@article {1104, title = {Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity.}, journal = {Aging Cell}, volume = {8}, year = {2009}, month = {2009 Aug}, pages = {460-72}, abstract = {

The insulin/IGF1 signaling pathways affect lifespan in several model organisms, including worms, flies and mice. To investigate whether common genetic variation in this pathway influences lifespan in humans, we genotyped 291 common variants in 30 genes encoding proteins in the insulin/IGF1 signaling pathway in a cohort of elderly Caucasian women selected from the Study of Osteoporotic Fractures (SOF). The cohort included 293 long-lived cases (lifespan > or = 92 years (y), mean +/- standard deviation (SD) = 95.3 +/- 2.2y) and 603 average-lifespan controls (lifespan < or = 79y, mean = 75.7 +/- 2.6y). Variants were selected for genotyping using a haplotype-tagging approach. We found a modest excess of variants nominally associated with longevity. Nominally significant variants were then replicated in two additional Caucasian cohorts including both males and females: the Cardiovascular Health Study and Ashkenazi Jewish Centenarians. An intronic single nucleotide polymorphism in AKT1, rs3803304, was significantly associated with lifespan in a meta-analysis across the three cohorts (OR = 0.78 95\%CI = 0.68-0.89, adjusted P = 0.043); two intronic single nucleotide polymorphisms in FOXO3A demonstrated a significant lifespan association among women only (rs1935949, OR = 1.35, 95\%CI = 1.15-1.57, adjusted P = 0.0093). These results demonstrate that common variants in several genes in the insulin/IGF1 pathway are associated with human lifespan.

}, keywords = {Aged, Aged, 80 and over, Female, Follow-Up Studies, Forkhead Box Protein O3, Forkhead Transcription Factors, Genome, Human, Genotype, Humans, Insulin, Insulin-Like Growth Factor I, Longevity, Male, Osteoporosis, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins c-akt, Signal Transduction}, issn = {1474-9726}, doi = {10.1111/j.1474-9726.2009.00493.x}, author = {Pawlikowska, Ludmila and Hu, Donglei and Huntsman, Scott and Sung, Andrew and Chu, Catherine and Chen, Justin and Joyner, Alexander H and Schork, Nicholas J and Hsueh, Wen-Chi and Reiner, Alexander P and Psaty, Bruce M and Atzmon, Gil and Barzilai, Nir and Cummings, Steven R and Browner, Warren S and Kwok, Pui-Yan and Ziv, Elad} } @article {6179, title = {Impact of ancestry and common genetic variants on QT interval in African Americans.}, journal = {Circ Cardiovasc Genet}, volume = {5}, year = {2012}, month = {2012 Dec}, pages = {647-55}, abstract = {

BACKGROUND: Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death and low incidence of atrial fibrillation in individuals of African ancestry. We tested the hypotheses that African ancestry and common genetic variants are associated with prolonged duration of cardiac repolarization, a central pathophysiological determinant of arrhythmia, as measured by the electrocardiographic QT interval.

METHODS AND RESULTS: First, individual estimates of African and European ancestry were inferred from genome-wide single-nucleotide polymorphism (SNP) data in 7 population-based cohorts of African Americans (n=12,097) and regressed on measured QT interval from ECGs. Second, imputation was performed for 2.8 million SNPs, and a genome-wide association study of QT interval was performed in 10 cohorts (n=13,105). There was no evidence of association between genetic ancestry and QT interval (P=0.94). Genome-wide significant associations (P<2.5 {\texttimes} 10(-8)) were identified with SNPs at 2 loci, upstream of the genes NOS1AP (rs12143842, P=2 {\texttimes} 10(-15)) and ATP1B1 (rs1320976, P=2 {\texttimes} 10(-10)). The most significant SNP in NOS1AP was the same as the strongest SNP previously associated with QT interval in individuals of European ancestry. Low probability values (P<10(-5)) were observed for SNPs at several other loci previously identified in genome-wide association studies in individuals of European ancestry, including KCNQ1, KCNH2, LITAF, and PLN.

CONCLUSIONS: We observed no difference in duration of cardiac repolarization with global genetic indices of African American ancestry. In addition, our genome-wide association study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include individuals of African ancestry.

}, keywords = {Adult, African Americans, Aged, Electrocardiography, European Continental Ancestry Group, Female, Genealogy and Heraldry, Genetic Variation, Genome, Human, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide}, issn = {1942-3268}, doi = {10.1161/CIRCGENETICS.112.962787}, author = {Smith, J Gustav and Avery, Christy L and Evans, Daniel S and Nalls, Michael A and Meng, Yan A and Smith, Erin N and Palmer, Cameron and Tanaka, Toshiko and Mehra, Reena and Butler, Anne M and Young, Taylor and Buxbaum, Sarah G and Kerr, Kathleen F and Berenson, Gerald S and Schnabel, Renate B and Li, Guo and Ellinor, Patrick T and Magnani, Jared W and Chen, Wei and Bis, Joshua C and Curb, J David and Hsueh, Wen-Chi and Rotter, Jerome I and Liu, Yongmei and Newman, Anne B and Limacher, Marian C and North, Kari E and Reiner, Alexander P and Quibrera, P Miguel and Schork, Nicholas J and Singleton, Andrew B and Psaty, Bruce M and Soliman, Elsayed Z and Solomon, Allen J and Srinivasan, Sathanur R and Alonso, Alvaro and Wallace, Robert and Redline, Susan and Zhang, Zhu-Ming and Post, Wendy S and Zonderman, Alan B and Taylor, Herman A and Murray, Sarah S and Ferrucci, Luigi and Arking, Dan E and Evans, Michele K and Fox, Ervin R and Sotoodehnia, Nona and Heckbert, Susan R and Whitsel, Eric A and Newton-Cheh, Christopher} } @article {6084, title = {Novel loci associated with PR interval in a genome-wide association study of 10 African American cohorts.}, journal = {Circ Cardiovasc Genet}, volume = {5}, year = {2012}, month = {2012 Dec}, pages = {639-46}, abstract = {

BACKGROUND: The PR interval, as measured by the resting, standard 12-lead ECG, reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, including genome-wide association studies that have identified common genetic variants at 9 loci influencing PR in populations of European and Asian descent. However, few studies have examined loci associated with PR in African Americans.

METHODS AND RESULTS: We present results from the largest genome-wide association study to date of PR in 13 415 adults of African descent from 10 cohorts. We tested for association between PR (ms) and ≈2.8 million genotyped and imputed single-nucleotide polymorphisms. Imputation was performed using HapMap 2 YRI and CEU panels. Study-specific results, adjusted for global ancestry and clinical correlates of PR, were meta-analyzed using the inverse variance method. Variation in genome-wide test statistic distributions was noted within studies (λ range: 0.9-1.1), although not after genomic control correction was applied to the overall meta-analysis (λ: 1.008). In addition to generalizing previously reported associations with MEIS1, SCN5A, ARHGAP24, CAV1, and TBX5 to African American populations at the genome-wide significance level (P<5.0 {\texttimes} 10(-8)), we also identified a novel locus: ITGA9, located in a region previously implicated in SCN5A expression. The 3p21 region harboring SCN5A also contained 2 additional independent secondary signals influencing PR (P<5.0 {\texttimes} 10(-8)).

CONCLUSIONS: This study demonstrates the ability to map novel loci in African Americans as well as the generalizability of loci associated with PR across populations of African, European, and Asian descent.

}, keywords = {Adult, African Americans, Cohort Studies, Electrocardiography, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide}, issn = {1942-3268}, doi = {10.1161/CIRCGENETICS.112.963991}, author = {Butler, Anne M and Yin, Xiaoyan and Evans, Daniel S and Nalls, Michael A and Smith, Erin N and Tanaka, Toshiko and Li, Guo and Buxbaum, Sarah G and Whitsel, Eric A and Alonso, Alvaro and Arking, Dan E and Benjamin, Emelia J and Berenson, Gerald S and Bis, Josh C and Chen, Wei and Deo, Rajat and Ellinor, Patrick T and Heckbert, Susan R and Heiss, Gerardo and Hsueh, Wen-Chi and Keating, Brendan J and Kerr, Kathleen F and Li, Yun and Limacher, Marian C and Liu, Yongmei and Lubitz, Steven A and Marciante, Kristin D and Mehra, Reena and Meng, Yan A and Newman, Anne B and Newton-Cheh, Christopher and North, Kari E and Palmer, Cameron D and Psaty, Bruce M and Quibrera, P Miguel and Redline, Susan and Reiner, Alex P and Rotter, Jerome I and Schnabel, Renate B and Schork, Nicholas J and Singleton, Andrew B and Smith, J Gustav and Soliman, Elsayed Z and Srinivasan, Sathanur R and Zhang, Zhu-Ming and Zonderman, Alan B and Ferrucci, Luigi and Murray, Sarah S and Evans, Michele K and Sotoodehnia, Nona and Magnani, Jared W and Avery, Christy L} } @article {8015, title = {Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.}, journal = {Nat Genet}, volume = {45}, year = {2013}, month = {2013 Jun}, pages = {621-31}, abstract = {

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

}, keywords = {Animals, Arrhythmias, Cardiac, Gene Frequency, Genetic Loci, Genome-Wide Association Study, Heart Conduction System, Heart Rate, Humans, Metabolic Networks and Pathways, Polymorphism, Single Nucleotide, Quantitative Trait Loci}, issn = {1546-1718}, doi = {10.1038/ng.2610}, author = {den Hoed, Marcel and Eijgelsheim, Mark and Esko, T{\~o}nu and Brundel, Bianca J J M and Peal, David S and Evans, David M and Nolte, Ilja M and Segr{\`e}, Ayellet V and Holm, Hilma and Handsaker, Robert E and Westra, Harm-Jan and Johnson, Toby and Isaacs, Aaron and Yang, Jian and Lundby, Alicia and Zhao, Jing Hua and Kim, Young Jin and Go, Min Jin and Almgren, Peter and Bochud, Murielle and Boucher, Gabrielle and Cornelis, Marilyn C and Gudbjartsson, Daniel and Hadley, David and van der Harst, Pim and Hayward, Caroline and den Heijer, Martin and Igl, Wilmar and Jackson, Anne U and Kutalik, Zolt{\'a}n and Luan, Jian{\textquoteright}an and Kemp, John P and Kristiansson, Kati and Ladenvall, Claes and Lorentzon, Mattias and Montasser, May E and Njajou, Omer T and O{\textquoteright}Reilly, Paul F and Padmanabhan, Sandosh and St Pourcain, Beate and Rankinen, Tuomo and Salo, Perttu and Tanaka, Toshiko and Timpson, Nicholas J and Vitart, Veronique and Waite, Lindsay and Wheeler, William and Zhang, Weihua and Draisma, Harmen H M and Feitosa, Mary F and Kerr, Kathleen F and Lind, Penelope A and Mihailov, Evelin and Onland-Moret, N Charlotte and Song, Ci and Weedon, Michael N and Xie, Weijia and Yengo, Loic and Absher, Devin and Albert, Christine M and Alonso, Alvaro and Arking, Dan E and de Bakker, Paul I W and Balkau, Beverley and Barlassina, Cristina and Benaglio, Paola and Bis, Joshua C and Bouatia-Naji, Nabila and Brage, S{\o}ren and Chanock, Stephen J and Chines, Peter S and Chung, Mina and Darbar, Dawood and Dina, Christian and D{\"o}rr, Marcus and Elliott, Paul and Felix, Stephan B and Fischer, Krista and Fuchsberger, Christian and de Geus, Eco J C and Goyette, Philippe and Gudnason, Vilmundur and Harris, Tamara B and Hartikainen, Anna-Liisa and Havulinna, Aki S and Heckbert, Susan R and Hicks, Andrew A and Hofman, Albert and Holewijn, Suzanne and Hoogstra-Berends, Femke and Hottenga, Jouke-Jan and Jensen, Majken K and Johansson, Asa and Junttila, Juhani and K{\"a}{\"a}b, Stefan and Kanon, Bart and Ketkar, Shamika and Khaw, Kay-Tee and Knowles, Joshua W and Kooner, Angrad S and Kors, Jan A and Kumari, Meena and Milani, Lili and Laiho, P{\"a}ivi and Lakatta, Edward G and Langenberg, Claudia and Leusink, Maarten and Liu, Yongmei and Luben, Robert N and Lunetta, Kathryn L and Lynch, Stacey N and Markus, Marcello R P and Marques-Vidal, Pedro and Mateo Leach, Irene and McArdle, Wendy L and McCarroll, Steven A and Medland, Sarah E and Miller, Kathryn A and Montgomery, Grant W and Morrison, Alanna C and M{\"u}ller-Nurasyid, Martina and Navarro, Pau and Nelis, Mari and O{\textquoteright}Connell, Jeffrey R and O{\textquoteright}Donnell, Christopher J and Ong, Ken K and Newman, Anne B and Peters, Annette and Polasek, Ozren and Pouta, Anneli and Pramstaller, Peter P and Psaty, Bruce M and Rao, Dabeeru C and Ring, Susan M and Rossin, Elizabeth J and Rudan, Diana and Sanna, Serena and Scott, Robert A and Sehmi, Jaban S and Sharp, Stephen and Shin, Jordan T and Singleton, Andrew B and Smith, Albert V and Soranzo, Nicole and Spector, Tim D and Stewart, Chip and Stringham, Heather M and Tarasov, Kirill V and Uitterlinden, Andr{\'e} G and Vandenput, Liesbeth and Hwang, Shih-Jen and Whitfield, John B and Wijmenga, Cisca and Wild, Sarah H and Willemsen, Gonneke and Wilson, James F and Witteman, Jacqueline C M and Wong, Andrew and Wong, Quenna and Jamshidi, Yalda and Zitting, Paavo and Boer, Jolanda M A and Boomsma, Dorret I and Borecki, Ingrid B and van Duijn, Cornelia M and Ekelund, Ulf and Forouhi, Nita G and Froguel, Philippe and Hingorani, Aroon and Ingelsson, Erik and Kivimaki, Mika and Kronmal, Richard A and Kuh, Diana and Lind, Lars and Martin, Nicholas G and Oostra, Ben A and Pedersen, Nancy L and Quertermous, Thomas and Rotter, Jerome I and van der Schouw, Yvonne T and Verschuren, W M Monique and Walker, Mark and Albanes, Demetrius and Arnar, David O and Assimes, Themistocles L and Bandinelli, Stefania and Boehnke, Michael and de Boer, Rudolf A and Bouchard, Claude and Caulfield, W L Mark and Chambers, John C and Curhan, Gary and Cusi, Daniele and Eriksson, Johan and Ferrucci, Luigi and van Gilst, Wiek H and Glorioso, Nicola and de Graaf, Jacqueline and Groop, Leif and Gyllensten, Ulf and Hsueh, Wen-Chi and Hu, Frank B and Huikuri, Heikki V and Hunter, David J and Iribarren, Carlos and Isomaa, Bo and Jarvelin, Marjo-Riitta and Jula, Antti and K{\"a}h{\"o}nen, Mika and Kiemeney, Lambertus A and van der Klauw, Melanie M and Kooner, Jaspal S and Kraft, Peter and Iacoviello, Licia and Lehtim{\"a}ki, Terho and Lokki, Marja-Liisa L and Mitchell, Braxton D and Navis, Gerjan and Nieminen, Markku S and Ohlsson, Claes and Poulter, Neil R and Qi, Lu and Raitakari, Olli T and Rimm, Eric B and Rioux, John D and Rizzi, Federica and Rudan, Igor and Salomaa, Veikko and Sever, Peter S and Shields, Denis C and Shuldiner, Alan R and Sinisalo, Juha and Stanton, Alice V and Stolk, Ronald P and Strachan, David P and Tardif, Jean-Claude and Thorsteinsdottir, Unnur and Tuomilehto, Jaako and van Veldhuisen, Dirk J and Virtamo, Jarmo and Viikari, Jorma and Vollenweider, Peter and Waeber, G{\'e}rard and Widen, Elisabeth and Cho, Yoon Shin and Olsen, Jesper V and Visscher, Peter M and Willer, Cristen and Franke, Lude and Erdmann, Jeanette and Thompson, John R and Pfeufer, Arne and Sotoodehnia, Nona and Newton-Cheh, Christopher and Ellinor, Patrick T and Stricker, Bruno H Ch and Metspalu, Andres and Perola, Markus and Beckmann, Jacques S and Smith, George Davey and Stefansson, Kari and Wareham, Nicholas J and Munroe, Patricia B and Sibon, Ody C M and Milan, David J and Snieder, Harold and Samani, Nilesh J and Loos, Ruth J F} } @article {6585, title = {Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes.}, journal = {PLoS Genet}, volume = {10}, year = {2014}, month = {2014 Aug}, pages = {e1004517}, abstract = {

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 {\texttimes} 10(-94)}, keywords = {African Americans, Diabetes Mellitus, Type 2, Genome-Wide Association Study, HLA-B27 Antigen, HMGA2 Protein, Humans, KCNQ1 Potassium Channel, Mutant Chimeric Proteins, Polymorphism, Single Nucleotide, Transcription Factor 7-Like 2 Protein}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1004517}, author = {Ng, Maggie C Y and Shriner, Daniel and Chen, Brian H and Li, Jiang and Chen, Wei-Min and Guo, Xiuqing and Liu, Jiankang and Bielinski, Suzette J and Yanek, Lisa R and Nalls, Michael A and Comeau, Mary E and Rasmussen-Torvik, Laura J and Jensen, Richard A and Evans, Daniel S and Sun, Yan V and An, Ping and Patel, Sanjay R and Lu, Yingchang and Long, Jirong and Armstrong, Loren L and Wagenknecht, Lynne and Yang, Lingyao and Snively, Beverly M and Palmer, Nicholette D and Mudgal, Poorva and Langefeld, Carl D and Keene, Keith L and Freedman, Barry I and Mychaleckyj, Josyf C and Nayak, Uma and Raffel, Leslie J and Goodarzi, Mark O and Chen, Y-D Ida and Taylor, Herman A and Correa, Adolfo and Sims, Mario and Couper, David and Pankow, James S and Boerwinkle, Eric and Adeyemo, Adebowale and Doumatey, Ayo and Chen, Guanjie and Mathias, Rasika A and Vaidya, Dhananjay and Singleton, Andrew B and Zonderman, Alan B and Igo, Robert P and Sedor, John R and Kabagambe, Edmond K and Siscovick, David S and McKnight, Barbara and Rice, Kenneth and Liu, Yongmei and Hsueh, Wen-Chi and Zhao, Wei and Bielak, Lawrence F and Kraja, Aldi and Province, Michael A and Bottinger, Erwin P and Gottesman, Omri and Cai, Qiuyin and Zheng, Wei and Blot, William J and Lowe, William L and Pacheco, Jennifer A and Crawford, Dana C and Grundberg, Elin and Rich, Stephen S and Hayes, M Geoffrey and Shu, Xiao-Ou and Loos, Ruth J F and Borecki, Ingrid B and Peyser, Patricia A and Cummings, Steven R and Psaty, Bruce M and Fornage, Myriam and Iyengar, Sudha K and Evans, Michele K and Becker, Diane M and Kao, W H Linda and Wilson, James G and Rotter, Jerome I and Sale, Mich{\`e}le M and Liu, Simin and Rotimi, Charles N and Bowden, Donald W} } @article {7259, title = {Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans.}, journal = {Hum Mol Genet}, year = {2016}, month = {2016 Aug 29}, abstract = {

The electrocardiographic QRS duration, a measure of ventricular depolarization and conduction, is associated with cardiovascular mortality. While single nucleotide polymorphisms (SNPs) associated with QRS duration have been identified at 22 loci in populations of European descent, the genetic architecture of QRS duration in non-European populations is largely unknown. We therefore performed a genome-wide association study (GWAS) meta-analysis of QRS duration in 13,031 African Americans from ten cohorts and a transethnic GWAS meta-analysis with additional results from populations of European descent. In the African American GWAS, a single genome-wide significant SNP association was identified (rs3922844, P = 4 {\texttimes} 10(-14)) in intron 16 of SCN5A, a voltage-gated cardiac sodium channel gene. The QRS-prolonging rs3922844 C allele was also associated with decreased SCN5A RNA expression in human atrial tissue (P = 1.1 {\texttimes} 10(-4)). High density genotyping revealed that the SCN5A association region in African Americans was confined to intron 16. Transethnic GWAS meta-analysis identified novel SNP associations on chromosome 18 in MYL12A (rs1662342, P = 4.9 {\texttimes} 10(-8)) and chromosome 1 near CD1E and SPTA1 (rs7547997, P = 7.9 {\texttimes} 10(-9)). The 22 QRS loci previously identified in populations of European descent were enriched for significant SNP associations with QRS duration in African Americans (P = 9.9 {\texttimes} 10(-7)), and index SNP associations in or near SCN5A, SCN10A, CDKN1A, NFIA, HAND1, TBX5 and SETBP1 replicated in African Americans. In summary, rs3922844 was associated with QRS duration and SCN5A expression, two novel QRS loci were identified using transethnic meta-analysis, and a significant proportion of QRS-SNP associations discovered in populations of European descent were transferable to African Americans when adequate power was achieved.

}, issn = {1460-2083}, doi = {10.1093/hmg/ddw284}, author = {Evans, Daniel S and Avery, Christy L and Nalls, Mike A and Li, Guo and Barnard, John and Smith, Erin N and Tanaka, Toshiko and Butler, Anne M and Buxbaum, Sarah G and Alonso, Alvaro and Arking, Dan E and Berenson, Gerald S and Bis, Joshua C and Buyske, Steven and Carty, Cara L and Chen, Wei and Chung, Mina K and Cummings, Steven R and Deo, Rajat and Eaton, Charles B and Fox, Ervin R and Heckbert, Susan R and Heiss, Gerardo and Hindorff, Lucia A and Hsueh, Wen-Chi and Isaacs, Aaron and Jamshidi, Yalda and Kerr, Kathleen F and Liu, Felix and Liu, Yongmei and Lohman, Kurt K and Magnani, Jared W and Maher, Joseph F and Mehra, Reena and Meng, Yan A and Musani, Solomon K and Newton-Cheh, Christopher and North, Kari E and Psaty, Bruce M and Redline, Susan and Rotter, Jerome I and Schnabel, Renate B and Schork, Nicholas J and Shohet, Ralph V and Singleton, Andrew B and Smith, Jonathan D and Soliman, Elsayed Z and Srinivasan, Sathanur R and Taylor, Herman A and Van Wagoner, David R and Wilson, James G and Young, Taylor and Zhang, Zhu-Ming and Zonderman, Alan B and Evans, Michele K and Ferrucci, Luigi and Murray, Sarah S and Tranah, Gregory J and Whitsel, Eric A and Reiner, Alex P and Sotoodehnia, Nona} } @article {7600, title = {Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.}, journal = {Nat Commun}, volume = {8}, year = {2017}, month = {2017 Jul 19}, pages = {80}, abstract = {

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 {\texttimes} 10-8) or suggestively genome wide (p < 2.3 {\texttimes} 10-6). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.

}, issn = {2041-1723}, doi = {10.1038/s41467-017-00031-7}, author = {Zillikens, M Carola and Demissie, Serkalem and Hsu, Yi-Hsiang and Yerges-Armstrong, Laura M and Chou, Wen-Chi and Stolk, Lisette and Livshits, Gregory and Broer, Linda and Johnson, Toby and Koller, Daniel L and Kutalik, Zolt{\'a}n and Luan, Jian{\textquoteright}an and Malkin, Ida and Ried, Janina S and Smith, Albert V and Thorleifsson, Gudmar and Vandenput, Liesbeth and Hua Zhao, Jing and Zhang, Weihua and Aghdassi, Ali and {\r A}kesson, Kristina and Amin, Najaf and Baier, Leslie J and Barroso, In{\^e}s and Bennett, David A and Bertram, Lars and Biffar, Rainer and Bochud, Murielle and Boehnke, Michael and Borecki, Ingrid B and Buchman, Aron S and Byberg, Liisa and Campbell, Harry and Campos Obanda, Natalia and Cauley, Jane A and Cawthon, Peggy M and Cederberg, Henna and Chen, Zhao and Cho, Nam H and Jin Choi, Hyung and Claussnitzer, Melina and Collins, Francis and Cummings, Steven R and De Jager, Philip L and Demuth, Ilja and Dhonukshe-Rutten, Rosalie A M and Diatchenko, Luda and Eiriksdottir, Gudny and Enneman, Anke W and Erdos, Mike and Eriksson, Johan G and Eriksson, Joel and Estrada, Karol and Evans, Daniel S and Feitosa, Mary F and Fu, Mao and Garcia, Melissa and Gieger, Christian and Girke, Thomas and Glazer, Nicole L and Grallert, Harald and Grewal, Jagvir and Han, Bok-Ghee and Hanson, Robert L and Hayward, Caroline and Hofman, Albert and Hoffman, Eric P and Homuth, Georg and Hsueh, Wen-Chi and Hubal, Monica J and Hubbard, Alan and Huffman, Kim M and Husted, Lise B and Illig, Thomas and Ingelsson, Erik and Ittermann, Till and Jansson, John-Olov and Jordan, Joanne M and Jula, Antti and Karlsson, Magnus and Khaw, Kay-Tee and Kilpel{\"a}inen, Tuomas O and Klopp, Norman and Kloth, Jacqueline S L and Koistinen, Heikki A and Kraus, William E and Kritchevsky, Stephen and Kuulasmaa, Teemu and Kuusisto, Johanna and Laakso, Markku and Lahti, Jari and Lang, Thomas and Langdahl, Bente L and Launer, Lenore J and Lee, Jong-Young and Lerch, Markus M and Lewis, Joshua R and Lind, Lars and Lindgren, Cecilia and Liu, Yongmei and Liu, Tian and Liu, Youfang and Ljunggren, Osten and Lorentzon, Mattias and Luben, Robert N and Maixner, William and McGuigan, Fiona E and Medina-G{\'o}mez, Carolina and Meitinger, Thomas and Melhus, H{\r a}kan and Mellstr{\"o}m, Dan and Melov, Simon and Micha{\"e}lsson, Karl and Mitchell, Braxton D and Morris, Andrew P and Mosekilde, Leif and Newman, Anne and Nielson, Carrie M and O{\textquoteright}Connell, Jeffrey R and Oostra, Ben A and Orwoll, Eric S and Palotie, Aarno and Parker, Stephen C J and Peacock, Munro and Perola, Markus and Peters, Annette and Polasek, Ozren and Prince, Richard L and R{\"a}ikk{\"o}nen, Katri and Ralston, Stuart H and Ripatti, Samuli and Robbins, John A and Rotter, Jerome I and Rudan, Igor and Salomaa, Veikko and Satterfield, Suzanne and Schadt, Eric E and Schipf, Sabine and Scott, Laura and Sehmi, Joban and Shen, Jian and Soo Shin, Chan and Sigurdsson, Gunnar and Smith, Shad and Soranzo, Nicole and Stan{\v c}{\'a}kov{\'a}, Alena and Steinhagen-Thiessen, Elisabeth and Streeten, Elizabeth A and Styrkarsdottir, Unnur and Swart, Karin M A and Tan, Sian-Tsung and Tarnopolsky, Mark A and Thompson, Patricia and Thomson, Cynthia A and Thorsteinsdottir, Unnur and Tikkanen, Emmi and Tranah, Gregory J and Tuomilehto, Jaakko and van Schoor, Natasja M and Verma, Arjun and Vollenweider, Peter and V{\"o}lzke, Henry and Wactawski-Wende, Jean and Walker, Mark and Weedon, Michael N and Welch, Ryan and Wichmann, H-Erich and Widen, Elisabeth and Williams, Frances M K and Wilson, James F and Wright, Nicole C and Xie, Weijia and Yu, Lei and Zhou, Yanhua and Chambers, John C and D{\"o}ring, Angela and van Duijn, Cornelia M and Econs, Michael J and Gudnason, Vilmundur and Kooner, Jaspal S and Psaty, Bruce M and Spector, Timothy D and Stefansson, Kari and Rivadeneira, Fernando and Uitterlinden, Andr{\'e} G and Wareham, Nicholas J and Ossowski, Vicky and Waterworth, Dawn and Loos, Ruth J F and Karasik, David and Harris, Tamara B and Ohlsson, Claes and Kiel, Douglas P} }