@article {6178, title = {Association of genetic loci with sleep apnea in European Americans and African-Americans: the Candidate Gene Association Resource (CARe).}, journal = {PLoS One}, volume = {7}, year = {2012}, month = {2012}, pages = {e48836}, abstract = {

Although obstructive sleep apnea (OSA) is known to have a strong familial basis, no genetic polymorphisms influencing apnea risk have been identified in cross-cohort analyses. We utilized the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe) to identify sleep apnea susceptibility loci. Using a panel of 46,449 polymorphisms from roughly 2,100 candidate genes on a customized Illumina iSelect chip, we tested for association with the apnea hypopnea index (AHI) as well as moderate to severe OSA (AHI>=15) in 3,551 participants of the Cleveland Family Study and two cohorts participating in the Sleep Heart Health Study.Among 647 African-Americans, rs11126184 in the pleckstrin (PLEK) gene was associated with OSA while rs7030789 in the lysophosphatidic acid receptor 1 (LPAR1) gene was associated with AHI using a chip-wide significance threshold of p-value<2{\texttimes}10(-6). Among 2,904 individuals of European ancestry, rs1409986 in the prostaglandin E2 receptor (PTGER3) gene was significantly associated with OSA. Consistency of effects between rs7030789 and rs1409986 in LPAR1 and PTGER3 and apnea phenotypes were observed in independent clinic-based cohorts.Novel genetic loci for apnea phenotypes were identified through the use of customized gene chips and meta-analyses of cohort data with replication in clinic-based samples. The identified SNPs all lie in genes associated with inflammation suggesting inflammation may play a role in OSA pathogenesis.

}, keywords = {Adult, African Americans, Aged, Alleles, European Continental Ancestry Group, Female, Genetic Association Studies, Genetic Loci, Genetic Predisposition to Disease, Genotype, Humans, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Polysomnography, Sleep Apnea, Obstructive}, issn = {1932-6203}, doi = {10.1371/journal.pone.0048836}, author = {Patel, Sanjay R and Goodloe, Robert and De, Gourab and Kowgier, Matthew and Weng, Jia and Buxbaum, Sarah G and Cade, Brian and Fulop, Tibor and Gharib, Sina A and Gottlieb, Daniel J and Hillman, David and Larkin, Emma K and Lauderdale, Diane S and Li, Li and Mukherjee, Sutapa and Palmer, Lyle and Zee, Phyllis and Zhu, Xiaofeng and Redline, Susan} } @article {6368, title = {Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of European descent confirm known loci and reveal several novel associations.}, journal = {Hum Mol Genet}, volume = {23}, year = {2014}, month = {2014 May 01}, pages = {2498-510}, abstract = {

Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57 412 individuals of European descent from 22 cohorts collaborating with the NHLBI{\textquoteright}s Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20-80 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes \~{}50 000 cosmopolitan tagged SNPs across \~{}2100 cardiovascular-related genes. Each trait was modeled as a function of age, study site and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci for WC were observed. For WHR analyses, three novel loci were significantly associated (P < 2.4 {\texttimes} 10(-6)). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR (β {\textpm} SE, 0.048 {\textpm} 0.008, P = 7.7 {\texttimes} 10(-9)) as was rs7302703-G in HOXC10 (β = 0.044 {\textpm} 0.008, P = 2.9 {\texttimes} 10(-7)) and rs936108-C in PEMT (β = 0.035 {\textpm} 0.007, P = 1.9 {\texttimes} 10(-6)). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 (β = 0.10 {\textpm} 0.02, P = 1.9 {\texttimes} 10(-6)) and rs1037575-A in ATBDB4 (β = 0.046 {\textpm} 0.01, P = 2.2 {\texttimes} 10(-6)), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue.

}, keywords = {Adiposity, Adult, Aged, Aged, 80 and over, Body Mass Index, European Continental Ancestry Group, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Waist Circumference, Waist-Hip Ratio, Young Adult}, issn = {1460-2083}, doi = {10.1093/hmg/ddt626}, author = {Yoneyama, Sachiko and Guo, Yiran and Lanktree, Matthew B and Barnes, Michael R and Elbers, Clara C and Karczewski, Konrad J and Padmanabhan, Sandosh and Bauer, Florianne and Baumert, Jens and Beitelshees, Amber and Berenson, Gerald S and Boer, Jolanda M A and Burke, Gregory and Cade, Brian and Chen, Wei and Cooper-Dehoff, Rhonda M and Gaunt, Tom R and Gieger, Christian and Gong, Yan and Gorski, Mathias and Heard-Costa, Nancy and Johnson, Toby and Lamonte, Michael J and McDonough, Caitrin and Monda, Keri L and Onland-Moret, N Charlotte and Nelson, Christopher P and O{\textquoteright}Connell, Jeffrey R and Ordovas, Jose and Peter, Inga and Peters, Annette and Shaffer, Jonathan and Shen, Haiqinq and Smith, Erin and Speilotes, Liz and Thomas, Fridtjof and Thorand, Barbara and Monique Verschuren, W M and Anand, Sonia S and Dominiczak, Anna and Davidson, Karina W and Hegele, Robert A and Heid, Iris and Hofker, Marten H and Huggins, Gordon S and Illig, Thomas and Johnson, Julie A and Kirkland, Susan and K{\"o}nig, Wolfgang and Langaee, Taimour Y and McCaffery, Jeanne and Melander, Olle and Mitchell, Braxton D and Munroe, Patricia and Murray, Sarah S and Papanicolaou, George and Redline, Susan and Reilly, Muredach and Samani, Nilesh J and Schork, Nicholas J and van der Schouw, Yvonne T and Shimbo, Daichi and Shuldiner, Alan R and Tobin, Martin D and Wijmenga, Cisca and Yusuf, Salim and Hakonarson, Hakon and Lange, Leslie A and Demerath, Ellen W and Fox, Caroline S and North, Kari E and Reiner, Alex P and Keating, Brendan and Taylor, Kira C} } @article {7976, title = {Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.}, journal = {Nat Commun}, volume = {10}, year = {2019}, month = {2019 01 22}, pages = {376}, abstract = {

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.

}, keywords = {Adolescent, Adult, African Continental Ancestry Group, Aged, Aged, 80 and over, Asian Continental Ancestry Group, Brazil, Calcium-Binding Proteins, Cholesterol, Cholesterol, HDL, Cholesterol, LDL, European Continental Ancestry Group, Exercise, Female, Genetic Loci, Genome-Wide Association Study, Genotype, Hispanic Americans, Humans, LIM-Homeodomain Proteins, Lipid Metabolism, Lipids, Male, Membrane Proteins, Microtubule-Associated Proteins, Middle Aged, Muscle Proteins, Nerve Tissue Proteins, Transcription Factors, Triglycerides, Young Adult}, issn = {2041-1723}, doi = {10.1038/s41467-018-08008-w}, author = {Kilpel{\"a}inen, Tuomas O and Bentley, Amy R and Noordam, Raymond and Sung, Yun Ju and Schwander, Karen and Winkler, Thomas W and Jakupovi{\'c}, Hermina and Chasman, Daniel I and Manning, Alisa and Ntalla, Ioanna and Aschard, Hugues and Brown, Michael R and de Las Fuentes, Lisa and Franceschini, Nora and Guo, Xiuqing and Vojinovic, Dina and Aslibekyan, Stella and Feitosa, Mary F and Kho, Minjung and Musani, Solomon K and Richard, Melissa and Wang, Heming and Wang, Zhe and Bartz, Traci M and Bielak, Lawrence F and Campbell, Archie and Dorajoo, Rajkumar and Fisher, Virginia and Hartwig, Fernando P and Horimoto, Andrea R V R and Li, Changwei and Lohman, Kurt K and Marten, Jonathan and Sim, Xueling and Smith, Albert V and Tajuddin, Salman M and Alver, Maris and Amini, Marzyeh and Boissel, Mathilde and Chai, Jin Fang and Chen, Xu and Divers, Jasmin and Evangelou, Evangelos and Gao, Chuan and Graff, Mariaelisa and Harris, Sarah E and He, Meian and Hsu, Fang-Chi and Jackson, Anne U and Zhao, Jing Hua and Kraja, Aldi T and Kuhnel, Brigitte and Laguzzi, Federica and Lyytik{\"a}inen, Leo-Pekka and Nolte, Ilja M and Rauramaa, Rainer and Riaz, Muhammad and Robino, Antonietta and Rueedi, Rico and Stringham, Heather M and Takeuchi, Fumihiko and van der Most, Peter J and Varga, Tibor V and Verweij, Niek and Ware, Erin B and Wen, Wanqing and Li, Xiaoyin and Yanek, Lisa R and Amin, Najaf and Arnett, Donna K and Boerwinkle, Eric and Brumat, Marco and Cade, Brian and Canouil, Micka{\"e}l and Chen, Yii-Der Ida and Concas, Maria Pina and Connell, John and de Mutsert, Ren{\'e}e and de Silva, H Janaka and de Vries, Paul S and Demirkan, Ayse and Ding, Jingzhong and Eaton, Charles B and Faul, Jessica D and Friedlander, Yechiel and Gabriel, Kelley P and Ghanbari, Mohsen and Giulianini, Franco and Gu, Chi Charles and Gu, Dongfeng and Harris, Tamara B and He, Jiang and Heikkinen, Sami and Heng, Chew-Kiat and Hunt, Steven C and Ikram, M Arfan and Jonas, Jost B and Koh, Woon-Puay and Komulainen, Pirjo and Krieger, Jose E and Kritchevsky, Stephen B and Kutalik, Zolt{\'a}n and Kuusisto, Johanna and Langefeld, Carl D and Langenberg, Claudia and Launer, Lenore J and Leander, Karin and Lemaitre, Rozenn N and Lewis, Cora E and Liang, Jingjing and Liu, Jianjun and M{\"a}gi, Reedik and Manichaikul, Ani and Meitinger, Thomas and Metspalu, Andres and Milaneschi, Yuri and Mohlke, Karen L and Mosley, Thomas H and Murray, Alison D and Nalls, Mike A and Nang, Ei-Ei Khaing and Nelson, Christopher P and Nona, Sotoodehnia and Norris, Jill M and Nwuba, Chiamaka Vivian and O{\textquoteright}Connell, Jeff and Palmer, Nicholette D and Papanicolau, George J and Pazoki, Raha and Pedersen, Nancy L and Peters, Annette and Peyser, Patricia A and Polasek, Ozren and Porteous, David J and Poveda, Alaitz and Raitakari, Olli T and Rich, Stephen S and Risch, Neil and Robinson, Jennifer G and Rose, Lynda M and Rudan, Igor and Schreiner, Pamela J and Scott, Robert A and Sidney, Stephen S and Sims, Mario and Smith, Jennifer A and Snieder, Harold and Sofer, Tamar and Starr, John M and Sternfeld, Barbara and Strauch, Konstantin and Tang, Hua and Taylor, Kent D and Tsai, Michael Y and Tuomilehto, Jaakko and Uitterlinden, Andr{\'e} G and van der Ende, M Yldau and van Heemst, Diana and Voortman, Trudy and Waldenberger, Melanie and Wennberg, Patrik and Wilson, Gregory and Xiang, Yong-Bing and Yao, Jie and Yu, Caizheng and Yuan, Jian-Min and Zhao, Wei and Zonderman, Alan B and Becker, Diane M and Boehnke, Michael and Bowden, Donald W and de Faire, Ulf and Deary, Ian J and Elliott, Paul and Esko, T{\~o}nu and Freedman, Barry I and Froguel, Philippe and Gasparini, Paolo and Gieger, Christian and Kato, Norihiro and Laakso, Markku and Lakka, Timo A and Lehtim{\"a}ki, Terho and Magnusson, Patrik K E and Oldehinkel, Albertine J and Penninx, Brenda W J H and Samani, Nilesh J and Shu, Xiao-Ou and van der Harst, Pim and van Vliet-Ostaptchouk, Jana V and Vollenweider, Peter and Wagenknecht, Lynne E and Wang, Ya X and Wareham, Nicholas J and Weir, David R and Wu, Tangchun and Zheng, Wei and Zhu, Xiaofeng and Evans, Michele K and Franks, Paul W and Gudnason, Vilmundur and Hayward, Caroline and Horta, Bernardo L and Kelly, Tanika N and Liu, Yongmei and North, Kari E and Pereira, Alexandre C and Ridker, Paul M and Tai, E Shyong and van Dam, Rob M and Fox, Ervin R and Kardia, Sharon L R and Liu, Ching-Ti and Mook-Kanamori, Dennis O and Province, Michael A and Redline, Susan and van Duijn, Cornelia M and Rotter, Jerome I and Kooperberg, Charles B and Gauderman, W James and Psaty, Bruce M and Rice, Kenneth and Munroe, Patricia B and Fornage, Myriam and Cupples, L Adrienne and Rotimi, Charles N and Morrison, Alanna C and Rao, Dabeeru C and Loos, Ruth J F} }