Journal Club Discov EHR Collaboration CHARGE Lu Camp

Journal Club Discov. EHR Collaboration; CHARGE; Lu. Camp; Pro. Di. GY; Go. T 2 D; ESP; SIGMA-T 2 D; T 2 D-GENES; AMP-T 2 D-GENES, Altshuler D, Burtt NP, Scott LJ, Morris AP, Florez JC, Mc. Carthy MI, Boehnke M. et al. Exome sequencing of 20, 791 cases of type 2 diabetes and 24, 440 controls. Nature. 2019 Jun; 570(7759): 71 -76. doi: 10. 1038/s 41586 -019 -1231 -2. Roberto CA, Lawman HG, Le. Vasseur MT, Mitra N, Peterhans A, Herring B, Bleich SN. Association of a Beverage Tax on Sugar-Sweetened and Artificially Sweetened Beverages With Changes in Beverage Prices and Sales at Chain Retailers in a Large Urban Setting. JAMA. 2019 May 14; 321(18): 1799 -1810. doi: 10. 1001/jama. 2019. 4249. 2019年 6月13日　8: 30 -8: 55 ４階　カンファレンス室 埼玉医科大学　総合医療センター　内分泌・糖尿病内科 Department of Endocrinology and Diabetes, Saitama Medical Center, Saitama Medical University 松田　昌文　 Matsuda, Masafumi

2015年 7月24日 Journal Club 22カ国の 300人強の研究者が、欧州、南アジアおよび東アジア、米国、アフリカに祖先をもつ 12万人強の成人 を対象に、全ゲノムまたはエクソーム(タンパク質をコードする遺伝子情報)の解析 Christian Fuchsberger, Jason Flannick, Tanya M. Teslovich, Anubha Mahajan, Vineeta Agarwala, Kyle J. Gaulton, Clement Ma, Pierre Fontanillas, Loukas Moutsianas, Davis J. Mc. Carthy, Manuel A. Rivas, John R. B. Perry, Xueling Sim, Thomas W. Blackwell, Neil R. Robertson, N. William Rayner, Pablo Cingolani, Adam E. Locke, Juan Fernandez Tajes, Heather M. Highland, Josee Dupuis, Peter S. Chines, Cecilia M. Lindgren, Christopher Hartl, Anne U. Jackson, Han Chen, Jeroen R. Huyghe, Martijn van de Bunt, Richard D. Pearson, Ashish Kumar, Martina Müller-Nurasyid, Niels Grarup, Heather M. Stringham, Eric R. Gamazon, Jaehoon Lee, Yuhui Chen, Robert A. Scott, Jennifer E. Below, Peng Chen, Jinyan Huang, Min Jin Go, Michael L. Stitzel, Dorota Pasko, Stephen C. J. Parker, Tibor V. Varga, Todd Green, Nicola L. Beer, Aaron G. Day-Williams, Teresa Ferreira, Tasha Fingerlin, Momoko Horikoshi, Cheng Hu, Iksoo Huh, Mohammad Kamran Ikram, Bong-Jo Kim, Yongkang Kim, Young Jin Kim, Min. Seok Kwon, Juyoung Lee, Selyeong Lee, Keng-Han Lin, Taylor J. Maxwell, Yoshihiko Nagai, Xu Wang, Ryan P. Welch, Joon Yoon, Weihua Zhang, Nir Barzilai, Benjamin F. Voight, Bok-Ghee Han, Christopher P. Jenkinson, Teemu Kuulasmaa, Johanna Kuusisto, Alisa Manning, Maggie C. Y. Ng, Nicholette D. Palmer, Beverley Balkau, Alena Stančáková, Hanna E. Abboud, Heiner Boeing, Vilmantas Giedraitis, Dorairaj Prabhakaran, Omri Gottesman, James Scott, Jason Carey, Phoenix Kwan, George Grant, Joshua D. Smith, Benjamin M. Neale, Shaun Purcell, Adam S. Butterworth, Joanna M. M. Howson, Heung Man Lee, Yingchang Lu, Soo-Heon Kwak, Wei Zhao, John Danesh, Vincent K. L. Lam, Kyong Soo Park, Danish Saleheen, Wing Yee So, Claudia H. T. Tam, Uzma Afzal, David Aguilar, Rector Arya, Tin Aung, Edmund Chan, Carmen Navarro, Ching-Yu Cheng, Domenico Palli, Adolfo Correa, Joanne E. Curran, Denis Rybin, Vidya S. Farook, Sharon P. Fowler, Barry I. Freedman, Michael Griswold, Daniel Esten Hale, Pamela J. Hicks, Chiea-Chuen Khor, Satish Kumar, Benjamin Lehne, Dorothée Thuillier, Wei Yen Lim, Jianjun Liu, Yvonne T. van der Schouw, Marie Loh, Solomon K. Musani, Sobha Puppala, William R. Scott, Loïc Yengo, Sian-Tsung Tan, Herman A. Taylor Jr. , Farook Thameem, Gregory Wilson, Tien Yin Wong, Pål Rasmus Njølstad, Jonathan C. Levy, Massimo Mangino, Lori L. Bonnycastle, Thomas Schwarzmayr, João Fadista, Gabriela L. Surdulescu, Christian Herder, Christopher J. Groves, Thomas Wieland, Jette Bork-Jensen, Ivan Brandslund, Cramer Christensen, Heikki A. Koistinen, Alex S. F. Doney, Leena Kinnunen, Tõnu Esko, Andrew J. Farmer, Liisa Hakaste, Dylan Hodgkiss, Jasmina Kravic, Valeriya Lyssenko, Mette Hollensted, Marit E. Jørgensen, Torben Jørgensen, Claes Ladenvall, Johanne Marie Justesen, Annemari Käräjämäki, Jennifer Kriebel, Wolfgang Rathmann, Lars Lannfelt, Torsten Lauritzen, Narisu, Allan Linneberg, Olle Melander, Lili Milani, Matt Neville, Marju Orho-Melander, Lu Qi, Qibin Qi, Michael Roden, Olov Rolandsson, Amy Swift, Anders H. Rosengren, Kathleen Stirrups, Andrew R. Wood, Evelin Mihailov, Christine Blancher, Mauricio O. Carneiro, Jared Maguire, Ryan Poplin, Khalid Shakir, Timothy Fennell, Mark De. Pristo, Martin Hrabé de Angelis, Panos Deloukas, Anette P. Gjesing, Goo Jun, Peter Nilsson, Jacquelyn Murphy, Robert Onofrio, Barbara Thorand, Torben Hansen, Christa Meisinger, Frank B. Hu, Bo Isomaa, Fredrik Karpe, Liming Liang, Annette Peters, Cornelia Huth, Stephen P. O’Rahilly, Colin N. A. Palmer, Oluf Pedersen, Rainer Rauramaa, Jaakko Tuomilehto, Veikko Salomaa, Richard M. Watanabe, Ann-Christine Syvänen, Richard N. Bergman, Dwaipayan Bharadwaj, Erwin P. Bottinger, Yoon Shin Cho, Giriraj R. Chandak, Juliana C. N. Chan, Kee Seng Chia, Mark J. Daly, Shah B. Ebrahim, Claudia Langenberg, Paul Elliott, Kathleen A. Jablonski, Donna M. Lehman, Weiping Jia, Ronald C. W. Ma, Toni I. Pollin, Manjinder Sandhu, Nikhil Tandon, Philippe Froguel, Inês Barroso, Yik Ying Teo, Eleftheria Zeggini, Ruth J. F. Loos, Kerrin S. Small, Janina S. Ried, Ralph A. De. Fronzo, Harald Grallert, Benjamin Glaser, Andres Metspalu, Nicholas J. Wareham, Mark Walker, Eric Banks, Christian Gieger, Erik Ingelsson, Hae Kyung Im, Thomas Illig, Paul W. Franks, Gemma Buck, Joseph Trakalo, David Buck, Inga Prokopenko, Reedik Mägi, Lars Lind, Yossi Farjoun, Katharine R. Owen, Anna L. Gloyn, Konstantin Strauch, Tiinamaija Tuomi, Jaspal Singh Kooner, Jong-Young Lee, Taesung Park, Peter Donnelly, Andrew D. Morris, Andrew T. Hattersley, Donald W. Bowden, Francis S. Collins, Gil Atzmon, John C. Chambers, Timothy D. Spector, Markku Laakso, Tim M. Strom, Graeme I. Bell, John Blangero, Ravindranath Duggirala, E. Shyong Tai, Gilean Mc. Vean, Craig L. Hanis, James G. Wilson, Mark Seielstad, Timothy M. Frayling, James B. Meigs, Nancy J. Cox, Rob Sladek, Eric S. Lander, Stacey Gabriel, Noël P. Burtt, Karen L. Mohlke, Thomas Meitinger, Leif Groop, Goncalo Abecasis, Jose C. Florez, Laura J. Scott, Andrew P. Morris, Hyun Min Kang, Michael Boehnke, David Altshuler & Mark I. Mc. Carthy Nature. 2016 Jul 11. doi: 10. 1038/nature 18642.

The exome is the part of the genome composed of exons, the sequences which, when transcribed, remain within the mature RNA after introns are removed by RNA splicing and contribute to the final protein product encoded by that gene. Exome sequencing has proved to be an efficient strategy to determine the genetic basis of more than two dozen Mendelian or single gene disorders. https: //en. wikipedia. org/wiki/Exome

Jason Flannick, Josep M. Mercader, Christian Fuchsberger, Miriam S. Udler, Anubha Mahajan, Jennifer Wessel, Tanya M. Teslovich, Lizz Caulkins, Ryan Koesterer, Francisco Barajas-Olmos, Thomas W. Blackwell, Eric Boerwinkle, Jennifer A. Brody, Federico Centeno-Cruz, Ling Chen, Siying Chen, Cecilia Contreras-Cubas, Emilio Córdova, Adolfo Correa, Maria Cortes, Ralph A. De. Fronzo, Lawrence Dolan, Kimberly L. Drews, Amanda Elliott, James S. Floyd, Stacey Gabriel, Maria Eugenia Garay-Sevilla, Humberto García-Ortiz, Myron Gross, Sohee Han, Nancy L. Heard-Costa, Anne U. Jackson, Marit E. Jørgensen, Hyun Min Kang, Megan Kelsey, Bong-Jo Kim, Heikki A. Koistinen, Johanna Kuusisto, Joseph B. Leader, Allan Linneberg, Ching-Ti Liu, Jianjun Liu, Valeriya Lyssenko, Alisa K. Manning, Anthony Marcketta, Juan Manuel Malacara-Hernandez, Angélica Martínez-Hernández, Karen Matsuo, Elizabeth Mayer-Davis, Elvia Mendoza-Caamal, Karen L. Mohlke, Alanna C. Morrison, Anne Ndungu, Maggie C. Y. Ng, Colm O’Dushlaine, Anthony J. Payne, Catherine Pihoker, Broad Genomics Platform, Wendy S. Post, Michael Preuss, Bruce M. Psaty, Ramachandran S. Vasan, N. William Rayner, Alexander P. Reiner, Cristina Revilla-Monsalve, Neil R. Robertson, Nicola Santoro, Claudia Schurmann, Wing Yee So, Xavier Soberón, Heather M. Stringham, Tim M. Strom, Claudia H. T. Tam, Farook Thameem, Brian Tomlinson, Jason M. Torres, Russell P. Tracy, Rob M. van Dam, Marijana Vujkovic, Shuai Wang, Ryan P. Welch, Daniel R. Witte, Tien-Yin Wong, Gil Atzmon, Nir Barzilai, John Blangero, Lori L. Bonnycastle, Donald W. Bowden, John C. Chambers, Edmund Chan, Ching-Yu Cheng, Yoon Shin Cho, Francis S. Collins, Paul S. de Vries, Ravindranath Duggirala, Benjamin Glaser, Clicerio Gonzalez, Ma Elena Gonzalez, Leif Groop, Jaspal Singh Kooner, Soo Heon Kwak, Markku Laakso, Donna M. Lehman, Peter Nilsson, Timothy D. Spector, E. Shyong Tai, Tiinamaija Tuomi, Jaakko Tuomilehto, James G. Wilson, Carlos A. Aguilar-Salinas, Erwin Bottinger, Brian Burke, David J. Carey, Juliana C. N. Chan, Josée Dupuis, Philippe Frossard, Susan R. Heckbert, Mi Yeong Hwang, Young Jin Kim, H. Lester Kirchner, Jong-Young Lee, Juyoung Lee, Ruth J. F. Loos, Ronald C. W. Ma, Andrew D. Morris, Christopher J. O’Donnell, Colin N. A. Palmer, James Pankow, Kyong Soo Park, Asif Rasheed, Danish Saleheen, Xueling Sim, Kerrin S. Small, Yik Ying Teo, Christopher Haiman, Craig L. Hanis, Brian E. Henderson, Lorena Orozco, Teresa Tusié-Luna, Frederick E. Dewey, Aris Baras, Christian Gieger, Thomas Meitinger, Konstantin Strauch, Leslie Lange, Niels Grarup, Torben Hansen, Oluf Pedersen, Philip Zeitler, Dana Dabelea, Goncalo Abecasis, Graeme I. Bell, Nancy J. Cox, Mark Seielstad, Rob Sladek, James B. Meigs, Steve S. Rich, Jerome I. Rotter, Discov. EHR Collaboration, CHARGE, Lu. Camp, Pro. Di. GY, Go. T 2 D, ESP, SIGMA-T 2 D, T 2 D-GENES, AMP-T 2 D-GENES, David Altshuler, Noël P. Burtt, Laura J. Scott, Andrew P. Morris, Jose C. Florez, Mark I. Mc. Carthy & Michael Boehnke

Aims/Hypothesis: Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exomesequencing analyses of 20, 791 individuals with type 2 diabetes (T 2 D) and 24, 440 non-diabetic control participants from 5 ancestries.

Subgroup Ancestry Consortium Study Wake Forest African-American T 2 D-GENES Wake Forest School of Medicine Study JHS African-American T 2 D-GENES Jackson Heart Study Bio. Me African-American T 2 D-GENES Bio. Me Biobank Program (Bio. Me) ESP African-American & European ESP Exome Sequencing Project (ESP) Singapore East-Asian T 2 D-GENES Singapore Diabetes Cohort Study and Singapore Prospective Study Program KARE East-Asian T 2 D-GENES Korea Association Research Project SNUH East-Asian T 2 D-GENES Korea SNUH Hong Kong East-Asian T 2 D-GENES Research Studies in Hong Kong Go. T 2 D European Go. T 2 D Finland-United States Investigation of NIDDM Genetics (FUSION) Study Go. T 2 D European Go. T 2 D Malmo-Botnia Study Go. T 2 D European Go. T 2 D UKT 2 D Consortium Go. T 2 D European Go. T 2 D KORA METSIM European T 2 D-GENES Metabolic Syndrome in Men Study Ashkenazi European T 2 D-GENES Lu. CAMP European Lu. CAMP Go. DARTS European T 2 D-GENES Ashkenazi Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention, and Care Genetics of Diabetes and Audit Research Tayside Study FHS European T 2 D-GENES Framingham Heart Study SIGMA Latino SIGMA T 2 D Mexico City Diabetes Study SIGMA Latino SIGMA T 2 D Multiethnic Cohort SIGMA Latino SIGMA T 2 D Diabetes in Mexico Study SIGMA Latino SIGMA T 2 D UNAM/INCMNSZ Diabetes Study Starr County Hispanic San Antonio Hispanic Singapore South Asian T 2 D-GENES & SIGMA T 2 D Starr County, Texas San Antonio Mexican American Family Studies: San Antonio Family Heart Study, San Antonio Family Diabetes/Gallbladder Study, Veterans T 2 D-GENES Administration Genetic Epidemiology Study, and Family Investigation of Nephropathy and Diabetes Study - San Antonio Component T 2 D-GENES Singapore Indian Eye Study LOLIPOP South Asian T 2 D-GENES London Life Sciences Population Study PGR South Asian T 2 D-GENES Pakistan Genomic Resource Pro. DIGY Multi-ethnic Pro. DIGY Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Pro. DIGY Multi-ethnic Pro. DIGY SEARCH for Diabetes in Youth (SEARCH)

Genetic discovery from association analysis MC 4 R, PAM and SLC 30 A 8 These 15 associations are a substantial increase over the single association that was reported in a previous T 2 Dexome sequencing study and illustrate again the value of multi-ancestry association analyses—as only 9 out of 15 variants achieved P < 0. 05 in European samples. However, only two variants were not previously reported by GWAS: a variant in SFI 1 (rs 145181683, Arg 724 Trp; Supplementary Fig. 4) that failed to replicate in an independent cohort (n = 4, 522, P = 0. 90; Methods) and a low-frequency (in Hispanic/Latino individuals; MAF = 0. 89%) moderate-effect (odds ratio = 2. 17, 95% confidence interval = 1. 63– 2. 89) MC 4 R variant (rs 79783591, Ile 269 Asn) that has previously been shown to decrease MC 4 R activity and to be associated with obesity and T 2 D in smaller studies. Conditioning on body-mass index reduced but did not eliminate the MC 4 R Ile 269 Asn T 2 D association (P = 1. 0 × 10− 5).

Further insights from gene-level analyses Even if a gene-level association does not achieve exome-wide significance, it might still be of use to prioritize a gene as relevant to T 2 D 8 or predict whether loss or gain of protein function increases disease risk 7. To investigate potential insights that could be obtained by sub-exome-wide significant gene-level associations, we analysed 16 gene sets that were connected to T 2 D based on a variety of sources of evidence Seven out of eight T 2 D drug targets showed concordance between genetic and therapeutic directions of effect (three out of four inhibitor targets had an odds ratio < 1, four out of four agonist targets had an odds ratio > 1; one-sided binomial P = 0. 035; Fig. 2 f). The only exception was KCNJ 11 (odds ratio = 1. 59, inhibited by sulfonylureas), for which the gene-level signal was driven by a known 25 activating missense mutation (His 172 Arg); an analysis without this variant predicted the correct (odds ratio < 1) directional relationship. This finding is consistent with the known reciprocal roles of KCNJ 11 in both diabetes and persistent hyperinsulinaemic hypoglycaemia of

Comparison of rare and common variant associations Out of 10 exome-wide significant nonsynonymous single-variant associations from the sequence analysis, 8 were detected in the imputed GWAS analysis (PAX 4 Arg 192 His and MC 4 R Ile 269 Asn were not imputable), together with genome-wide significant non-coding variant associations in 14 additional loci

Inferences from nominally significant associations http: //www. type 2 diabetesgenetics. org/

Results: We identify gene-level associations of rare variants (with minor allele frequencies of less than 0. 5%) in 4 genes at exome-wide significance, including a series of more than 30 SLC 30 A 8 alleles that conveys protection against T 2 D, and in 12 gene sets, including those corresponding to T 2 D drug targets (P = 6. 1 × 10− 3) and candidate genes from knockout mice (P = 5. 2 × 10− 3). Within our study, the strongest T 2 D gene-level signals for rare variants explain at most 25% of the heritability of the strongest common single-variant signals, and the gene-level effect sizes of the rare variants that we observed in established T 2 D drug targets will require 75, 000– 185, 000 sequenced cases to achieve exome-wide significance.

Conclusions: We propose a method to interpret these modest rare-variant associations and to incorporate these associations into future target or gene prioritization efforts.

2013年 11月14日 Journal Club

May 30, 2012 米ニューヨーク市のマイケル ブルームバーグ市長は、肥満 対策に取り組むために、レストラン、映画館、食料品店での 高カロリーの清涼飲料の販売を規制するプランを発表した。 September 13, 2012 The New York City Board of Health approved a measure that says sugary beverages with more than 25 calories per eight ounces can only be sold in portions of 16 ounces or less. The ban on larger quantities applies to the following food service establishments: restaurants, mobile food carts, delis and concessions at movie theaters, stadiums and arenas. The new regulation, which goes into effect on March 12, 2013, will give establishments six months to comply.

https: //www. usatoday. com/story/news/nationnow/2014/11/05/berkeley-passes-soda-tax/18521923/ Berkeley, Calif. , became the first U. S. city to pass a law taxing sugary drinks including sodas. More than three-quarters of the votes cast were in favor of Measure D, according to the Alameda County Registrar of Voters. The measure will place a 1 -cent-an-ounce tax on soft drinks. It only needed a majority of "yes" votes to pass. In nearby San Francisco, city voters rejected a similar measure to tax sugary drinks. The measure needed two-thirds of the vote to approve the two-cent tax. Proponents of the Berkeley tax say the fee will help curb consumption of sodas, energy drinks and sweetened iced teas, beverages they say are contributing to the nation's obesity epidemic. That argument echoes calls made by other cities that have also tried to pass soda taxes but have failed in the face of well-funded opposition from soda manufacturers. Notably, former New York Mayor Michael Bloomberg's attempted ban on large-size sugary beverages was blocked by a New York state judge. Berkeley, which makes flouting the national norm a point of pride, managed to override its own sodabacked opposition. "Berkeley has a proud history of setting nationwide trends, such as non-smoking sections in restaurants and bars, curb cuts for wheelchairs, curbside recycling and public school food policies, " said Vicki Alexander, co-chair of the group campaigning to pass Measure D, in a statement announcing a victory for the campaign. The win may make it a leader, or just simply an outlier. Roger Salazar, a representative of the $10 million opposition campaign in Berkeley and San Francisco that was funded by soft-drink manufacturers, said the Berkeley vote meant little nationally. "Berkeley is very eclectic. It doesn't look like Anytown USA, " he told the Associated Press.

Christina A. Roberto, Ph. D 1; Hannah G. Lawman, Ph. D 2; Michael T. Le. Vasseur, Ph. D, MPH 1; Nandita Mitra, Ph. D 3; Ana Peterhans, MPH 1; Bradley Herring, Ph. D 4; Sara N. Bleich, Ph. D 5 1 Department of Medical Ethics and Health Policy, University of Pennsylvania Perelman School of Medicine, Philadelphia 2 Division of Chronic Disease Prevention, Philadelphia Department of Public Health, Philadelphia, Pennsylvania 3 Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia 4 Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 5 Department of Health Policy and Management, Harvard T. H. Chan School of Public Health, Boston, Massachusetts JAMA. 2019 May 14; 321(18): 1799 -1810. doi: 10. 1001/jama. 2019. 4249.

Importance Policy makers have implemented beverage taxes to generate revenue and reduce consumption of sweetened drinks. In January 2017, Philadelphia, Pennsylvania, became the second US city to implement a beverage excise tax (1. 5 cents per ounce). Objectives To compare changes in beverage prices and sales following the implementation of the tax in Philadelphia compared with Baltimore, Maryland (a control city without a tax) and to assess potential cross-border shopping to avoid the tax in neighboring zip codes.

Design, Setting, and Participants This study used a difference-in-differences approach and analyzed sales data to compare changes between January 1, 2016, before the tax, and December 31, 2017, after the tax. Differences by store type, beverage sweetener status, and beverage size were examined. The commercial retailer sales data included large chain store sales in Philadelphia, Baltimore, and the Pennsylvania zip codes bordering Philadelphia. These data reflect approximately 25% of the ounces of taxed beverages sold in Philadelphia. Exposures Philadelphia’s tax on sugar-sweetened and artificially sweetened beverages. Main Outcomes and Measures Change in taxed beverage prices and volume sales.

Seven US cities have implemented beverage excise taxes, where the tax is levied on the distribution of beverages and may only be partially passed through to consumers. Philadelphia implemented an excise tax of 1. 5 cents per ounce on the distribution of sugarsweetened and artificially sweetened drinks on January 1, 2017. As of mid 2019, seven U. S. cities and 39 countries around the world have implemented sugar-sweetened beverage taxes, mostly in the past few years (GFRP https: //benlockwood. com/papers/Allcott_Lockwood_Taubinsky_Soda. Taxes. JEP. pdf 2019) 1 ounce (oz) = 28. 3495 g 米液量オンスは 231/128立方インチ = 正確に 1. 804 6875立方インチであり[2]、正 確に 29. 573 529 5625ミリリットルである。ただし、栄養表示に使用する場合は、1 液量オンスは正確に 30ミリリットルとすることが法律(21 CFR 101. 9(b)(5)(viii))で定 められている。1米液量オンスの水の質量は約1. 04常用オンスである。

12 fl oz (360 m. L)

The data only included beverages sold at chain retailers (reflecting approximately one-quarter of taxed beverage ounces sold in Philadelphia). Analogous large-scale transaction data do not exist for smaller stores and restaurants.

Results A total of 291 stores (54 supermarkets, 20 mass merchandise stores, 217 pharmacies) were analyzed. The mean price per ounce of taxed beverages in Philadelphia increased from 5. 43 cents in 2016 to 6. 24 cents in 2017 at supermarkets; from 5. 28 cents to 6. 24 cents at mass merchandise stores, and from 6. 60 cents to 8. 28 cents at pharmacies. The mean price per ounce in Baltimore increased from 5. 33 cents in 2016 to 5. 50 cents in 2017 at supermarkets, from 6. 34 cents to 6. 52 cents at mass merchandise stores, and from 6. 76 cents to 6. 93 cents at pharmacies. The mean per-ounce difference in price between the 2 cities was 0. 65 cents (95% CI, 0. 60 cents-0. 69 cents; P<. 001) at supermarkets; 0. 87 cents (95 % CI, 0. 72 cents-1. 02 cents; P<. 001) at mass merchandise stores, and 1. 56 cents (95% CI, 1. 50 cents-1. 62 cents; P<. 001) at pharmacies. Total volume sales of taxed beverages in Philadelphia decreased by 1. 3 billion ounces (from 2. 475 billion to 1. 214 billion) or by 51. 0% after tax implementation. Volume sales in the Pennsylvania border zip codes, however, increased by 308. 2 million ounces (from 713. 1 million to 1. 021 billion), offsetting the decrease in Philadelphia's volume sales by 24. 4%. In Philadelphia, beverage volume sales in ounces per 4 -week period between before and after tax periods decreased from 4. 85 million to 1. 99 million at supermarkets, from 2. 98 million to 1. 72 million at mass merchandise stores, and from 0. 16 million to 0. 13 million at pharmacies. In Baltimore, the beverage volume sales in ounces decreased from 2. 83 million to 2. 81 million at supermarkets, from 1. 05 million to 1. 00 million at mass merchandise stores, and from 0. 14 million to 0. 13 million at pharmacies. This was a 58. 7% reduction at supermarkets (difference-in-differences, − 2. 85 million ounces; 95% CI, − 4. 10 million to − 1. 60 million ounces; P < . 001), 40. 4% reduction at mass merchandise stores (difference-in-differences, − 1. 20 million ounces; 95% CI, − 2. 04 million to − 0. 36 million ounces; P = . 001), and 12. 6% reduction in pharmacies (difference-in-differences, − 0. 02 million ounces; 95% CI, − 0. 03 million to − 0. 01 million ounces; P < . 001).

Conclusions and Relevance In Philadelphia in 2017, the implementation of a beverage excise tax on sugar-sweetened and artificially sweetened beverages was associated with significantly higher beverage prices and a significant and substantial decline in volume of taxed beverages sold. This decrease in taxed beverage sales volume was partially offset by increases in volume of sales in bordering areas.