared genetic effects underlying inflammatory (CRP) and adiposity-related traits (Body Mass Index [BMI]), and central adiposity (Waist to Hip Ratio [WHR]) in HLA participating in the Population Architecture Using Genomics and Epidemiology (PAGE) cohort (N = 35,871) with replication of effects in the Cameron County Hispanic Cohort (CCHC) which consists of Mexican American individuals.ResultsOf the > 16 million SNPs tested, variants representing 7 independent loci were found to illustrate significant association with multiple traits. Two out of 7 variants were replicated at statistically significant level in multi-trait analyses in CCHC. The lead variant on APOE (rs439401) and rs11208712 were found to harbor multi-trait associations with adiposity and inflammation.ConclusionsResults from this study demonstrate the importance of considering pleiotropy for improving our understanding of the etiology of the various metabolic pathways that regulate cardiovascular disease development.

Published
2022

3. Sleep-disordered breathing is associated with higher carboxymethyllysine level in elderly women but not elderly men in the cardiovascular health study

Author

Ahiawodzi, Peter D, Kerber, Richard A, Taylor, Kira C, Groves, Frank D, O'Brien, Elizabeth, Ix, Joachim H, Kizer, Jorge R, Djoussé, Luc, Tracy, Russell P, Newman, Anne B, Siscovick, David S, Robbins, John, and Mukamal, Kenneth

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Aging, Sleep Research, Cardiovascular, Lung, Good Health and Well Being, Aged, Aged, 80 and over, Cardiovascular Diseases, Case-Control Studies, Female, Humans, Lysine, Male, Oxidative Stress, Sex Factors, Sleep Apnea Syndromes, Carboxymethyl-lysine, advanced glycation end-product, sleep-disordered breathing, oxidative stress, Apnea-Hypopnea Index, Apnea–Hypopnea Index, Environmental Biotechnology, Toxicology, Bioinformatics and computational biology, Medical biotechnology, Environmental biotechnology
Abstract

ContextCarboxymethyl-lysine (CML) results from oxidative stress and has been linked to cardiovascular disease.ObjectiveThe objective of this study is to investigate the association between sleep-disordered breathing (SDB) - a source of oxidative stress - and CML.Materials and methodsAbout 1002 participants in the Cardiovascular Health Study (CHS) were studied.ResultsWomen with SDB had significantly higher CML concentration compared with those without SDB (OR = 1.63, 95%CI = 1.03-2.58, p = 0.04). The association was not significant among men.DiscussionSDB was associated with CML concentration among elderly women but not men in the Cardiovascular Health Study.ConclusionAccumulation of CML may be an adverse health consequence of SDB.

Published
2017

4. A genome-wide association study meta-analysis of clinical fracture in 10,012 African American women

Author

Taylor, Kira C, Evans, Daniel S, Edwards, Digna R Velez, Edwards, Todd L, Sofer, Tamar, Li, Guo, Liu, Youfang, Franceschini, Nora, Jackson, Rebecca D, Giri, Ayush, Donneyong, Macarius, Psaty, Bruce, Rotter, Jerome I, LaCroix, Andrea Z, Jordan, Joanne M, Robbins, John A, Lewis, Beth, Stefanick, Marcia L, Liu, Yongmei, Garcia, Melissa, Harris, Tamara, Cauley, Jane A, and North, Kari E

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Minority Health, Genetics, Human Genome, Aging, Osteoporosis, Musculoskeletal, AA, African American, ASW, African ancestry individuals from Southwest USA, African American, BMD, bone mineral density, BMI, body mass index, BMP, bone morphogenetic protein, CES-D, Center for Epidemiological Studies-Depression scale, CEU, CEPH-Utah, CHS, Cardiovascular Health Study, DNA, deoxyribonucleic acid, EAF, effect allele frequency, Fracture, GEFOS, Genetic Factors of Osteoporosis, GPGE, genetically predicted gene expression, GTEx Project, Genotype-Tissue Expression project, GWAS, genome-wide association study, Genetic association study, Genome-wide association study, JoCoOA, Johnston County Osteoarthritis Project, MAC, minor allele count, MAF, minor allele frequency, Meta-analysis, OF, osteoporotic fracture, RNA, ribonucleic acid, SD, standard deviation, SHARe, SNP Health Association Resource, SNP, single nucleotide polymorphism, WHI, Women's Health Initiative, YRI, Yoruban, Clinical sciences
Abstract

BackgroundOsteoporosis is a major public health problem associated with excess disability and mortality. It is estimated that 50-70% of the variation in osteoporotic fracture risk is attributable to genetic factors. The purpose of this hypothesis-generating study was to identify possible genetic determinants of fracture among African American (AA) women in a GWAS meta-analysis.MethodsData on clinical fractures (all fractures except fingers, toes, face, skull or sternum) were analyzed among AA female participants in the Women's Health Initiative (WHI) (N = 8155), Cardiovascular Health Study (CHS) (N = 504), BioVU (N = 704), Health ABC (N = 651), and the Johnston County Osteoarthritis Project (JoCoOA) (N = 291). Affymetrix (WHI) and Illumina (Health ABC, JoCoOA, BioVU, CHS) GWAS panels were used for genotyping, and a 1:1 ratio of YRI:CEU HapMap haplotypes was used as an imputation reference panel. We used Cox proportional hazard models or logistic regression to evaluate the association of ~ 2.5 million SNPs with fracture risk, adjusting for ancestry, age, and geographic region where applicable. We conducted a fixed-effects, inverse variance-weighted meta-analysis. Genome-wide significance was set at P

Published
2016

5. Risk of Heart Failure Among Postmenopausal Women

Author

Donneyong, Macarius M, Hornung, Carlton A, Taylor, Kira C, Baumgartner, Richard N, Myers, John A, Eaton, Charles B, Gorodeski, Eiran Z, Klein, Liviu, Martin, Lisa W, Shikany, James M, Song, Yiqing, Li, Wenjun, and Manson, JoAnn E

Subjects
Clinical Research, Prevention, Nutrition, Aging, Clinical Trials and Supportive Activities, Complementary and Integrative Health, Cardiovascular, Heart Disease, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Aged, Calcium, Dietary, Dietary Supplements, Exercise, Exercise Test, Female, Follow-Up Studies, Heart Failure, Hemodynamics, Humans, Middle Aged, Postmenopause, Prospective Studies, Treatment Outcome, Vitamin D, Vitamins, Women's Health, calcium, clinical trial, heart failure, vitamin D, women, Biochemistry and Cell Biology, Cardiorespiratory Medicine and Haematology, Medical Physiology, Cardiovascular System & Hematology
Abstract

BackgroundVitamin D supplementation may be an inexpensive intervention to reduce heart failure (HF) incidence. However, there are insufficient data to support this hypothesis. This study evaluates whether vitamin D plus calcium (CaD) supplementation is associated with lower rates of HF in postmenopausal women and whether the effects differ between those at high versus low risk for HF.Methods and resultsAnalyses were restricted to 35 983 (of original 36 282) women aged 50 to 79 years old in the Women's Health Initiative randomized trial of CaD supplementation who were randomized 1:1 in a double-blinded fashion to receive 1000 mg/d of calcium plus 400 IU/d of vitamin D3 or placebo. Overall, 744 adjudicated incident HF cases (intervention, 363; control, 381) occurred during a median follow-up of 7.1 (interquartile range, 1.6) years. CaD supplementation, compared with placebo, was not associated with reduced HF risk in the overall population, hazard ratio, 0.95; P=0.46. However, CaD supplementation had differential effects (P interaction=0.005) in subgroups stratified by baseline risk status of HF defined by the presence (high risk=17 449) or absence (low risk=18 534) of pre-existing HF precursors including coronary heart diseases, diabetes mellitus, or hypertension: 37% (hazard ratio, 0.63 [95% confidence interval, 0.46-0.87]) lower risk of HF in the low-risk versus hazard ratio, 1.06; P=0.51, in the high-risk subgroups.ConclusionsCaD supplementation did not significantly reduce HF incidence in the overall cohort, however, it was beneficial among postmenopausal women without major HF precursors while of little value in high-risk subgroups. Additional studies are warranted to confirm these findings and investigate the underlying mechanism.Clinical trial registration urlhttp://www.clinicaltrials.gov. Unique identifier: NCT00000611.

Published
2015

6. A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry

Author

Monda, Keri L, Chen, Gary K, Taylor, Kira C, Palmer, Cameron, Edwards, Todd L, Lange, Leslie A, Ng, Maggie CY, Adeyemo, Adebowale A, Allison, Matthew A, Bielak, Lawrence F, Chen, Guanjie, Graff, Mariaelisa, Irvin, Marguerite R, Rhie, Suhn K, Li, Guo, Liu, Yongmei, Liu, Youfang, Lu, Yingchang, Nalls, Michael A, Sun, Yan V, Wojczynski, Mary K, Yanek, Lisa R, Aldrich, Melinda C, Ademola, Adeyinka, Amos, Christopher I, Bandera, Elisa V, Bock, Cathryn H, Britton, Angela, Broeckel, Ulrich, Cai, Quiyin, Caporaso, Neil E, Carlson, Chris S, Carpten, John, Casey, Graham, Chen, Wei-Min, Chen, Fang, Chen, Yii-Der I, Chiang, Charleston WK, Coetzee, Gerhard A, Demerath, Ellen, Deming-Halverson, Sandra L, Driver, Ryan W, Dubbert, Patricia, Feitosa, Mary F, Feng, Ye, Freedman, Barry I, Gillanders, Elizabeth M, Gottesman, Omri, Guo, Xiuqing, Haritunians, Talin, Harris, Tamara, Harris, Curtis C, Hennis, Anselm JM, Hernandez, Dena G, McNeill, Lorna H, Howard, Timothy D, Howard, Barbara V, Howard, Virginia J, Johnson, Karen C, Kang, Sun J, Keating, Brendan J, Kolb, Suzanne, Kuller, Lewis H, Kutlar, Abdullah, Langefeld, Carl D, Lettre, Guillaume, Lohman, Kurt, Lotay, Vaneet, Lyon, Helen, Manson, JoAnn E, Maixner, William, Meng, Yan A, Monroe, Kristine R, Morhason-Bello, Imran, Murphy, Adam B, Mychaleckyj, Josyf C, Nadukuru, Rajiv, Nathanson, Katherine L, Nayak, Uma, N'Diaye, Amidou, Nemesure, Barbara, Wu, Suh-Yuh, Leske, M Cristina, Neslund-Dudas, Christine, Neuhouser, Marian, Nyante, Sarah, Ochs-Balcom, Heather, Ogunniyi, Adesola, Ogundiran, Temidayo O, Ojengbede, Oladosu, Olopade, Olufunmilayo I, Palmer, Julie R, Ruiz-Narvaez, Edward A, Palmer, Nicholette D, Press, Michael F, Rampersaud, Evandine, Rasmussen-Torvik, Laura J, Rodriguez-Gil, Jorge L, Salako, Babatunde, and Schadt, Eric E

Subjects
Biological Sciences, Genetics, Human Genome, Black or African American, Body Mass Index, Case-Control Studies, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Obesity, Polymorphism, Single Nucleotide, NABEC Consortium, UKBEC Consortium, BioBank Japan Project, AGEN Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one new locus at 5q33 (GALNT10, rs7708584, P = 3.4 × 10(-11)) and another at 7p15 when we included data from the GIANT consortium (MIR148A-NFE2L3, rs10261878, P = 1.2 × 10(-10)). We also found suggestive evidence of an association at a third locus at 6q16 in the African-ancestry sample (KLHL32, rs974417, P = 6.9 × 10(-8)). Thirty-two of the 36 previously established BMI variants showed directionally consistent effect estimates in our GWAS (binomial P = 9.7 × 10(-7)), five of which reached genome-wide significance. These findings provide strong support for shared BMI loci across populations, as well as for the utility of studying ancestrally diverse populations.

Published
2013

7. 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

10. Association between cigarette smoking and ovarian reserve among women seeking fertility care

Author

Oladipupo, Islamiat, primary, Ali, T’shura, additional, Hein, David W., additional, Pagidas, Kelly, additional, Bohler, Henry, additional, Doll, Mark A., additional, Mann, Merry Lynn, additional, Gentry, Adrienne, additional, Chiang, Jasmine L., additional, Pierson, Rebecca C., additional, Torres, Sashia, additional, Reece, Emily, additional, and Taylor, Kira C., additional

Published
2022
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11. Genetic Pleiotropy Underpinning Adiposity and Inflammation in Self-Identified Hispanic/Latino Populations

Author

Anwar, Mohammad Yaser, primary, Baldassari, Antoine R., additional, Polikowsky, Hannah G., additional, Sitlani, Colleen M., additional, Highland, Heather M., additional, Chami, Nathalie, additional, Chen, Hung-Hsin, additional, Graff, Mariaelisa, additional, Howard, Annie Green, additional, Jung, Su Yon, additional, Petty, Lauren E., additional, Wang, Zhe, additional, Zhu, Wanying, additional, Buyske, Steven, additional, Cheng, Iona, additional, Kaplan, Robert, additional, Kooperberg, Charles, additional, Loos, Ruth J.F., additional, Peters, Ulrike, additional, McCormick, Joseph B., additional, Fisher-Hoch, Susan P., additional, Avery, Christy L, additional, Taylor, Kira C, additional, Below, Jennifer E., additional, and North, Kari E., additional

Published
2022
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12. Association of genomic loci from a cardiovascular gene SNP array with fibrinogen levels in European Americans and African-Americans from six cohort studies: the Candidate Gene Association Resource (CARe)

Author

Wassel, Christina L., Lange, Leslie A., Keating, Brendan J., Taylor, Kira C., Johnson, Andrew D., Palmer, Cameron, Ho, Lindsey A., Smith, Nicholas L., Lange, Ethan M., Li, Yun, Yang, Qiong, Delaney, Joseph A., Tang, Weihong, Tofler, Geoffrey, Redline, Susan, Taylor, Herman A., Jr, Wilson, James G., Tracy, Russell P., Jacobs, David R., Jr, Folsom, Aaron R., Green, David, O'Donnell, Christopher J., and Reiner, Alexander P.

Published
2011
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14. Association Between Cigarette Smoking and Ovarian Reserve Among Women Seeking Fertility Care

Author

Oladipupo, Islamiat, primary, Ali, T'shura, additional, Hein, David W, additional, Pagidas, Kelly, additional, Bohler, Henry, additional, Doll, Mark A, additional, Mann, Merry Lynn, additional, Gentry, Adrienne, additional, Jasmine, Chiang L, additional, Pierson, Rebecca C, additional, Torres, Sashia, additional, Reece, Emily, additional, and Taylor, Kira C, additional

Published
2021
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19. Exposure to volatile organic compounds – acrolein, 1,3-butadiene, and crotonaldehyde – is associated with vascular dysfunction

Author

McGraw, Katlyn E., primary, Riggs, Daniel W., additional, Rai, Shesh, additional, Navas-Acien, Ana, additional, Xie, Zhengzhi, additional, Lorkiewicz, Pawel, additional, Lynch, Jordan, additional, Zafar, Nagma, additional, Krishnasamy, Sathya, additional, Taylor, Kira C., additional, Conklin, Daniel J., additional, DeFilippis, Andrew P., additional, Srivastava, Sanjay, additional, and Bhatnagar, Aruni, additional

Published
2021
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20. Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of European descent confirm known loci and reveal several novel associations

Author

Yoneyama, Sachiko, Guo, Yiran, Lanktree, Matthew B., Barnes, Michael R., Elbers, Clara C., Karczewski, Konrad J, Padmanabhan, Sandosh, Bauer, Florianne, Baumert, Jens, Beitelshees, Amber, Berenson, Gerald S., Boer, Jolanda M.A., Burke, Gregory, Cade, Brian, Chen, Wei, Cooper-Dehoff, Rhonda M., Gaunt, Tom R., Gieger, Christian, Gong, Yan, Gorski, Mathias, Heard-Costa, Nancy, Johnson, Toby, Lamonte, Michael J., Mcdonough, Caitrin, Monda, Keri L., Onland-Moret, Charlotte N., Nelson, Christopher P., OʼConnell, Jeffrey R., Ordovas, Jose, Peter, Inga, Peters, Annette, Shaffer, Jonathan, Shen, Haiqinq, Smith, Erin, Speilotes, Liz, Thomas, Fridtjof, Thorand, Barbara, Verschuren, Monique W. M., Anand, Sonia S., Dominiczak, Anna, Davidson, Karina W., Hegele, Robert A., Heid, Iris, Hofker, Marten H., Huggins, Gordon S., Illig, Thomas, Johnson, Julie A., Kirkland, Susan, König, Wolfgang, Langaee, Taimour Y., Mccaffery, Jeanne, Melander, Olle, Mitchell, Braxton D., Munroe, Patricia, Murray, Sarah S., Papanicolaou, George, Redline, Susan, Reilly, Muredach, Samani, Nilesh J., Schork, Nicholas J., Van Der Schouw, Yvonne T., Shimbo, Daichi, Shuldiner, Alan R., Tobin, Martin D., Wijmenga, Cisca, Yusuf, Salim, Hakonarson, Hakon, Lange, Leslie A., Demerath, Ellen W, Fox, Caroline S., North, Kari E, Reiner, Alex P., Keating, Brendan, and Taylor, Kira C.

Published
2014
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23. A gene-centric association scan for Coagulation Factor VII levels in European and African Americans: the Candidate Gene Association Resource (CARe) Consortium

Author

Taylor, Kira C., Lange, Leslie A., Zabaneh, Delilah, Lange, Ethan, Keating, Brendan J., Tang, Weihong, Smith, Nicholas L., Delaney, Joseph A., Kumari, Meena, Hingorani, Aroon, North, Kari E., Kivimaki, Mika, Tracy, Russell P., OʼDonnell, Christopher J., Folsom, Aaron R., Green, David, Humphries, Steve E., and Reiner, Alexander P.

Published
2011
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26. A genome-wide association study meta-analysis of clinical fracture in 10,012 African American women

Author

Taylor, Kira C., primary, Evans, Daniel S., additional, Edwards, Digna R. Velez, additional, Edwards, Todd L., additional, Sofer, Tamar, additional, Li, Guo, additional, Liu, Youfang, additional, Franceschini, Nora, additional, Jackson, Rebecca D., additional, Giri, Ayush, additional, Donneyong, Macarius, additional, Psaty, Bruce, additional, Rotter, Jerome I., additional, LaCroix, Andrea Z., additional, Jordan, Joanne M., additional, Robbins, John A., additional, Lewis, Beth, additional, Stefanick, Marcia L., additional, Liu, Yongmei, additional, Garcia, Melissa, additional, Harris, Tamara, additional, Cauley, Jane A., additional, and North, Kari E., additional

Published
2016
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27. Risk of heart failure among postmenopausal women: a secondary analysis of the randomized trial of vitamin D plus calcium of the women's health initiative.

Author

Donneyong, Macarius M, Donneyong, Macarius M, Hornung, Carlton A, Taylor, Kira C, Baumgartner, Richard N, Myers, John A, Eaton, Charles B, Gorodeski, Eiran Z, Klein, Liviu, Martin, Lisa W, Shikany, James M, Song, Yiqing, Li, Wenjun, Manson, JoAnn E, Donneyong, Macarius M, Donneyong, Macarius M, Hornung, Carlton A, Taylor, Kira C, Baumgartner, Richard N, Myers, John A, Eaton, Charles B, Gorodeski, Eiran Z, Klein, Liviu, Martin, Lisa W, Shikany, James M, Song, Yiqing, Li, Wenjun, and Manson, JoAnn E

Abstract

BackgroundVitamin D supplementation may be an inexpensive intervention to reduce heart failure (HF) incidence. However, there are insufficient data to support this hypothesis. This study evaluates whether vitamin D plus calcium (CaD) supplementation is associated with lower rates of HF in postmenopausal women and whether the effects differ between those at high versus low risk for HF.Methods and resultsAnalyses were restricted to 35 983 (of original 36 282) women aged 50 to 79 years old in the Women's Health Initiative randomized trial of CaD supplementation who were randomized 1:1 in a double-blinded fashion to receive 1000 mg/d of calcium plus 400 IU/d of vitamin D3 or placebo. Overall, 744 adjudicated incident HF cases (intervention, 363; control, 381) occurred during a median follow-up of 7.1 (interquartile range, 1.6) years. CaD supplementation, compared with placebo, was not associated with reduced HF risk in the overall population, hazard ratio, 0.95; P=0.46. However, CaD supplementation had differential effects (P interaction=0.005) in subgroups stratified by baseline risk status of HF defined by the presence (high risk=17 449) or absence (low risk=18 534) of pre-existing HF precursors including coronary heart diseases, diabetes mellitus, or hypertension: 37% (hazard ratio, 0.63 [95% confidence interval, 0.46-0.87]) lower risk of HF in the low-risk versus hazard ratio, 1.06; P=0.51, in the high-risk subgroups.ConclusionsCaD supplementation did not significantly reduce HF incidence in the overall cohort, however, it was beneficial among postmenopausal women without major HF precursors while of little value in high-risk subgroups. Additional studies are warranted to confirm these findings and investigate the underlying mechanism.Clinical trial registration urlhttp://www.clinicaltrials.gov. Unique identifier: NCT00000611.

Published
2015

28. Gene-centric meta-analyses of 108,912 individuals confirm known body mass index loci and reveal three novel signals

Author

Guo, Yiran, Lanktree, Matthew B., Taylor, Kira C., Hakonarson, Hakon, Lange, Leslie A., Keating, Brendan J., and The IBC 50K SNP Array BMI Consortium

Subjects
Meta-analysis, FOS: Biological sciences, Genetics, Medicine, Single nucleotide polymorphisms, Obesity--Genetic aspects, Adipose tissues--Analysis, Medical sciences, Body mass index
Abstract

Recent genetic association studies have made progress in uncovering components of the genetic architecture of body mass index (BMI). We used the ITMAT-Broad-CARe (IBC) array comprising up to 49,320 single nucleotide polymorphisms (SNPs) across ~2,100 metabolic and cardiovascular-related loci to genotype up to 108,912 individuals of European ancestry (EA), African Americans, Hispanics, and East Asians, from 46 studies, to provide additional insight into SNPs underpinning BMI. We used a five-phase study design: Phase I focused on meta-analysis of EA studies providing individual level genotype data; Phase II performed a replication of cohorts providing summary level EA data; Phase III meta-analyzed results from the first two phases; associated SNPs from Phase III were used for replication in Phase IV; finally in Phase V, a multi-ethnic meta-analysis of all samples from four ethnicities was performed. At an array-wide significance (P

Published
2013
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29. Gene-centric meta-analyses for central adiposity traits in up to 57,412 individuals of European descent confirm known loci and reveal several novel associations

Author

Yoneyama, Sachiko, Guo, Yiran, Lanktree, Matthew B., Barnes, Michael R., Elbers, Clara C., Karczewski, Konrad J., Padmanabhan, Sandosh, Bauer, Florianne, Baumert, Jens, Beitelshees, Amber, Berenson, Gerald S., Boer, Jolanda M.A., Burke, Gregory, Cade, Brian, Chen, Wei, Cooper-DeHoff, Rhonda M., Gaunt, Tom R., Gieger, Christian, Gong, Yan, Gorski, Mathias, Heard-Costa, Nancy, Johnson, Toby, Lamonte, Michael J., Mcdonough, Caitrin, Monda, Keri L., Onland-Moret, N. Charlotte, Nelson, Christopher P., O’Connell, Jeffrey R., Ordovas, Jose, Peter, Inga, Peters, Annette, Shaffer, Jonathan, Shen, Haiqinq, Smith, Erin, Speilotes, Liz, Thomas, Fridtjof, Thorand, Barbara, Verschuren, W. M. Monique, Anand, Sonia S., Dominiczak, Anna, Davidson, Karina W., Hegele, Robert A., Heid, Iris, Hofker, Marten H., Huggins, Gordon S., Illig, Thomas, Johnson, Julie A., Kirkland, Susan, Konig, Wolfgang, Langaee, Taimour Y., Mccaffery, Jeanne, Melander, Olle, Mitchell, Braxton D., Munroe, Patricia, Murray, Sarah S., Papanicolaou, George, Redline, Susan, Reilly, Muredach, Samani, Nilesh J., Schork, Nicholas J., Van Der Schouw, Yvonne T., Shimbo, Daichi, Shuldiner, Alan R., Tobin, Martin D., Wijmenga, Cisca, Yusuf, Salim, Hakonarson, Hakon, Lange, Leslie A., Demerath, Ellen W., Fox, Caroline S., North, Kari E., Reiner, Alex P., Keating, Brendan, Taylor, Kira C., Look AHEAD Research Group, GIANT Consortium, and CARe IBC Consortium

Subjects
Meta-analysis, FOS: Biological sciences, Genetics, Medicine, Obesity--Genetic aspects, Adipose tissues--Analysis, Medical sciences
Abstract

Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes, and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57,412 individuals of European descent from 22 cohorts collaborating with the NHLBI's Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20 to 80. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes ∼50,000 cosmopolitan tagged SNPs across ∼2,100 cardiovascular-related genes. Each trait was modeled as a function of age, study site, and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci for WC were observed. For WHR analyses, three novel loci were significantly associated (P

Published
2013
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30. Genome-Wide Association of Body Fat Distribution in African Ancestry Populations Suggests New Loci

Author

Griffin, Paula J., Adeyemo, Adebowale, Wojczynski, Mary K., Papanicolaou, George J., Shriner, Daniel, Lange, Leslie, Liu, Jiankang, Irvin, Marguerite R., Liu, Simin, Millikan, Robert C., Haritunians, Talin, Chen, Wei-Min, Monda, Keri L., Mosley, Thomas H., Ambrosone, Christine B., Sun, Yan V., Ruiz-Narvaez, Edward A., Xue, Luting, Demerath, Ellen W., Strom, Sara S., Andrews, Jeanette S., Taylor, Kira C., Henderson, Brian E., Vitolins, Mara Z., Li, Guo, Chen, Fang, Nalls, Michael A., Yanek, Lisa R., Liu, Ching-Ti, Guo, Xiuqing, Palmas, Walter, and Ellis, Jaclyn C.

Subjects
nutritional and metabolic diseases
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
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31. Investigation of gene-by-sex interactions for lipid traits in diverse populations from the population architecture using genomics and epidemiology study

Author

Quibrera, P Miguel, Taylor, Kira C, North, Kari, and Franceschini, Nora

Subjects
lipids (amino acids, peptides, and proteins)
Abstract

Background High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels are influenced by both genes and the environment. Genome-wide association studies (GWAS) have identified ~100 common genetic variants associated with HDL-C, LDL-C, and/or TG levels, mostly in populations of European descent, but little is known about the modifiers of these associations. Here, we investigated whether GWAS-identified SNPs for lipid traits exhibited heterogeneity by sex in the Population Architecture using Genomics and Epidemiology (PAGE) study. Results A sex-stratified meta-analysis was performed for 49 GWAS-identified SNPs for fasting HDL-C, LDL-C, and ln(TG) levels among adults self-identified as European American (25,013). Heterogeneity by sex was established when phet

Published
2013
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32. Whole-Exome Sequencing Identifies Rare and Low-Frequency Coding Variants Associated with LDL Cholesterol

Author

Lange, Leslie A., primary, Hu, Youna, additional, Zhang, He, additional, Xue, Chenyi, additional, Schmidt, Ellen M., additional, Tang, Zheng-Zheng, additional, Bizon, Chris, additional, Lange, Ethan M., additional, Smith, Joshua D., additional, Turner, Emily H., additional, Jun, Goo, additional, Kang, Hyun Min, additional, Peloso, Gina, additional, Auer, Paul, additional, Li, Kuo-ping, additional, Flannick, Jason, additional, Zhang, Ji, additional, Fuchsberger, Christian, additional, Gaulton, Kyle, additional, Lindgren, Cecilia, additional, Locke, Adam, additional, Manning, Alisa, additional, Sim, Xueling, additional, Rivas, Manuel A., additional, Holmen, Oddgeir L., additional, Gottesman, Omri, additional, Lu, Yingchang, additional, Ruderfer, Douglas, additional, Stahl, Eli A., additional, Duan, Qing, additional, Li, Yun, additional, Durda, Peter, additional, Jiao, Shuo, additional, Isaacs, Aaron, additional, Hofman, Albert, additional, Bis, Joshua C., additional, Correa, Adolfo, additional, Griswold, Michael E., additional, Jakobsdottir, Johanna, additional, Smith, Albert V., additional, Schreiner, Pamela J., additional, Feitosa, Mary F., additional, Zhang, Qunyuan, additional, Huffman, Jennifer E., additional, Crosby, Jacy, additional, Wassel, Christina L., additional, Do, Ron, additional, Franceschini, Nora, additional, Martin, Lisa W., additional, Robinson, Jennifer G., additional, Assimes, Themistocles L., additional, Crosslin, David R., additional, Rosenthal, Elisabeth A., additional, Tsai, Michael, additional, Rieder, Mark J., additional, Farlow, Deborah N., additional, Folsom, Aaron R., additional, Lumley, Thomas, additional, Fox, Ervin R., additional, Carlson, Christopher S., additional, Peters, Ulrike, additional, Jackson, Rebecca D., additional, van Duijn, Cornelia M., additional, Uitterlinden, André G., additional, Levy, Daniel, additional, Rotter, Jerome I., additional, Taylor, Herman A., additional, Gudnason, Vilmundur, additional, Siscovick, David S., additional, Fornage, Myriam, additional, Borecki, Ingrid B., additional, Hayward, Caroline, additional, Rudan, Igor, additional, Chen, Y. Eugene, additional, Bottinger, Erwin P., additional, Loos, Ruth J.F., additional, Sætrom, Pål, additional, Hveem, Kristian, additional, Boehnke, Michael, additional, Groop, Leif, additional, McCarthy, Mark, additional, Meitinger, Thomas, additional, Ballantyne, Christie M., additional, Gabriel, Stacey B., additional, O’Donnell, Christopher J., additional, Post, Wendy S., additional, North, Kari E., additional, Reiner, Alexander P., additional, Boerwinkle, Eric, additional, Psaty, Bruce M., additional, Altshuler, David, additional, Kathiresan, Sekar, additional, Lin, Dan-Yu, additional, Jarvik, Gail P., additional, Cupples, L. Adrienne, additional, Kooperberg, Charles, additional, Wilson, James G., additional, Nickerson, Deborah A., additional, Abecasis, Goncalo R., additional, Rich, Stephen S., additional, Tracy, Russell P., additional, Willer, Cristen J., additional, Altshuler, David M., additional, Abecasis, Gonçalo R., additional, Allayee, Hooman, additional, Cresci, Sharon, additional, Daly, Mark J., additional, de Bakker, Paul I.W., additional, DePristo, Mark A., additional, Donnelly, Peter, additional, Fennell, Tim, additional, Garimella, Kiran, additional, Hazen, Stanley L., additional, Jordan, Daniel M., additional, Kiezun, Adam, additional, Lettre, Guillaume, additional, Li, Bingshan, additional, Li, Mingyao, additional, Newton-Cheh, Christopher H., additional, Padmanabhan, Sandosh, additional, Pulit, Sara, additional, Rader, Daniel J., additional, Reich, David, additional, Reilly, Muredach P., additional, Schwartz, Steve, additional, Scott, Laura, additional, Spertus, John A., additional, Stitziel, Nathaniel O., additional, Stoletzki, Nina, additional, Sunyaev, Shamil R., additional, Voight, Benjamin F., additional, Akylbekova, Ermeg, additional, Atwood, Larry D., additional, Barbalic, Maja, additional, Barr, R. Graham, additional, Benjamin, Emelia J., additional, Bis, Joshua, additional, Bowden, Donald W., additional, Brody, Jennifer, additional, Budoff, Matthew, additional, Burke, Greg, additional, Buxbaum, Sarah, additional, Carr, Jeff, additional, Chen, Donna T., additional, Chen, Ida Y., additional, Chen, Wei-Min, additional, Concannon, Pat, additional, D’Agostino, Ralph, additional, DeStefano, Anita L., additional, Dreisbach, Albert, additional, Dupuis, Josée, additional, Durda, J. Peter, additional, Ellis, Jaclyn, additional, Fox, Caroline S., additional, Fox, Ervin, additional, Funari, Vincent, additional, Ganesh, Santhi K., additional, Gardin, Julius, additional, Goff, David, additional, Gordon, Ora, additional, Grody, Wayne, additional, Gross, Myron, additional, Guo, Xiuqing, additional, Hall, Ira M., additional, Heard-Costa, Nancy L., additional, Heckbert, Susan R., additional, Heintz, Nicholas, additional, Herrington, David M., additional, Hickson, DeMarc, additional, Huang, Jie, additional, Hwang, Shih-Jen, additional, Jacobs, David R., additional, Jenny, Nancy S., additional, Johnson, Andrew D., additional, Johnson, Craig W., additional, Kawut, Steven, additional, Kronmal, Richard, additional, Kurz, Raluca, additional, Lange, Leslie A., additional, Larson, Martin G., additional, Lawson, Mark, additional, Lewis, Cora E., additional, Li, Dalin, additional, Lin, Honghuang, additional, Liu, Chunyu, additional, Liu, Jiankang, additional, Liu, Kiang, additional, Liu, Xiaoming, additional, Liu, Yongmei, additional, Longstreth, William T., additional, Loria, Cay, additional, Lunetta, Kathryn, additional, Mackey, Aaron J., additional, Mackey, Rachel, additional, Manichaikul, Ani, additional, Maxwell, Taylor, additional, McKnight, Barbara, additional, Meigs, James B., additional, Morrison, Alanna C., additional, Musani, Solomon K., additional, Mychaleckyj, Josyf C., additional, Nettleton, Jennifer A., additional, North, Kari, additional, O’Leary, Daniel, additional, Ong, Frank, additional, Palmas, Walter, additional, Pankow, James S., additional, Pankratz, Nathan D., additional, Paul, Shom, additional, Perez, Marco, additional, Person, Sharina D., additional, Polak, Joseph, additional, Quinlan, Aaron R., additional, Raffel, Leslie J., additional, Ramachandran, Vasan S., additional, Rice, Kenneth, additional, Sanders, Jill P., additional, Schreiner, Pamela, additional, Seshadri, Sudha, additional, Shea, Steve, additional, Sidney, Stephen, additional, Silverstein, Kevin, additional, Smith, Nicholas L., additional, Sotoodehnia, Nona, additional, Srinivasan, Asoke, additional, Taylor, Kent, additional, Thomas, Fridtjof, additional, Tsai, Michael Y., additional, Volcik, Kelly A., additional, Wassel, Chrstina L., additional, Watson, Karol, additional, Wei, Gina, additional, White, Wendy, additional, Wiggins, Kerri L., additional, Wilk, Jemma B., additional, Williams, O. Dale, additional, Wilson, Gregory, additional, Wolf, Phillip, additional, Zakai, Neil A., additional, Hardy, John, additional, Meschia, James F., additional, Nalls, Michael, additional, Singleton, Andrew, additional, Worrall, Brad, additional, Bamshad, Michael J., additional, Barnes, Kathleen C., additional, Abdulhamid, Ibrahim, additional, Accurso, Frank, additional, Anbar, Ran, additional, Beaty, Terri, additional, Bigham, Abigail, additional, Black, Phillip, additional, Bleecker, Eugene, additional, Buckingham, Kati, additional, Cairns, Anne Marie, additional, Caplan, Daniel, additional, Chatfield, Barbara, additional, Chidekel, Aaron, additional, Cho, Michael, additional, Christiani, David C., additional, Crapo, James D., additional, Crouch, Julia, additional, Daley, Denise, additional, Dang, Anthony, additional, Dang, Hong, additional, De Paula, Alicia, additional, DeCelie-Germana, Joan, additional, Drumm, Allen DozorMitch, additional, Dyson, Maynard, additional, Emerson, Julia, additional, Emond, Mary J., additional, Ferkol, Thomas, additional, Fink, Robert, additional, Foster, Cassandra, additional, Froh, Deborah, additional, Gao, Li, additional, Gershan, William, additional, Gibson, Ronald L., additional, Godwin, Elizabeth, additional, Gondor, Magdalen, additional, Gutierrez, Hector, additional, Hansel, Nadia N., additional, Hassoun, Paul M., additional, Hiatt, Peter, additional, Hokanson, John E., additional, Howenstine, Michelle, additional, Hummer, Laura K., additional, Kanga, Jamshed, additional, Kim, Yoonhee, additional, Knowles, Michael R., additional, Konstan, Michael, additional, Lahiri, Thomas, additional, Laird, Nan, additional, Lange, Christoph, additional, Lin, Lin, additional, Lin, Xihong, additional, Louie, Tin L., additional, Lynch, David, additional, Make, Barry, additional, Martin, Thomas R., additional, Mathai, Steve C., additional, Mathias, Rasika A., additional, McNamara, John, additional, McNamara, Sharon, additional, Meyers, Deborah, additional, Millard, Susan, additional, Mogayzel, Peter, additional, Moss, Richard, additional, Murray, Tanda, additional, Nielson, Dennis, additional, Noyes, Blakeslee, additional, O’Neal, Wanda, additional, Orenstein, David, additional, O’Sullivan, Brian, additional, Pace, Rhonda, additional, Pare, Peter, additional, Parker, H. Worth, additional, Passero, Mary Ann, additional, Perkett, Elizabeth, additional, Prestridge, Adrienne, additional, Rafaels, Nicholas M., additional, Ramsey, Bonnie, additional, Regan, Elizabeth, additional, Ren, Clement, additional, Retsch-Bogart, George, additional, Rock, Michael, additional, Rosen, Antony, additional, Rosenfeld, Margaret, additional, Ruczinski, Ingo, additional, Sanford, Andrew, additional, Schaeffer, David, additional, Sell, Cindy, additional, Sheehan, Daniel, additional, Silverman, Edwin K., additional, Sin, Don, additional, Spencer, Terry, additional, Stonebraker, Jackie, additional, Tabor, Holly K., additional, Varlotta, Laurie, additional, Vergara, Candelaria I., additional, Weiss, Robert, additional, Wigley, Fred, additional, Wise, Robert A., additional, Wright, Fred A., additional, Wurfel, Mark M., additional, Zanni, Robert, additional, Zou, Fei, additional, Green, Phil, additional, Shendure, Jay, additional, Akey, Joshua M., additional, Bustamante, Carlos D., additional, Eichler, Evan E., additional, Fox, P. Keolu, additional, Fu, Wenqing, additional, Gordon, Adam, additional, Gravel, Simon, additional, Johnsen, Jill M., additional, Kan, Mengyuan, additional, Kenny, Eimear E., additional, Kidd, Jeffrey M., additional, Lara-Garduno, Fremiet, additional, Leal, Suzanne M., additional, Liu, Dajiang J., additional, McGee, Sean, additional, O’Connor, Timothy D., additional, Paeper, Bryan, additional, Robertson, Peggy D., additional, Staples, Jeffrey C., additional, Tennessen, Jacob A., additional, Wang, Gao, additional, Yi, Qian, additional, Jackson, Rebecca, additional, Anderson, Garnet, additional, Anton-Culver, Hoda, additional, Auer, Paul L., additional, Beresford, Shirley, additional, Black, Henry, additional, Brunner, Robert, additional, Brzyski, Robert, additional, Burwen, Dale, additional, Caan, Bette, additional, Carty, Cara L., additional, Chlebowski, Rowan, additional, Cummings, Steven, additional, Curb, J. David, additional, Eaton, Charles B., additional, Ford, Leslie, additional, Fullerton, Stephanie M., additional, Gass, Margery, additional, Geller, Nancy, additional, Heiss, Gerardo, additional, Howard, Barbara V., additional, Hsu, Li, additional, Hutter, Carolyn M., additional, Ioannidis, John, additional, Johnson, Karen C., additional, Kuller, Lewis, additional, LaCroix, Andrea, additional, Lakshminarayan, Kamakshi, additional, Lane, Dorothy, additional, Lasser, Norman, additional, LeBlanc, Erin, additional, Li, Kuo-Ping, additional, Limacher, Marian, additional, Logsdon, Benjamin A., additional, Ludlam, Shari, additional, Manson, JoAnn E., additional, Margolis, Karen, additional, Martin, Lisa, additional, McGowan, Joan, additional, Monda, Keri L., additional, Kotchen, Jane Morley, additional, Nathan, Lauren, additional, Ockene, Judith, additional, O’Sullivan, Mary Jo, additional, Phillips, Lawrence S., additional, Prentice, Ross L., additional, Robbins, John, additional, Rossouw, Jacques E., additional, Sangi-Haghpeykar, Haleh, additional, Sarto, Gloria E., additional, Shumaker, Sally, additional, Simon, Michael S., additional, Stefanick, Marcia L., additional, Stein, Evan, additional, Tang, Hua, additional, Taylor, Kira C., additional, Thomson, Cynthia A., additional, Thornton, Timothy A., additional, Van Horn, Linda, additional, Vitolins, Mara, additional, Wactawski-Wende, Jean, additional, Wallace, Robert, additional, Wassertheil-Smoller, Sylvia, additional, Zeng, Donglin, additional, Applebaum-Bowden, Deborah, additional, Feolo, Michael, additional, Gan, Weiniu, additional, Paltoo, Dina N., additional, Sholinsky, Phyliss, additional, and Sturcke, Anne, additional

Published
2014
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33. Investigation of gene-by-sex interactions for lipid traits in diverse populations from the population architecture using genomics and epidemiology study.

Author

Taylor, Kira C., Carty, Cara L., Dumitrescu, Logan, Bůžková, Petra, Cole, Shelley A., Hindorff, Lucia, Schumacher, Fred R., Wilkens, Lynne R., Shohet, Ralph V., Miguel Quibrera, P., Johnson, Karen C., Henderson, Brian E., Haessler, Jeff, Franceschini, Nora, Eaton, Charles B., Duggan, David J., Cochran, Barbara, Cheng, Iona, Carlson, Chris S., and Brown-Gentry, Kristin

Subjects
*TRIGLYCERIDES, *HUMAN genetic variation, *EPIDEMIOLOGICAL research, *GENOMICS, *HETEROGENEITY, *EUROPEAN Americans
Abstract

Background: High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels are influenced by both genes and the environment. Genome-wide association studies (GWAS) have identified ∼100 common genetic variants associated with HDL-C, LDL-C, and/or TG levels, mostly in populations of European descent, but little is known about the modifiers of these associations. Here, we investigated whether GWAS-identified SNPs for lipid traits e×hibited heterogeneity by se× in the Population Architecture using Genomics and Epidemiology (PAGE) study. Results: A se×-stratified meta-analysis was performed for 49 GWAS-identified SNPs for fasting HDL-C, LDL-C, and ln (TG) levels among adults self-identified as European American (25,013). Heterogeneity by se× was established when phet < 0.001. There was evidence for heterogeneity by se× for two SNPs for ln(TG) in the APOA1/C3/A4/A5/BUD13 gene cluster: rs28927680 (phet = 7.4×10-7) and rs3135506 (phet = 4.3×10-4), one SNP in PLTP for HDL levels (rs7679; phet = 9.9×10-4), and one in HMGCR for LDL levels (rs12654264; phet = 3.1×10-5). We replicated heterogeneity by se× in five of seventeen loci previously reported by genome-wide studies (binomial p = 0.0009). We also present results for other racial/ethnic groups in the supplementary materials, to provide a resource for future meta-analyses. Conclusions: We provide further evidence for se×-specific effects of SNPs in the APOA1/C3/A4/A5/BUD13 gene cluster, PLTP, and HMGCR on fasting triglyceride levels in European Americans from the PAGE study. Our findings emphasize the need for considering conte×t-specific effects when interpreting genetic associations emerging from GWAS, and also highlight the difficulties in replicating interaction effects across studies and across racial/ethnic groups. [ABSTRACT FROM AUTHOR]

Published
2013
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34. A Meta-Analysis Identifies New Loci Associated with Body Mass index in Individuals of African Ancestry

Author

Monda, Keri L., Chen, Gary K., Taylor, Kira C., Palmer, Cameron, Edwards, Todd L., Lange, Leslie A., Ng, Maggie C.Y., Adeyemo, Adebowale A., Allison, Matthew A., Bielak, Lawrence F., Chen, Guanji, Graff, Mariaelisa, Irvin, Marguerite R., Rhie, Suhn K., Li, Guo, Liu, Yongmei, Liu, Youfang, Lu, Yingchang, Nalls, Michael A., Sun, Yan V., Wojczynski, Mary K., Yanek, Lisa R., Aldrich, Melinda C., Ademola, Adeyinka, Amos, Christopher I., Bandera, Elisa V., Bock, Cathryn H., Britton, Angela, Broeckel, Ulrich, Cai, Quiyin, Caporaso, Neil E., Carlson, Chris, Carpten, John, Casey, Graham, Chen, Wei-Min, Chen, Fang, Chen, Yii-Der I., Chiang, Charleston W.K., Coetzee, Gerhard A., Demerath, Ellen, Deming-Halverson, Sandra L., Driver, Ryan W., Dubbert, Patricia, Feitosa, Mary F., Freedman, Barry I., Gillanders, Elizabeth M., Gottesman, Omri, Guo, Xiuqing, Haritunians, Talin, Harris, Tamara, Harris, Curtis C., Hennis, Anselm JM, Hernandez, Dena G., McNeill, Lorna H., Howard, Timothy D., Howard, Barbara V., Howard, Virginia J., Johnson, Karen C., Kang, Sun J., Keating, Brendan J., Kolb, Suzanne, Kuller, Lewis H., Kutlar, Abdullah, Langefeld, Carl D., Lettre, Guillaume, Lohman, Kurt, Lotay, Vaneet, Lyon, Helen, Manson, JoAnn E., Maixner, William, Meng, Yan A., Monroe, Kristine R., Morhason-Bello, Imran, Murphy, Adam B., Mychaleckyj, Josyf C., Nadukuru, Rajiv, Nathanson, Katherine L., Nayak, Uma, N’Diaye, Amidou, Nemesure, Barbara, Wu, Suh-Yuh, Leske, M. Cristina, Neslund-Dudas, Christine, Neuhouser, Marian, Nyante, Sarah, Ochs-Balcom, Heather, Ogunniyi, Adesola, Ogundiran, Temidayo O., Ojengbede, Oladosu, Olopade, Olufunmilayo I., Palmer, Julie R., Ruiz-Narvaez, Edward A., Palmer, Nicholette D., Press, Michael F., Rampersaud, Evandine, Rasmussen-Torvik, Laura J., Rodriguez-Gil, Jorge L., Salako, Babatunde, Schadt, Eric E., Schwartz, Ann G., Shriner, Daniel A., Siscovick, David, Smith, Shad B., Wassertheil-Smoller, Sylvia, Speliotes, Elizabeth K., Spitz, Margaret R., Sucheston, Lara, Taylor, Herman, Tayo, Bamidele O., Tucker, Margaret A., Van Den Berg, David J., Velez Edwards, Digna R., Wang, Zhaoming, Wiencke, John K., Winkler, Thomas W., Witte, John S., Wrensch, Margaret, Wu, Xifeng, Yang, James J., Levin, Albert M., Young, Taylor R., Zakai, Neil A., Cushman, Mary, Zanetti, Krista A., Zhao, Jing Hua, Zhao, Wei, Zheng, Yonglan, Zhou, Jie, Ziegler, Regina G., Zmuda, Joseph M., Fernandes, Jyotika K., Gilkeson, Gary S., Kamen, Diane L., Hunt, Kelly J., Spruill, Ida J., Ambrosone, Christine B., Ambs, Stefan, Arnett, Donna K., Atwood, Larry, Becker, Diane M., Berndt, Sonja I., Bernstein, Leslie, Blot, William J., Borecki, Ingrid B., Bottinger, Erwin P., Bowden, Donald W., Burke, Gregory, Chanock, Stephen J., Cooper, Richard S., Ding, Jingzhong, Duggan, David, Evans, Michele K., Fox, Caroline, Garvey, W. Timothy, Bradfield, Jonathan P., Hakonarson, Hakon, Grant, Struan F.A., Hsing, Ann, Chu, Lisa, Hu, Jennifer J., Huo, Dezheng, Ingles, Sue A., John, Esther M., Jordan, Joanne M., Kabagambe, Edmond K., Kardia, Sharon L.R., Kittles, Rick A., Goodman, Phyllis J., Klein, Eric A., Kolonel, Laurence N., Le Marchand, Loic, Liu, Simin, McKnight, Barbara, Millikan, Robert C., Mosley, Thomas H., Padhukasahasram, Badri, Williams, L. Keoki, Patel, Sanjay R., Peters, Ulrike, Pettaway, Curtis A., Peyser, Patricia A., Psaty, Bruce M., Redline, Susan, Rotimi, Charles N., Rybicki, Benjamin A., Sale, Michèle M., Schreiner, Pamela J., Signorello, Lisa B., Singleton, Andrew B., Stanford, Janet L., Strom, Sara S., Thun, Michael J., Vitolins, Mara, Zheng, Wei, Moore, Jason H., Williams, Scott M., Zhu, Xiaofeng, Zonderman, Alan B., Kooperberg, Charles, Papanicolaou, George, Henderson, Brian E., Reiner, Alex P., Hirschhorn, Joel N., Loos, Ruth JF, North, Kari E., and Haiman, Christopher A.

Abstract

Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry, and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one novel locus at 5q33 (GALNT10, rs7708584, p=3.4×10−11) and another at 7p15 when combined with data from the Giant consortium (MIR148A/NFE2L3, rs10261878, p=1.2×10−10). We also found suggestive evidence of an association at a third locus at 6q16 in the African ancestry sample (KLHL32, rs974417, p=6.9×10−8). Thirty-two of the 36 previously established BMI variants displayed directionally consistent effect estimates in our GWAS (binomial p=9.7×10−7), of which five reached genome-wide significance. These findings provide strong support for shared BMI loci across populations as well as for the utility of studying ancestrally diverse populations.

Published
2013
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35. 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 R., 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 L. R., 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 F. A., 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
2. Zero hunger, Molecular biology, Epidemiology, African Americans--Health and hygiene, FOS: Biological sciences, Genetics, nutritional and metabolic diseases, Genomics, Obesity--Genetic aspects, Gene mapping
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

36. The anatomical outcome of robotic sacrocolpopexy for treatment of pelvic organ prolapse: a comparison of obese and non-obese patients.

Author

Azadi A, Francis SL, Taylor KC, Diaz SI, Pasic R, Yeganeh T, and Ostergard DR

Subjects
Body Mass Index, Female, Humans, Middle Aged, Obesity complications, Pelvic Organ Prolapse complications, Retrospective Studies, Pelvic Organ Prolapse physiopathology, Pelvic Organ Prolapse surgery, Robotic Surgical Procedures methods, Robotic Surgical Procedures statistics & numerical data
Abstract

The purpose of this study is to compare the anatomical outcome of robotic sacrocolpopexy for pelvic organ prolapse in women with a body mass index (BMI) of 30 and higher to those with a BMI under 30. This is a retrospective chart review. POP-Q measurements preoperatively and 12 months postoperatively were evaluated using non-parametric statistical analysis. The primary outcome was to compare postoperative POPQ measurements at 12 months following surgery. Secondary outcomes were age at the time of surgery, mesh erosion rate, blood loss, length of hospital stay, and baseline anatomical support. A total of 71 patients were identified: 44 patients had a BMI below 30, and 27 had a BMI equal to or greater than 30. We found no significant relationship between BMI and anatomical support at 12 months post operation. However, obese patients were younger at the time of prolapse surgery (53.6 versus 60.6 years of age, p=0.0022). In regards to the ICS prolapse stage, no difference was found between obese and non-obese patients (2.81 versus 2.95, p=0.17).

Published
2014

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