@article {6582, title = {Genome-wide association analysis identifies six new loci associated with forced vital capacity.}, journal = {Nat Genet}, volume = {46}, year = {2014}, month = {2014 Jul}, pages = {669-77}, 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 {\texttimes} 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.

}, keywords = {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}, issn = {1546-1718}, doi = {10.1038/ng.3011}, author = {Loth, Daan W and Soler Artigas, Maria and Gharib, Sina A and Wain, Louise V and Franceschini, Nora and Koch, Beate and Pottinger, Tess D and Smith, Albert Vernon and Duan, Qing and Oldmeadow, Chris and Lee, Mi Kyeong and Strachan, David P and James, Alan L and Huffman, Jennifer E and Vitart, Veronique and Ramasamy, Adaikalavan and Wareham, Nicholas J and Kaprio, Jaakko and Wang, Xin-Qun and Trochet, Holly and K{\"a}h{\"o}nen, Mika and Flexeder, Claudia and Albrecht, Eva and Lopez, Lorna M and de Jong, Kim and Thyagarajan, Bharat and Alves, Alexessander Couto and Enroth, Stefan and Omenaas, Ernst and Joshi, Peter K and Fall, Tove and Vi{\~n}uela, Ana and Launer, Lenore J and Loehr, Laura R and Fornage, Myriam and Li, Guo and Wilk, Jemma B and Tang, Wenbo and Manichaikul, Ani and Lahousse, Lies and Harris, Tamara B and North, Kari E and Rudnicka, Alicja R and Hui, Jennie and Gu, Xiangjun and Lumley, Thomas and Wright, Alan F and Hastie, Nicholas D and Campbell, Susan and Kumar, Rajesh and Pin, Isabelle and Scott, Robert A and Pietil{\"a}inen, Kirsi H and Surakka, Ida and Liu, Yongmei and Holliday, Elizabeth G and Schulz, Holger and Heinrich, Joachim and Davies, Gail and Vonk, Judith M and Wojczynski, Mary and Pouta, Anneli and Johansson, Asa and Wild, Sarah H and Ingelsson, Erik and Rivadeneira, Fernando and V{\"o}lzke, Henry and Hysi, Pirro G and Eiriksdottir, Gudny and Morrison, Alanna C and Rotter, Jerome I and Gao, Wei and Postma, Dirkje S and White, Wendy B and Rich, Stephen S and Hofman, Albert and Aspelund, Thor and Couper, David and Smith, Lewis J and Psaty, Bruce M and Lohman, Kurt and Burchard, Esteban G and Uitterlinden, Andr{\'e} G and Garcia, Melissa and Joubert, Bonnie R and McArdle, Wendy L and Musk, A Bill and Hansel, Nadia and Heckbert, Susan R and Zgaga, Lina and van Meurs, Joyce B J and Navarro, Pau and Rudan, Igor and Oh, Yeon-Mok and Redline, Susan and Jarvis, Deborah L and Zhao, Jing Hua and Rantanen, Taina and O{\textquoteright}Connor, George T and Ripatti, Samuli and Scott, Rodney J and Karrasch, Stefan and Grallert, Harald and Gaddis, Nathan C and Starr, John M and Wijmenga, Cisca and Minster, Ryan L and Lederer, David J and Pekkanen, Juha and Gyllensten, Ulf and Campbell, Harry and Morris, Andrew P and Gl{\"a}ser, Sven and Hammond, Christopher J and Burkart, Kristin M and Beilby, John and Kritchevsky, Stephen B and Gudnason, Vilmundur and Hancock, Dana B and Williams, O Dale and Polasek, Ozren and Zemunik, Tatijana and Kolcic, Ivana and Petrini, Marcy F and Wjst, Matthias and Kim, Woo Jin and Porteous, David J and Scotland, Generation and Smith, Blair H and Viljanen, Anne and Heli{\"o}vaara, Markku and Attia, John R and Sayers, Ian and Hampel, Regina and Gieger, Christian and Deary, Ian J and Boezen, H Marike and Newman, Anne and Jarvelin, Marjo-Riitta and Wilson, James F and Lind, Lars and Stricker, Bruno H and Teumer, Alexander and Spector, Timothy D and Mel{\'e}n, Erik and Peters, Marjolein J and Lange, Leslie A and Barr, R Graham and Bracke, Ken R and Verhamme, Fien M and Sung, Joohon and Hiemstra, Pieter S and Cassano, Patricia A and Sood, Akshay and Hayward, Caroline and Dupuis, Jos{\'e}e and Hall, Ian P and Brusselle, Guy G and Tobin, Martin D and London, Stephanie J} } @article {6594, title = {Telomere length and the risk of atrial fibrillation: insights into the role of biological versus chronological aging.}, journal = {Circ Arrhythm Electrophysiol}, volume = {7}, year = {2014}, month = {2014 Dec}, pages = {1026-32}, abstract = {

BACKGROUND: Advanced age is the most important risk factor for atrial fibrillation (AF); however, the mechanism remains unknown. Telomeres, regions of DNA that shorten with cell division, are considered reliable markers of biological aging. We sought to examine the association between leukocyte telomere length (LTL) and incident AF in a large population-based cohort using direct LTL measurements and genetic data. To further explore our findings, we compared atrial cell telomere length and LTL in cardiac surgery patients.

METHODS AND RESULTS: Mean LTL and the TERT rs2736100 single nucleotide polymorphism were assessed as predictors of incident AF in the Cardiovascular Health Study (CHS). Among the surgical patients, within subject comparison of atrial cell telomere length versus LTL was assessed. Among 1639 CHS participants, we observed no relationship between mean LTL and incident AF before and after adjustment for potential confounders (adjusted hazard ratio, 1.09; 95\% confidence interval: 0.92-1.29; P=0.299); chronologic age remained strongly associated with AF in the same model. No association was observed between the TERT rs2736100 single nucleotide polymorphism and incident AF (adjusted hazard ratio: 0.95; 95\% confidence interval: 0.88-1.04; P=0.265). In 35 cardiac surgery patients (26 with AF), atrial cell telomere length was longer than LTL (1.19 {\textpm} 0.20 versus 1.02 {\textpm} 0.25 [T/S ratio], P<0.001), a finding that remained consistent within the AF subgroup.

CONCLUSIONS: Our study revealed no evidence of an association between LTL and incident AF and no evidence of relative atrial cell telomere shortening in AF. Chronological aging independent of biological markers of aging is the primary risk factor for AF.

}, keywords = {Age Factors, Aged, Aging, Atrial Fibrillation, California, Cardiac Surgical Procedures, Cellular Senescence, Cross-Sectional Studies, Female, Genetic Predisposition to Disease, Humans, Incidence, Leukocytes, Male, Phenotype, Polymorphism, Single Nucleotide, Prospective Studies, Risk Assessment, Risk Factors, Telomerase, Telomere, Time Factors}, issn = {1941-3084}, doi = {10.1161/CIRCEP.114.001781}, author = {Roberts, Jason D and Dewland, Thomas A and Longoria, James and Fitzpatrick, Annette L and Ziv, Elad and Hu, Donglei and Lin, Jue and Glidden, David V and Psaty, Bruce M and Burchard, Esteban G and Blackburn, Elizabeth H and Olgin, Jeffrey E and Heckbert, Susan R and Marcus, Gregory M} } @article {7165, title = {Genetic Investigation Into the Differential Risk of Atrial Fibrillation Among Black and White Individuals.}, journal = {JAMA Cardiol}, volume = {1}, year = {2016}, month = {2016 Jul 1}, pages = {442-50}, abstract = {

IMPORTANCE: White persons have a higher risk of atrial fibrillation (AF) compared with black individuals despite a lower prevalence of risk factors. This difference may be due, at least in part, to genetic factors.

OBJECTIVES: To determine whether 9 single-nucleotide polymorphisms (SNPs) associated with AF account for this paradoxical differential racial risk for AF and to use admixture mapping to search genome-wide for loci that may account for this phenomenon.

DESIGN, SETTING, AND PARTICIPANTS: Genome-wide admixture analysis and candidate SNP study involving 3 population-based cohort studies that were initiated between 1987 and 1997, including the Cardiovascular Health Study (CHS) (n = 4173), the Atherosclerosis Risk in Communities (ARIC) (n = 12 341) study, and the Health, Aging, and Body Composition (Health ABC) (n = 1015) study. In all 3 studies, race was self-identified. Cox proportional hazards regression models and the proportion of treatment effect method were used to determine the impact of 9 AF-risk SNPs among participants from CHS and the ARIC study. The present study began July 1, 2012, and was completed in 2015.

MAIN OUTCOMES AND MEASURES: Incident AF systematically ascertained using clinic visit electrocardiograms, hospital discharge diagnosis codes, death certificates, and Medicare claims data.

RESULTS: A single SNP, rs10824026 (chromosome 10: position 73661450), was found to significantly mediate the higher risk for AF in white participants compared with black participants in CHS (11.4\%; 95\% CI, 2.9\%-29.9\%) and ARIC (31.7\%; 95\% CI, 16.0\%-53.0\%). Admixture mapping was performed in a meta-analysis of black participants within CHS (n = 811), ARIC (n = 3112), and Health ABC (n = 1015). No loci that reached the prespecified statistical threshold for genome-wide significance were identified.

CONCLUSIONS AND RELEVANCE: The rs10824026 SNP on chromosome 10q22 mediates a modest proportion of the increased risk of AF among white individuals compared with black individuals, potentially through an effect on gene expression levels of MYOZ1. No additional genetic variants accounting for a significant portion of the differential racial risk of AF were identified with genome-wide admixture mapping, suggesting that additional genetic or environmental influences beyond single SNPs in isolation may account for the paradoxical racial risk of AF among white individuals and black individuals.

}, issn = {2380-6591}, doi = {10.1001/jamacardio.2016.1185}, author = {Roberts, Jason D and Hu, Donglei and Heckbert, Susan R and Alonso, Alvaro and Dewland, Thomas A and Vittinghoff, Eric and Liu, Yongmei and Psaty, Bruce M and Olgin, Jeffrey E and Magnani, Jared W and Huntsman, Scott and Burchard, Esteban G and Arking, Dan E and Bibbins-Domingo, Kirsten and Harris, Tamara B and Perez, Marco V and Ziv, Elad and Marcus, Gregory M} } @article {7819, title = {Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function.}, journal = {Nat Commun}, volume = {9}, year = {2018}, month = {2018 Jul 30}, pages = {2976}, abstract = {

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci.

}, issn = {2041-1723}, doi = {10.1038/s41467-018-05369-0}, author = {Wyss, Annah B and Sofer, Tamar and Lee, Mi Kyeong and Terzikhan, Natalie and Nguyen, Jennifer N and Lahousse, Lies and Latourelle, Jeanne C and Smith, Albert Vernon and Bartz, Traci M and Feitosa, Mary F and Gao, Wei and Ahluwalia, Tarunveer S and Tang, Wenbo and Oldmeadow, Christopher and Duan, Qing and de Jong, Kim and Wojczynski, Mary K and Wang, Xin-Qun and Noordam, Raymond and Hartwig, Fernando Pires and Jackson, Victoria E and Wang, Tianyuan and Obeidat, Ma{\textquoteright}en and Hobbs, Brian D and Huan, Tianxiao and Gui, Hongsheng and Parker, Margaret M and Hu, Donglei and Mogil, Lauren S and Kichaev, Gleb and Jin, Jianping and Graff, Mariaelisa and Harris, Tamara B and Kalhan, Ravi and Heckbert, Susan R and Paternoster, Lavinia and Burkart, Kristin M and Liu, Yongmei and Holliday, Elizabeth G and Wilson, James G and Vonk, Judith M and Sanders, Jason L and Barr, R Graham and de Mutsert, Ren{\'e}e and Menezes, Ana Maria Baptista and Adams, Hieab H H and van den Berge, Maarten and Joehanes, Roby and Levin, Albert M and Liberto, Jennifer and Launer, Lenore J and Morrison, Alanna C and Sitlani, Colleen M and Celed{\'o}n, Juan C and Kritchevsky, Stephen B and Scott, Rodney J and Christensen, Kaare and Rotter, Jerome I and Bonten, Tobias N and Wehrmeister, Fernando C{\'e}sar and Boss{\'e}, Yohan and Xiao, Shujie and Oh, Sam and Franceschini, Nora and Brody, Jennifer A and Kaplan, Robert C and Lohman, Kurt and McEvoy, Mark and Province, Michael A and Rosendaal, Frits R and Taylor, Kent D and Nickle, David C and Williams, L Keoki and Burchard, Esteban G and Wheeler, Heather E and Sin, Don D and Gudnason, Vilmundur and North, Kari E and Fornage, Myriam and Psaty, Bruce M and Myers, Richard H and O{\textquoteright}Connor, George and Hansen, Torben and Laurie, Cathy C and Cassano, Patricia A and Sung, Joohon and Kim, Woo Jin and Attia, John R and Lange, Leslie and Boezen, H Marike and Thyagarajan, Bharat and Rich, Stephen S and Mook-Kanamori, Dennis O and Horta, Bernardo Lessa and Uitterlinden, Andr{\'e} G and Im, Hae Kyung and Cho, Michael H and Brusselle, Guy G and Gharib, Sina A and Dupuis, Jos{\'e}e and Manichaikul, Ani and London, Stephanie J} } @article {8621, title = {Inherited causes of clonal haematopoiesis in 97,691 whole genomes.}, journal = {Nature}, volume = {586}, year = {2020}, month = {2020 10}, pages = {763-768}, abstract = {

Age is the dominant risk factor for most chronic human diseases, but the mechanisms through which ageing confers this risk are largely unknown. The age-related acquisition of somatic mutations that lead to clonal expansion in regenerating haematopoietic stem cell populations has recently been associated with both haematological cancer and coronary heart disease-this phenomenon is~termed clonal haematopoiesis of indeterminate potential (CHIP). Simultaneous analyses of germline and somatic whole-genome sequences provide the opportunity to identify root causes of CHIP. Here we analyse high-coverage whole-genome sequences from 97,691 participants of diverse ancestries in the National Heart, Lung, and Blood Institute Trans-omics for Precision Medicine (TOPMed) programme, and identify 4,229 individuals with CHIP. We identify associations with blood cell, lipid and inflammatory traits that are specific to different CHIP~driver genes. Association of a genome-wide set of germline genetic variants enabled the identification of three genetic loci associated with CHIP status, including one locus at TET2 that was specific to individuals of African ancestry. In silico-informed in vitro evaluation of the TET2 germline locus enabled the identification of a causal variant that disrupts a TET2 distal enhancer, resulting in increased self-renewal of haematopoietic stem cells. Overall, we observe that germline genetic variation shapes haematopoietic stem cell function, leading to CHIP through mechanisms that are specific to clonal haematopoiesis as well as shared mechanisms that lead to somatic mutations across tissues.

}, issn = {1476-4687}, doi = {10.1038/s41586-020-2819-2}, author = {Bick, Alexander G and Weinstock, Joshua S and Nandakumar, Satish K and Fulco, Charles P and Bao, Erik L and Zekavat, Seyedeh M and Szeto, Mindy D and Liao, Xiaotian and Leventhal, Matthew J and Nasser, Joseph and Chang, Kyle and Laurie, Cecelia and Burugula, Bala Bharathi and Gibson, Christopher J and Lin, Amy E and Taub, Margaret A and Aguet, Francois and Ardlie, Kristin and Mitchell, Braxton D and Barnes, Kathleen C and Moscati, Arden and Fornage, Myriam and Redline, Susan and Psaty, Bruce M and Silverman, Edwin K and Weiss, Scott T and Palmer, Nicholette D and Vasan, Ramachandran S and Burchard, Esteban G and Kardia, Sharon L R and He, Jiang and Kaplan, Robert C and Smith, Nicholas L and Arnett, Donna K and Schwartz, David A and Correa, Adolfo and de Andrade, Mariza and Guo, Xiuqing and Konkle, Barbara A and Custer, Brian and Peralta, Juan M and Gui, Hongsheng and Meyers, Deborah A and McGarvey, Stephen T and Chen, Ida Yii-Der and Shoemaker, M Benjamin and Peyser, Patricia A and Broome, Jai G and Gogarten, Stephanie M and Wang, Fei Fei and Wong, Quenna and Montasser, May E and Daya, Michelle and Kenny, Eimear E and North, Kari E and Launer, Lenore J and Cade, Brian E and Bis, Joshua C and Cho, Michael H and Lasky-Su, Jessica and Bowden, Donald W and Cupples, L Adrienne and Mak, Angel C Y and Becker, Lewis C and Smith, Jennifer A and Kelly, Tanika N and Aslibekyan, Stella and Heckbert, Susan R and Tiwari, Hemant K and Yang, Ivana V and Heit, John A and Lubitz, Steven A and Johnsen, Jill M and Curran, Joanne E and Wenzel, Sally E and Weeks, Daniel E and Rao, Dabeeru C and Darbar, Dawood and Moon, Jee-Young and Tracy, Russell P and Buth, Erin J and Rafaels, Nicholas and Loos, Ruth J F and Durda, Peter and Liu, Yongmei and Hou, Lifang and Lee, Jiwon and Kachroo, Priyadarshini and Freedman, Barry I and Levy, Daniel and Bielak, Lawrence F and Hixson, James E and Floyd, James S and Whitsel, Eric A and Ellinor, Patrick T and Irvin, Marguerite R and Fingerlin, Tasha E and Raffield, Laura M and Armasu, Sebastian M and Wheeler, Marsha M and Sabino, Ester C and Blangero, John and Williams, L Keoki and Levy, Bruce D and Sheu, Wayne Huey-Herng and Roden, Dan M and Boerwinkle, Eric and Manson, JoAnn E and Mathias, Rasika A and Desai, Pinkal and Taylor, Kent D and Johnson, Andrew D and Auer, Paul L and Kooperberg, Charles and Laurie, Cathy C and Blackwell, Thomas W and Smith, Albert V and Zhao, Hongyu and Lange, Ethan and Lange, Leslie and Rich, Stephen S and Rotter, Jerome I and Wilson, James G and Scheet, Paul and Kitzman, Jacob O and Lander, Eric S and Engreitz, Jesse M and Ebert, Benjamin L and Reiner, Alexander P and Jaiswal, Siddhartha and Abecasis, Goncalo and Sankaran, Vijay G and Kathiresan, Sekar and Natarajan, Pradeep} } @article {8666, title = {Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program.}, journal = {Nature}, volume = {590}, year = {2021}, month = {2021 02}, pages = {290-299}, abstract = {

The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data. The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes). In the first 53,831 TOPMed samples, we detected more than 400~million single-nucleotide and insertion or deletion variants after alignment with the reference genome. Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci. Among the more than 400~million detected variants, 97\% have frequencies of less than 1\% and 46\% are singletons that are present in only one individual (53\% among unrelated individuals). These rare variants provide insights into mutational processes and recent human evolutionary history. The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 0.01\%.

}, issn = {1476-4687}, doi = {10.1038/s41586-021-03205-y}, author = {Taliun, Daniel and Harris, Daniel N and Kessler, Michael D and Carlson, Jedidiah and Szpiech, Zachary A and Torres, Raul and Taliun, Sarah A Gagliano and Corvelo, Andr{\'e} and Gogarten, Stephanie M and Kang, Hyun Min and Pitsillides, Achilleas N and LeFaive, Jonathon and Lee, Seung-Been and Tian, Xiaowen and Browning, Brian L and Das, Sayantan and Emde, Anne-Katrin and Clarke, Wayne E and Loesch, Douglas P and Shetty, Amol C and Blackwell, Thomas W and Smith, Albert V and Wong, Quenna and Liu, Xiaoming and Conomos, Matthew P and Bobo, Dean M and Aguet, Francois and Albert, Christine and Alonso, Alvaro and Ardlie, Kristin G and Arking, Dan E and Aslibekyan, Stella and Auer, Paul L and Barnard, John and Barr, R Graham and Barwick, Lucas and Becker, Lewis C and Beer, Rebecca L and Benjamin, Emelia J and Bielak, Lawrence F and Blangero, John and Boehnke, Michael and Bowden, Donald W and Brody, Jennifer A and Burchard, Esteban G and Cade, Brian E and Casella, James F and Chalazan, Brandon and Chasman, Daniel I and Chen, Yii-Der Ida and Cho, Michael H and Choi, Seung Hoan and Chung, Mina K and Clish, Clary B and Correa, Adolfo and Curran, Joanne E and Custer, Brian and Darbar, Dawood and Daya, Michelle and de Andrade, Mariza and DeMeo, Dawn L and Dutcher, Susan K and Ellinor, Patrick T and Emery, Leslie S and Eng, Celeste and Fatkin, Diane and Fingerlin, Tasha and Forer, Lukas and Fornage, Myriam and Franceschini, Nora and Fuchsberger, Christian and Fullerton, Stephanie M and Germer, Soren and Gladwin, Mark T and Gottlieb, Daniel J and Guo, Xiuqing and Hall, Michael E and He, Jiang and Heard-Costa, Nancy L and Heckbert, Susan R and Irvin, Marguerite R and Johnsen, Jill M and Johnson, Andrew D and Kaplan, Robert and Kardia, Sharon L R and Kelly, Tanika and Kelly, Shannon and Kenny, Eimear E and Kiel, Douglas P and Klemmer, Robert and Konkle, Barbara A and Kooperberg, Charles and K{\"o}ttgen, Anna and Lange, Leslie A and Lasky-Su, Jessica and Levy, Daniel and Lin, Xihong and Lin, Keng-Han and Liu, Chunyu and Loos, Ruth J F and Garman, Lori and Gerszten, Robert and Lubitz, Steven A and Lunetta, Kathryn L and Mak, Angel C Y and Manichaikul, Ani and Manning, Alisa K and Mathias, Rasika A and McManus, David D and McGarvey, Stephen T and Meigs, James B and Meyers, Deborah A and Mikulla, Julie L and Minear, Mollie A and Mitchell, Braxton D and Mohanty, Sanghamitra and Montasser, May E and Montgomery, Courtney and Morrison, Alanna C and Murabito, Joanne M and Natale, Andrea and Natarajan, Pradeep and Nelson, Sarah C and North, Kari E and O{\textquoteright}Connell, Jeffrey R and Palmer, Nicholette D and Pankratz, Nathan and Peloso, Gina M and Peyser, Patricia A and Pleiness, Jacob and Post, Wendy S and Psaty, Bruce M and Rao, D C and Redline, Susan and Reiner, Alexander P and Roden, Dan and Rotter, Jerome I and Ruczinski, Ingo and Sarnowski, Chloe and Schoenherr, Sebastian and Schwartz, David A and Seo, Jeong-Sun and Seshadri, Sudha and Sheehan, Vivien A and Sheu, Wayne H and Shoemaker, M Benjamin and Smith, Nicholas L and Smith, Jennifer A and Sotoodehnia, Nona and Stilp, Adrienne M and Tang, Weihong and Taylor, Kent D and Telen, Marilyn and Thornton, Timothy A and Tracy, Russell P and Van Den Berg, David J and Vasan, Ramachandran S and Viaud-Martinez, Karine A and Vrieze, Scott and Weeks, Daniel E and Weir, Bruce S and Weiss, Scott T and Weng, Lu-Chen and Willer, Cristen J and Zhang, Yingze and Zhao, Xutong and Arnett, Donna K and Ashley-Koch, Allison E and Barnes, Kathleen C and Boerwinkle, Eric and Gabriel, Stacey and Gibbs, Richard and Rice, Kenneth M and Rich, Stephen S and Silverman, Edwin K and Qasba, Pankaj and Gan, Weiniu and Papanicolaou, George J and Nickerson, Deborah A and Browning, Sharon R and Zody, Michael C and Z{\"o}llner, Sebastian and Wilson, James G and Cupples, L Adrienne and Laurie, Cathy C and Jaquish, Cashell E and Hernandez, Ryan D and O{\textquoteright}Connor, Timothy D and Abecasis, Goncalo R} } @article {9484, title = {WHOLE GENOME SEQUENCING ANALYSIS OF BODY MASS INDEX IDENTIFIES NOVEL AFRICAN ANCESTRY-SPECIFIC RISK ALLELE.}, journal = {medRxiv}, year = {2023}, month = {2023 Aug 22}, abstract = {

Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-genome sequencing (WGS) data from 88,873 participants from the Trans-Omics for Precision Medicine (TOPMed) Program, of which 51\% were of non-European population groups. We discovered 18 BMI-associated signals ( < 5 {\texttimes} 10 ). Notably, we identified and replicated a novel low frequency single nucleotide polymorphism (SNP) in that was common in individuals of African descent. Using a diverse study population, we further identified two novel secondary signals in known BMI loci and pinpointed two likely causal variants in the and loci. Our work demonstrates the benefits of combining WGS and diverse cohorts in expanding current catalog of variants and genes confer risk for obesity, bringing us one step closer to personalized medicine.

}, doi = {10.1101/2023.08.21.23293271}, author = {Zhang, Xinruo and Brody, Jennifer A and Graff, Mariaelisa and Highland, Heather M and Chami, Nathalie and Xu, Hanfei and Wang, Zhe and Ferrier, Kendra and Chittoor, Geetha and Josyula, Navya S and Li, Xihao and Li, Zilin and Allison, Matthew A and Becker, Diane M and Bielak, Lawrence F and Bis, Joshua C and Boorgula, Meher Preethi and Bowden, Donald W and Broome, Jai G and Buth, Erin J and Carlson, Christopher S and Chang, Kyong-Mi and Chavan, Sameer and Chiu, Yen-Feng and Chuang, Lee-Ming and Conomos, Matthew P and DeMeo, Dawn L and Du, Margaret and Duggirala, Ravindranath and Eng, Celeste and Fohner, Alison E and Freedman, Barry I and Garrett, Melanie E and Guo, Xiuqing and Haiman, Chris and Heavner, Benjamin D and Hidalgo, Bertha and Hixson, James E and Ho, Yuk-Lam and Hobbs, Brian D and Hu, Donglei and Hui, Qin and Hwu, Chii-Min and Jackson, Rebecca D and Jain, Deepti and Kalyani, Rita R and Kardia, Sharon L R and Kelly, Tanika N and Lange, Ethan M and LeNoir, Michael and Li, Changwei and Marchand, Loic Le and McDonald, Merry-Lynn N and McHugh, Caitlin P and Morrison, Alanna C and Naseri, Take and O{\textquoteright}Connell, Jeffrey and O{\textquoteright}Donnell, Christopher J and Palmer, Nicholette D and Pankow, James S and Perry, James A and Peters, Ulrike and Preuss, Michael H and Rao, D C and Regan, Elizabeth A and Reupena, Sefuiva M and Roden, Dan M and Rodriguez-Santana, Jose and Sitlani, Colleen M and Smith, Jennifer A and Tiwari, Hemant K and Vasan, Ramachandran S and Wang, Zeyuan and Weeks, Daniel E and Wessel, Jennifer and Wiggins, Kerri L and Wilkens, Lynne R and Wilson, Peter W F and Yanek, Lisa R and Yoneda, Zachary T and Zhao, Wei and Z{\"o}llner, Sebastian and Arnett, Donna K and Ashley-Koch, Allison E and Barnes, Kathleen C and Blangero, John and Boerwinkle, Eric and Burchard, Esteban G and Carson, April P and Chasman, Daniel I and Chen, Yii-Der Ida and Curran, Joanne E and Fornage, Myriam and Gordeuk, Victor R and He, Jiang and Heckbert, Susan R and Hou, Lifang and Irvin, Marguerite R and Kooperberg, Charles and Minster, Ryan L and Mitchell, Braxton D and Nouraie, Mehdi and Psaty, Bruce M and Raffield, Laura M and Reiner, Alexander P and Rich, Stephen S and Rotter, Jerome I and Shoemaker, M Benjamin and Smith, Nicholas L and Taylor, Kent D and Telen, Marilyn J and Weiss, Scott T and Zhang, Yingze and Costa, Nancy Heard- and Sun, Yan V and Lin, Xihong and Cupples, L Adrienne and Lange, Leslie A and Liu, Ching-Ti and Loos, Ruth J F and North, Kari E and Justice, Anne E} }