@article {6552, title = {Meta-analysis of loci associated with age at natural menopause in African-American women.}, journal = {Hum Mol Genet}, volume = {23}, year = {2014}, month = {2014 Jun 15}, pages = {3327-42}, abstract = {

Age at menopause marks the end of a woman{\textquoteright}s reproductive life and its timing associates with risks for cancer, cardiovascular and bone disorders. GWAS and candidate gene studies conducted in women of European ancestry have identified 27 loci associated with age at menopause. The relevance of these loci to women of African ancestry has not been previously studied. We therefore sought to uncover additional menopause loci and investigate the relevance of European menopause loci by performing a GWAS meta-analysis in 6510 women with African ancestry derived from 11 studies across the USA. We did not identify any additional loci significantly associated with age at menopause in African Americans. We replicated the associations between six loci and age at menopause (P-value < 0.05): AMHR2, RHBLD2, PRIM1, HK3/UMC1, BRSK1/TMEM150B and MCM8. In addition, associations of 14 loci are directionally consistent with previous reports. We provide evidence that genetic variants influencing reproductive traits identified in European populations are also important in women of African ancestry residing in USA.

}, keywords = {African Americans, Age Factors, Chromosomes, Human, European Continental Ancestry Group, Female, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Humans, Menopause, United States}, issn = {1460-2083}, doi = {10.1093/hmg/ddu041}, author = {Chen, Christina T L and Liu, Ching-Ti and Chen, Gary K and Andrews, Jeanette S and Arnold, Alice M and Dreyfus, Jill and Franceschini, Nora and Garcia, Melissa E and Kerr, Kathleen F and Li, Guo and Lohman, Kurt K and Musani, Solomon K and Nalls, Michael A and Raffel, Leslie J and Smith, Jennifer and Ambrosone, Christine B and Bandera, Elisa V and Bernstein, Leslie and Britton, Angela and Brzyski, Robert G and Cappola, Anne and Carlson, Christopher S and Couper, David and Deming, Sandra L and Goodarzi, Mark O and Heiss, Gerardo and John, Esther M and Lu, Xiaoning and Le Marchand, Lo{\"\i}c and Marciante, Kristin and McKnight, Barbara and Millikan, Robert and Nock, Nora L and Olshan, Andrew F and Press, Michael F and Vaiyda, Dhananjay and Woods, Nancy F and Taylor, Herman A and Zhao, Wei and Zheng, Wei and Evans, Michele K and Harris, Tamara B and Henderson, Brian E and Kardia, Sharon L R and Kooperberg, Charles and Liu, Yongmei and Mosley, Thomas H and Psaty, Bruce and Wellons, Melissa and Windham, Beverly G and Zonderman, Alan B and Cupples, L Adrienne and Demerath, Ellen W and Haiman, Christopher and Murabito, Joanne M and Rajkovic, Aleksandar} } @article {6686, title = {Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility.}, journal = {Nat Commun}, volume = {6}, year = {2015}, month = {2015}, pages = {5897}, abstract = {

Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF=1.4\%) with lower FG (β=-0.09{\textpm}0.01 mmol l(-1), P=3.4 {\texttimes} 10(-12)), T2D risk (OR[95\%CI]=0.86[0.76-0.96], P=0.010), early insulin secretion (β=-0.07{\textpm}0.035 pmolinsulin mmolglucose(-1), P=0.048), but higher 2-h glucose (β=0.16{\textpm}0.05 mmol l(-1), P=4.3 {\texttimes} 10(-4)). We identify a gene-based association with FG at G6PC2 (pSKAT=6.8 {\texttimes} 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF=20\%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (β=0.02{\textpm}0.004 mmol l(-1), P=1.3 {\texttimes} 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.

}, keywords = {African Continental Ancestry Group, Blood Glucose, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Exome, Fasting, Genetic Association Studies, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Glucagon-Like Peptide-1 Receptor, Glucose-6-Phosphatase, Humans, Insulin, Mutation Rate, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide}, issn = {2041-1723}, doi = {10.1038/ncomms6897}, author = {Wessel, Jennifer and Chu, Audrey Y and Willems, Sara M and Wang, Shuai and Yaghootkar, Hanieh and Brody, Jennifer A and Dauriz, Marco and Hivert, Marie-France and Raghavan, Sridharan and Lipovich, Leonard and Hidalgo, Bertha and Fox, Keolu and Huffman, Jennifer E and An, Ping and Lu, Yingchang and Rasmussen-Torvik, Laura J and Grarup, Niels and Ehm, Margaret G and Li, Li and Baldridge, Abigail S and Stan{\v c}{\'a}kov{\'a}, Alena and Abrol, Ravinder and Besse, C{\'e}line and Boland, Anne and Bork-Jensen, Jette and Fornage, Myriam and Freitag, Daniel F and Garcia, Melissa E and Guo, Xiuqing and Hara, Kazuo and Isaacs, Aaron and Jakobsdottir, Johanna and Lange, Leslie A and Layton, Jill C and Li, Man and Hua Zhao, Jing and Meidtner, Karina and Morrison, Alanna C and Nalls, Mike A and Peters, Marjolein J and Sabater-Lleal, Maria and Schurmann, Claudia and Silveira, Angela and Smith, Albert V and Southam, Lorraine and Stoiber, Marcus H and Strawbridge, Rona J and Taylor, Kent D and Varga, Tibor V and Allin, Kristine H and Amin, Najaf and Aponte, Jennifer L and Aung, Tin and Barbieri, Caterina and Bihlmeyer, Nathan A and Boehnke, Michael and Bombieri, Cristina and Bowden, Donald W and Burns, Sean M and Chen, Yuning and Chen, Yii-DerI and Cheng, Ching-Yu and Correa, Adolfo and Czajkowski, Jacek and Dehghan, Abbas and Ehret, Georg B and Eiriksdottir, Gudny and Escher, Stefan A and Farmaki, Aliki-Eleni and Fr{\r a}nberg, Mattias and Gambaro, Giovanni and Giulianini, Franco and Goddard, William A and Goel, Anuj and Gottesman, Omri and Grove, Megan L and Gustafsson, Stefan and Hai, Yang and Hallmans, G{\"o}ran and Heo, Jiyoung and Hoffmann, Per and Ikram, Mohammad K and Jensen, Richard A and J{\o}rgensen, Marit E and J{\o}rgensen, Torben and Karaleftheri, Maria and Khor, Chiea C and Kirkpatrick, Andrea and Kraja, Aldi T and Kuusisto, Johanna and Lange, Ethan M and Lee, I T and Lee, Wen-Jane and Leong, Aaron and Liao, Jiemin and Liu, Chunyu and Liu, Yongmei and Lindgren, Cecilia M and Linneberg, Allan and Malerba, Giovanni and Mamakou, Vasiliki and Marouli, Eirini and Maruthur, Nisa M and Matchan, Angela and McKean-Cowdin, Roberta and McLeod, Olga and Metcalf, Ginger A and Mohlke, Karen L and Muzny, Donna M and Ntalla, Ioanna and Palmer, Nicholette D and Pasko, Dorota and Peter, Andreas and Rayner, Nigel W and Renstrom, Frida and Rice, Ken and Sala, Cinzia F and Sennblad, Bengt and Serafetinidis, Ioannis and Smith, Jennifer A and Soranzo, Nicole and Speliotes, Elizabeth K and Stahl, Eli A and Stirrups, Kathleen and Tentolouris, Nikos and Thanopoulou, Anastasia and Torres, Mina and Traglia, Michela and Tsafantakis, Emmanouil and Javad, Sundas and Yanek, Lisa R and Zengini, Eleni and Becker, Diane M and Bis, Joshua C and Brown, James B and Cupples, L Adrienne and Hansen, Torben and Ingelsson, Erik and Karter, Andrew J and Lorenzo, Carlos and Mathias, Rasika A and Norris, Jill M and Peloso, Gina M and Sheu, Wayne H-H and Toniolo, Daniela and Vaidya, Dhananjay and Varma, Rohit and Wagenknecht, Lynne E and Boeing, Heiner and Bottinger, Erwin P and Dedoussis, George and Deloukas, Panos and Ferrannini, Ele and Franco, Oscar H and Franks, Paul W and Gibbs, Richard A and Gudnason, Vilmundur and Hamsten, Anders and Harris, Tamara B and Hattersley, Andrew T and Hayward, Caroline and Hofman, Albert and Jansson, Jan-H{\r a}kan and Langenberg, Claudia and Launer, Lenore J and Levy, Daniel and Oostra, Ben A and O{\textquoteright}Donnell, Christopher J and O{\textquoteright}Rahilly, Stephen and Padmanabhan, Sandosh and Pankow, James S and Polasek, Ozren and Province, Michael A and Rich, Stephen S and Ridker, Paul M and Rudan, Igor and Schulze, Matthias B and Smith, Blair H and Uitterlinden, Andr{\'e} G and Walker, Mark and Watkins, Hugh and Wong, Tien Y and Zeggini, Eleftheria and Laakso, Markku and Borecki, Ingrid B and Chasman, Daniel I and Pedersen, Oluf and Psaty, Bruce M and Tai, E Shyong and van Duijn, Cornelia M and Wareham, Nicholas J and Waterworth, Dawn M and Boerwinkle, Eric and Kao, W H Linda and Florez, Jose C and Loos, Ruth J F and Wilson, James G and Frayling, Timothy M and Siscovick, David S and Dupuis, Jos{\'e}e and Rotter, Jerome I and Meigs, James B and Scott, Robert A and Goodarzi, Mark O} } @article {7573, title = {Exome-wide association study of plasma lipids in >300,000 individuals.}, journal = {Nat Genet}, volume = {49}, year = {2017}, month = {2017 Dec}, pages = {1758-1766}, abstract = {

We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.

}, keywords = {Coronary Artery Disease, Diabetes Mellitus, Type 2, Exome, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Variation, Genotype, Humans, Lipids, Macular Degeneration, Phenotype, Risk Factors}, issn = {1546-1718}, doi = {10.1038/ng.3977}, author = {Liu, Dajiang J and Peloso, Gina M and Yu, Haojie and Butterworth, Adam S and Wang, Xiao and Mahajan, Anubha and Saleheen, Danish and Emdin, Connor and Alam, Dewan and Alves, Alexessander Couto and Amouyel, Philippe and Di Angelantonio, Emanuele and Arveiler, Dominique and Assimes, Themistocles L and Auer, Paul L and Baber, Usman and Ballantyne, Christie M and Bang, Lia E and Benn, Marianne and Bis, Joshua C and Boehnke, Michael and Boerwinkle, Eric and Bork-Jensen, Jette and Bottinger, Erwin P and Brandslund, Ivan and Brown, Morris and Busonero, Fabio and Caulfield, Mark J and Chambers, John C and Chasman, Daniel I and Chen, Y Eugene and Chen, Yii-Der Ida and Chowdhury, Rajiv and Christensen, Cramer and Chu, Audrey Y and Connell, John M and Cucca, Francesco and Cupples, L Adrienne and Damrauer, Scott M and Davies, Gail and Deary, Ian J and Dedoussis, George and Denny, Joshua C and Dominiczak, Anna and Dub{\'e}, Marie-Pierre and Ebeling, Tapani and Eiriksdottir, Gudny and Esko, T{\~o}nu and Farmaki, Aliki-Eleni and Feitosa, Mary F and Ferrario, Marco and Ferrieres, Jean and Ford, Ian and Fornage, Myriam and Franks, Paul W and Frayling, Timothy M and Frikke-Schmidt, Ruth and Fritsche, Lars G and Frossard, Philippe and Fuster, Valentin and Ganesh, Santhi K and Gao, Wei and Garcia, Melissa E and Gieger, Christian and Giulianini, Franco and Goodarzi, Mark O and Grallert, Harald and Grarup, Niels and Groop, Leif and Grove, Megan L and Gudnason, Vilmundur and Hansen, Torben and Harris, Tamara B and Hayward, Caroline and Hirschhorn, Joel N and Holmen, Oddgeir L and Huffman, Jennifer and Huo, Yong and Hveem, Kristian and Jabeen, Sehrish and Jackson, Anne U and Jakobsdottir, Johanna and Jarvelin, Marjo-Riitta and Jensen, Gorm B and J{\o}rgensen, Marit E and Jukema, J Wouter and Justesen, Johanne M and Kamstrup, Pia R and Kanoni, Stavroula and Karpe, Fredrik and Kee, Frank and Khera, Amit V and Klarin, Derek and Koistinen, Heikki A and Kooner, Jaspal S and Kooperberg, Charles and Kuulasmaa, Kari and Kuusisto, Johanna and Laakso, Markku and Lakka, Timo and Langenberg, Claudia and Langsted, Anne and Launer, Lenore J and Lauritzen, Torsten and Liewald, David C M and Lin, Li An and Linneberg, Allan and Loos, Ruth J F and Lu, Yingchang and Lu, Xiangfeng and M{\"a}gi, Reedik and M{\"a}larstig, Anders and Manichaikul, Ani and Manning, Alisa K and M{\"a}ntyselk{\"a}, Pekka and Marouli, Eirini and Masca, Nicholas G D and Maschio, Andrea and Meigs, James B and Melander, Olle and Metspalu, Andres and Morris, Andrew P and Morrison, Alanna C and Mulas, Antonella and M{\"u}ller-Nurasyid, Martina and Munroe, Patricia B and Neville, Matt J and Nielsen, Jonas B and Nielsen, Sune F and Nordestgaard, B{\o}rge G and Ordovas, Jose M and Mehran, Roxana and O{\textquoteright}Donnell, Christoper J and Orho-Melander, Marju and Molony, Cliona M and Muntendam, Pieter and Padmanabhan, Sandosh and Palmer, Colin N A and Pasko, Dorota and Patel, Aniruddh P and Pedersen, Oluf and Perola, Markus and Peters, Annette and Pisinger, Charlotta and Pistis, Giorgio and Polasek, Ozren and Poulter, Neil and Psaty, Bruce M and Rader, Daniel J and Rasheed, Asif and Rauramaa, Rainer and Reilly, Dermot F and Reiner, Alex P and Renstrom, Frida and Rich, Stephen S and Ridker, Paul M and Rioux, John D and Robertson, Neil R and Roden, Dan M and Rotter, Jerome I and Rudan, Igor and Salomaa, Veikko and Samani, Nilesh J and Sanna, Serena and Sattar, Naveed and Schmidt, Ellen M and Scott, Robert A and Sever, Peter and Sevilla, Raquel S and Shaffer, Christian M and Sim, Xueling and Sivapalaratnam, Suthesh and Small, Kerrin S and Smith, Albert V and Smith, Blair H and Somayajula, Sangeetha and Southam, Lorraine and Spector, Timothy D and Speliotes, Elizabeth K and Starr, John M and Stirrups, Kathleen E and Stitziel, Nathan and Strauch, Konstantin and Stringham, Heather M and Surendran, Praveen and Tada, Hayato and Tall, Alan R and Tang, Hua and Tardif, Jean-Claude and Taylor, Kent D and Trompet, Stella and Tsao, Philip S and Tuomilehto, Jaakko and Tybjaerg-Hansen, Anne and van Zuydam, Natalie R and Varbo, Anette and Varga, Tibor V and Virtamo, Jarmo and Waldenberger, Melanie and Wang, Nan and Wareham, Nick J and Warren, Helen R and Weeke, Peter E and Weinstock, Joshua and Wessel, Jennifer and Wilson, James G and Wilson, Peter W F and Xu, Ming and Yaghootkar, Hanieh and Young, Robin and Zeggini, Eleftheria and Zhang, He and Zheng, Neil S and Zhang, Weihua and Zhang, Yan and Zhou, Wei and Zhou, Yanhua and Zoledziewska, Magdalena and Howson, Joanna M M and Danesh, John and McCarthy, Mark I and Cowan, Chad A and Abecasis, Goncalo and Deloukas, Panos and Musunuru, Kiran and Willer, Cristen J and Kathiresan, Sekar} }