@article {6072, title = {Genome-wide association study of retinopathy in individuals without diabetes.}, journal = {PLoS One}, volume = {8}, year = {2013}, month = {2013}, pages = {e54232}, abstract = {

BACKGROUND: Mild retinopathy (microaneurysms or dot-blot hemorrhages) is observed in persons without diabetes or hypertension and may reflect microvascular disease in other organs. We conducted a genome-wide association study (GWAS) of mild retinopathy in persons without diabetes.

METHODS: A working group agreed on phenotype harmonization, covariate selection and analytic plans for within-cohort GWAS. An inverse-variance weighted fixed effects meta-analysis was performed with GWAS results from six cohorts of 19,411 Caucasians. The primary analysis included individuals without diabetes and secondary analyses were stratified by hypertension status. We also singled out the results from single nucleotide polymorphisms (SNPs) previously shown to be associated with diabetes and hypertension, the two most common causes of retinopathy.

RESULTS: No SNPs reached genome-wide significance in the primary analysis or the secondary analysis of participants with hypertension. SNP, rs12155400, in the histone deacetylase 9 gene (HDAC9) on chromosome 7, was associated with retinopathy in analysis of participants without hypertension, -1.3{\textpm}0.23 (beta {\textpm} standard error), p = 6.6{\texttimes}10(-9). Evidence suggests this was a false positive finding. The minor allele frequency was low (\~{}2\%), the quality of the imputation was moderate (r(2) \~{}0.7), and no other common variants in the HDAC9 gene were associated with the outcome. SNPs found to be associated with diabetes and hypertension in other GWAS were not associated with retinopathy in persons without diabetes or in subgroups with or without hypertension.

CONCLUSIONS: This GWAS of retinopathy in individuals without diabetes showed little evidence of genetic associations. Further studies are needed to identify genes associated with these signs in order to help unravel novel pathways and determinants of microvascular diseases.

}, keywords = {Aged, Aged, 80 and over, Female, Genome-Wide Association Study, Genotype, Histone Deacetylases, Humans, Hypertension, Male, Polymorphism, Single Nucleotide, Repressor Proteins, Retinal Diseases}, issn = {1932-6203}, doi = {10.1371/journal.pone.0054232}, author = {Jensen, Richard A and Sim, Xueling and Li, Xiaohui and Cotch, Mary Frances and Ikram, M Kamran and Holliday, Elizabeth G and Eiriksdottir, Gudny and Harris, Tamara B and Jonasson, Fridbert and Klein, Barbara E K and Launer, Lenore J and Smith, Albert Vernon and Boerwinkle, Eric and Cheung, Ning and Hewitt, Alex W and Liew, Gerald and Mitchell, Paul and Wang, Jie Jin and Attia, John and Scott, Rodney and Glazer, Nicole L and Lumley, Thomas and McKnight, Barbara and Psaty, Bruce M and Taylor, Kent and Hofman, Albert and de Jong, Paulus T V M and Rivadeneira, Fernando and Uitterlinden, Andr{\'e} G and Tay, Wan-Ting and Teo, Yik Ying and Seielstad, Mark and Liu, Jianjun and Cheng, Ching-Yu and Saw, Seang-Mei and Aung, Tin and Ganesh, Santhi K and O{\textquoteright}Donnell, Christopher J and Nalls, Mike A and Wiggins, Kerri L and Kuo, Jane Z and van Duijn, Cornelia M and Gudnason, Vilmundur and Klein, Ronald and Siscovick, David S and Rotter, Jerome I and Tai, E Shong and Vingerling, Johannes and Wong, Tien Y} } @article {5875, title = {Insights into the genetic architecture of early stage age-related macular degeneration: a genome-wide association study meta-analysis.}, journal = {PLoS One}, volume = {8}, year = {2013}, month = {2013}, pages = {e53830}, abstract = {

Genetic factors explain a majority of risk variance for age-related macular degeneration (AMD). While genome-wide association studies (GWAS) for late AMD implicate genes in complement, inflammatory and lipid pathways, the genetic architecture of early AMD has been relatively under studied. We conducted a GWAS meta-analysis of early AMD, including 4,089 individuals with prevalent signs of early AMD (soft drusen and/or retinal pigment epithelial changes) and 20,453 individuals without these signs. For various published late AMD risk loci, we also compared effect sizes between early and late AMD using an additional 484 individuals with prevalent late AMD. GWAS meta-analysis confirmed previously reported association of variants at the complement factor H (CFH) (peak P = 1.5{\texttimes}10(-31)) and age-related maculopathy susceptibility 2 (ARMS2) (P = 4.3{\texttimes}10(-24)) loci, and suggested Apolipoprotein E (ApoE) polymorphisms (rs2075650; P = 1.1{\texttimes}10(-6)) associated with early AMD. Other possible loci that did not reach GWAS significance included variants in the zinc finger protein gene GLI3 (rs2049622; P = 8.9{\texttimes}10(-6)) and upstream of GLI2 (rs6721654; P = 6.5{\texttimes}10(-6)), encoding retinal Sonic hedgehog signalling regulators, and in the tyrosinase (TYR) gene (rs621313; P = 3.5{\texttimes}10(-6)), involved in melanin biosynthesis. For a range of published, late AMD risk loci, estimated effect sizes were significantly lower for early than late AMD. This study confirms the involvement of multiple established AMD risk variants in early AMD, but suggests weaker genetic effects on the risk of early AMD relative to late AMD. Several biological processes were suggested to be potentially specific for early AMD, including pathways regulating RPE cell melanin content and signalling pathways potentially involved in retinal regeneration, generating hypotheses for further investigation.

}, keywords = {Apolipoproteins E, Complement Factor H, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Kruppel-Like Transcription Factors, Macular Degeneration, Nerve Tissue Proteins, Polymorphism, Single Nucleotide, Proteins, Risk Factors, Zinc Finger Protein Gli3}, issn = {1932-6203}, doi = {10.1371/journal.pone.0053830}, author = {Holliday, Elizabeth G and Smith, Albert V and Cornes, Belinda K and Buitendijk, Gabri{\"e}lle H S and Jensen, Richard A and Sim, Xueling and Aspelund, Thor and Aung, Tin and Baird, Paul N and Boerwinkle, Eric and Cheng, Ching Yu and van Duijn, Cornelia M and Eiriksdottir, Gudny and Gudnason, Vilmundur and Harris, Tamara and Hewitt, Alex W and Inouye, Michael and Jonasson, Fridbert and Klein, Barbara E K and Launer, Lenore and Li, Xiaohui and Liew, Gerald and Lumley, Thomas and McElduff, Patrick and McKnight, Barbara and Mitchell, Paul and Psaty, Bruce M and Rochtchina, Elena and Rotter, Jerome I and Scott, Rodney J and Tay, Wanting and Taylor, Kent and Teo, Yik Ying and Uitterlinden, Andr{\'e} G and Viswanathan, Ananth and Xie, Sophia and Vingerling, Johannes R and Klaver, Caroline C W and Tai, E Shyong and Siscovick, David and Klein, Ronald and Cotch, Mary Frances and Wong, Tien Y and Attia, John and Wang, Jie Jin} } @article {7686, title = {A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure.}, journal = {Am J Hum Genet}, volume = {102}, year = {2018}, month = {2018 Mar 01}, pages = {375-400}, abstract = {

Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined \~{}18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5~{\texttimes} 10) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5~{\texttimes} 10). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2).

}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2018.01.015}, author = {Sung, Yun J and Winkler, Thomas W and de Las Fuentes, Lisa and Bentley, Amy R and Brown, Michael R and Kraja, Aldi T and Schwander, Karen and Ntalla, Ioanna and Guo, Xiuqing and Franceschini, Nora and Lu, Yingchang and Cheng, Ching-Yu and Sim, Xueling and Vojinovic, Dina and Marten, Jonathan and Musani, Solomon K and Li, Changwei and Feitosa, Mary F and Kilpel{\"a}inen, Tuomas O and Richard, Melissa A and Noordam, Raymond and Aslibekyan, Stella and Aschard, Hugues and Bartz, Traci M and Dorajoo, Rajkumar and Liu, Yongmei and Manning, Alisa K and Rankinen, Tuomo and Smith, Albert Vernon and Tajuddin, Salman M and Tayo, Bamidele O and Warren, Helen R and Zhao, Wei and Zhou, Yanhua and Matoba, Nana and Sofer, Tamar and Alver, Maris and Amini, Marzyeh and Boissel, Mathilde and Chai, Jin Fang and Chen, Xu and Divers, Jasmin and Gandin, Ilaria and Gao, Chuan and Giulianini, Franco and Goel, Anuj and Harris, Sarah E and Hartwig, Fernando Pires and Horimoto, Andrea R V R and Hsu, Fang-Chi and Jackson, Anne U and K{\"a}h{\"o}nen, Mika and Kasturiratne, Anuradhani and Kuhnel, Brigitte and Leander, Karin and Lee, Wen-Jane and Lin, Keng-Hung and {\textquoteright}an Luan, Jian and McKenzie, Colin A and Meian, He and Nelson, Christopher P and Rauramaa, Rainer and Schupf, Nicole and Scott, Robert A and Sheu, Wayne H H and Stan{\v c}{\'a}kov{\'a}, Alena and Takeuchi, Fumihiko and van der Most, Peter J and Varga, Tibor V and Wang, Heming and Wang, Yajuan and Ware, Erin B and Weiss, Stefan and Wen, Wanqing and Yanek, Lisa R and Zhang, Weihua and Zhao, Jing Hua and Afaq, Saima and Alfred, Tamuno and Amin, Najaf and Arking, Dan and Aung, Tin and Barr, R Graham and Bielak, Lawrence F and Boerwinkle, Eric and Bottinger, Erwin P and Braund, Peter S and Brody, Jennifer A and Broeckel, Ulrich and Cabrera, Claudia P and Cade, Brian and Caizheng, Yu and Campbell, Archie and Canouil, Micka{\"e}l and Chakravarti, Aravinda and Chauhan, Ganesh and Christensen, Kaare and Cocca, Massimiliano and Collins, Francis S and Connell, John M and de Mutsert, Ren{\'e}e and de Silva, H Janaka and Debette, Stephanie and D{\"o}rr, Marcus and Duan, Qing and Eaton, Charles B and Ehret, Georg and Evangelou, Evangelos and Faul, Jessica D and Fisher, Virginia A and Forouhi, Nita G and Franco, Oscar H and Friedlander, Yechiel and Gao, He and Gigante, Bruna and Graff, Misa and Gu, C Charles and Gu, Dongfeng and Gupta, Preeti and Hagenaars, Saskia P and Harris, Tamara B and He, Jiang and Heikkinen, Sami and Heng, Chew-Kiat and Hirata, Makoto and Hofman, Albert and Howard, Barbara V and Hunt, Steven and Irvin, Marguerite R and Jia, Yucheng and Joehanes, Roby and Justice, Anne E and Katsuya, Tomohiro and Kaufman, Joel and Kerrison, Nicola D and Khor, Chiea Chuen and Koh, Woon-Puay and Koistinen, Heikki A and Komulainen, Pirjo and Kooperberg, Charles and Krieger, Jose E and Kubo, Michiaki and Kuusisto, Johanna and Langefeld, Carl D and Langenberg, Claudia and Launer, Lenore J and Lehne, Benjamin and Lewis, Cora E and Li, Yize and Lim, Sing Hui and Lin, Shiow and Liu, Ching-Ti and Liu, Jianjun and Liu, Jingmin and Liu, Kiang and Liu, Yeheng and Loh, Marie and Lohman, Kurt K and Long, Jirong and Louie, Tin and M{\"a}gi, Reedik and Mahajan, Anubha and Meitinger, Thomas and Metspalu, Andres and Milani, Lili and Momozawa, Yukihide and Morris, Andrew P and Mosley, Thomas H and Munson, Peter and Murray, Alison D and Nalls, Mike A and Nasri, Ubaydah and Norris, Jill M and North, Kari and Ogunniyi, Adesola and Padmanabhan, Sandosh and Palmas, Walter R and Palmer, Nicholette D and Pankow, James S and Pedersen, Nancy L and Peters, Annette and Peyser, Patricia A and Polasek, Ozren and Raitakari, Olli T and Renstrom, Frida and Rice, Treva K and Ridker, Paul M and Robino, Antonietta and Robinson, Jennifer G and Rose, Lynda M and Rudan, Igor and Sabanayagam, Charumathi and Salako, Babatunde L and Sandow, Kevin and Schmidt, Carsten O and Schreiner, Pamela J and Scott, William R and Seshadri, Sudha and Sever, Peter and Sitlani, Colleen M and Smith, Jennifer A and Snieder, Harold and Starr, John M and Strauch, Konstantin and Tang, Hua and Taylor, Kent D and Teo, Yik Ying and Tham, Yih Chung and Uitterlinden, Andr{\'e} G and Waldenberger, Melanie and Wang, Lihua and Wang, Ya X and Wei, Wen Bin and Williams, Christine and Wilson, Gregory and Wojczynski, Mary K and Yao, Jie and Yuan, Jian-Min and Zonderman, Alan B and Becker, Diane M and Boehnke, Michael and Bowden, Donald W and Chambers, John C and Chen, Yii-Der Ida and de Faire, Ulf and Deary, Ian J and Esko, T{\~o}nu and Farrall, Martin and Forrester, Terrence and Franks, Paul W and Freedman, Barry I and Froguel, Philippe and Gasparini, Paolo and Gieger, Christian and Horta, Bernardo Lessa and Hung, Yi-Jen and Jonas, Jost B and Kato, Norihiro and Kooner, Jaspal S and Laakso, Markku and Lehtim{\"a}ki, Terho and Liang, Kae-Woei and Magnusson, Patrik K E and Newman, Anne B and Oldehinkel, Albertine J and Pereira, Alexandre C and Redline, Susan and Rettig, Rainer and Samani, Nilesh J and Scott, James and Shu, Xiao-Ou and van der Harst, Pim and Wagenknecht, Lynne E and Wareham, Nicholas J and Watkins, Hugh and Weir, David R and Wickremasinghe, Ananda R and Wu, Tangchun and Zheng, Wei and Kamatani, Yoichiro and Laurie, Cathy C and Bouchard, Claude and Cooper, Richard S and Evans, Michele K and Gudnason, Vilmundur and Kardia, Sharon L R and Kritchevsky, Stephen B and Levy, Daniel and O{\textquoteright}Connell, Jeff R and Psaty, Bruce M and van Dam, Rob M and Sims, Mario and Arnett, Donna K and Mook-Kanamori, Dennis O and Kelly, Tanika N and Fox, Ervin R and Hayward, Caroline and Fornage, Myriam and Rotimi, Charles N and Province, Michael A and van Duijn, Cornelia M and Tai, E Shyong and Wong, Tien Yin and Loos, Ruth J F and Reiner, Alex P and Rotter, Jerome I and Zhu, Xiaofeng and Bierut, Laura J and Gauderman, W James and Caulfield, Mark J and Elliott, Paul and Rice, Kenneth and Munroe, Patricia B and Morrison, Alanna C and Cupples, L Adrienne and Rao, Dabeeru C and Chasman, Daniel I} } @article {7792, title = {Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.}, journal = {PLoS One}, volume = {13}, year = {2018}, month = {2018}, pages = {e0198166}, abstract = {

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0198166}, author = {Feitosa, Mary F and Kraja, Aldi T and Chasman, Daniel I and Sung, Yun J and Winkler, Thomas W and Ntalla, Ioanna and Guo, Xiuqing and Franceschini, Nora and Cheng, Ching-Yu and Sim, Xueling and Vojinovic, Dina and Marten, Jonathan and Musani, Solomon K and Li, Changwei and Bentley, Amy R and Brown, Michael R and Schwander, Karen and Richard, Melissa A and Noordam, Raymond and Aschard, Hugues and Bartz, Traci M and Bielak, Lawrence F and Dorajoo, Rajkumar and Fisher, Virginia and Hartwig, Fernando P and Horimoto, Andrea R V R and Lohman, Kurt K and Manning, Alisa K and Rankinen, Tuomo and Smith, Albert V and Tajuddin, Salman M and Wojczynski, Mary K and Alver, Maris and Boissel, Mathilde and Cai, Qiuyin and Campbell, Archie and Chai, Jin Fang and Chen, Xu and Divers, Jasmin and Gao, Chuan and Goel, Anuj and Hagemeijer, Yanick and Harris, Sarah E and He, Meian and Hsu, Fang-Chi and Jackson, Anne U and K{\"a}h{\"o}nen, Mika and Kasturiratne, Anuradhani and Komulainen, Pirjo and Kuhnel, Brigitte and Laguzzi, Federica and Luan, Jian{\textquoteright}an and Matoba, Nana and Nolte, Ilja M and Padmanabhan, Sandosh and Riaz, Muhammad and Rueedi, Rico and Robino, Antonietta and Said, M Abdullah and Scott, Robert A and Sofer, Tamar and Stan{\v c}{\'a}kov{\'a}, Alena and Takeuchi, Fumihiko and Tayo, Bamidele O and van der Most, Peter J and Varga, Tibor V and Vitart, Veronique and Wang, Yajuan and Ware, Erin B and Warren, Helen R and Weiss, Stefan and Wen, Wanqing and Yanek, Lisa R and Zhang, Weihua and Zhao, Jing Hua and Afaq, Saima and Amin, Najaf and Amini, Marzyeh and Arking, Dan E and Aung, Tin and Boerwinkle, Eric and Borecki, Ingrid and Broeckel, Ulrich and Brown, Morris and Brumat, Marco and Burke, Gregory L and Canouil, Micka{\"e}l and Chakravarti, Aravinda and Charumathi, Sabanayagam and Ida Chen, Yii-Der and Connell, John M and Correa, Adolfo and de Las Fuentes, Lisa and de Mutsert, Ren{\'e}e and de Silva, H Janaka and Deng, Xuan and Ding, Jingzhong and Duan, Qing and Eaton, Charles B and Ehret, Georg and Eppinga, Ruben N and Evangelou, Evangelos and Faul, Jessica D and Felix, Stephan B and Forouhi, Nita G and Forrester, Terrence and Franco, Oscar H and Friedlander, Yechiel and Gandin, Ilaria and Gao, He and Ghanbari, Mohsen and Gigante, Bruna and Gu, C Charles and Gu, Dongfeng and Hagenaars, Saskia P and Hallmans, G{\"o}ran and Harris, Tamara B and He, Jiang and Heikkinen, Sami and Heng, Chew-Kiat and Hirata, Makoto and Howard, Barbara V and Ikram, M Arfan and John, Ulrich and Katsuya, Tomohiro and Khor, Chiea Chuen and Kilpel{\"a}inen, Tuomas O and Koh, Woon-Puay and Krieger, Jose E and Kritchevsky, Stephen B and Kubo, Michiaki and Kuusisto, Johanna and Lakka, Timo A and Langefeld, Carl D and Langenberg, Claudia and Launer, Lenore J and Lehne, Benjamin and Lewis, Cora E and Li, Yize and Lin, Shiow and Liu, Jianjun and Liu, Jingmin and Loh, Marie and Louie, Tin and M{\"a}gi, Reedik and McKenzie, Colin A and Meitinger, Thomas and Metspalu, Andres and Milaneschi, Yuri and Milani, Lili and Mohlke, Karen L and Momozawa, Yukihide and Nalls, Mike A and Nelson, Christopher P and Sotoodehnia, Nona and Norris, Jill M and O{\textquoteright}Connell, Jeff R and Palmer, Nicholette D and Perls, Thomas and Pedersen, Nancy L and Peters, Annette and Peyser, Patricia A and Poulter, Neil and Raffel, Leslie J and Raitakari, Olli T and Roll, Kathryn and Rose, Lynda M and Rosendaal, Frits R and Rotter, Jerome I and Schmidt, Carsten O and Schreiner, Pamela J and Schupf, Nicole and Scott, William R and Sever, Peter S and Shi, Yuan and Sidney, Stephen and Sims, Mario and Sitlani, Colleen M and Smith, Jennifer A and Snieder, Harold and Starr, John M and Strauch, Konstantin and Stringham, Heather M and Tan, Nicholas Y Q and Tang, Hua and Taylor, Kent D and Teo, Yik Ying and Tham, Yih Chung and Turner, Stephen T and Uitterlinden, Andr{\'e} G and Vollenweider, Peter and Waldenberger, Melanie and Wang, Lihua and Wang, Ya Xing and Wei, Wen Bin and Williams, Christine 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 Chambers, John C and Deary, Ian J and Esko, T{\~o}nu and Farrall, Martin and Franks, Paul W and Freedman, Barry I and Froguel, Philippe and Gasparini, Paolo and Gieger, Christian and Jonas, Jost Bruno and Kamatani, Yoichiro and Kato, Norihiro and Kooner, Jaspal S and Kutalik, Zolt{\'a}n and Laakso, Markku and Laurie, Cathy C and Leander, Karin and Lehtim{\"a}ki, Terho and Study, Lifelines Cohort and Magnusson, Patrik K E and Oldehinkel, Albertine J and Penninx, Brenda W J H and Polasek, Ozren and Porteous, David J and Rauramaa, Rainer and Samani, Nilesh J and Scott, James and Shu, Xiao-Ou and van der Harst, Pim and Wagenknecht, Lynne E and Wareham, Nicholas J and Watkins, Hugh and Weir, David R and Wickremasinghe, Ananda R and Wu, Tangchun and Zheng, Wei and Bouchard, Claude and Christensen, Kaare and Evans, Michele K and Gudnason, Vilmundur and Horta, Bernardo L and Kardia, Sharon L R and Liu, Yongmei and Pereira, Alexandre C and Psaty, Bruce M and Ridker, Paul M and van Dam, Rob M and Gauderman, W James and Zhu, Xiaofeng and Mook-Kanamori, Dennis O and Fornage, Myriam and Rotimi, Charles N and Cupples, L Adrienne and Kelly, Tanika N and Fox, Ervin R and Hayward, Caroline and van Duijn, Cornelia M and Tai, E Shyong and Wong, Tien Yin and Kooperberg, Charles and Palmas, Walter and Rice, Kenneth and Morrison, Alanna C and Elliott, Paul and Caulfield, Mark J and Munroe, Patricia B and Rao, Dabeeru C and Province, Michael A and Levy, Daniel} } @article {7970, title = {Multi-Ancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.}, journal = {Am J Epidemiol}, year = {2019}, month = {2019 Jan 29}, abstract = {

An individual{\textquoteright}s lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multi-ancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in Stage 1 (genome-wide discovery) and 66 studies in Stage 2 (focused follow-up), for a total of 394,584 individuals from five ancestry groups. Genetic main and interaction effects were jointly assessed by a 2 degrees of freedom (DF) test, and a 1 DF test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P~<~1~{\texttimes}~10-6) with lipid levels in Stage 1 and were evaluated in Stage 2, followed by combined analyses of Stage 1 and Stage 2. In the combined analysis of Stage 1 and Stage 2, 147 independent loci were associated with lipid levels at P~<~5~{\texttimes}~10-8 using 2 DF tests, of which 18 were novel. No genome-wide significant associations were found testing the interaction effect alone. The novel loci included several genes (PCSK5, VEGFB, and A1CF) with a putative role in lipid metabolism based on existing evidence from cellular and experimental models.

}, issn = {1476-6256}, doi = {10.1093/aje/kwz005}, author = {de Vries, Paul S and Brown, Michael R and Bentley, Amy R and Sung, Yun J and Winkler, Thomas W and Ntalla, Ioanna and Schwander, Karen and Kraja, Aldi T and Guo, Xiuqing and Franceschini, Nora and Cheng, Ching-Yu and Sim, Xueling and Vojinovic, Dina and Huffman, Jennifer E and Musani, Solomon K and Li, Changwei and Feitosa, Mary F and Richard, Melissa A and Noordam, Raymond and Aschard, Hugues and Bartz, Traci M and Bielak, Lawrence F and Deng, Xuan and Dorajoo, Rajkumar and Lohman, Kurt K and Manning, Alisa K and Rankinen, Tuomo and Smith, Albert V and Tajuddin, Salman M and Evangelou, Evangelos and Graff, Mariaelisa and Alver, Maris and Boissel, Mathilde and Chai, Jin Fang and Chen, Xu and Divers, Jasmin and Gandin, Ilaria and Gao, Chuan and Goel, Anuj and Hagemeijer, Yanick and Harris, Sarah E and Hartwig, Fernando P and He, Meian and Horimoto, Andrea R V R and Hsu, Fang-Chi and Jackson, Anne U and Kasturiratne, Anuradhani and Komulainen, Pirjo and Kuhnel, Brigitte and Laguzzi, Federica and Lee, Joseph H and Luan, Jian{\textquoteright}an and Lyytik{\"a}inen, Leo-Pekka and Matoba, Nana and Nolte, Ilja M and Pietzner, Maik and Riaz, Muhammad and Said, M Abdullah and Scott, Robert A and Sofer, Tamar and Stan{\v c}{\'a}kov{\'a}, Alena and Takeuchi, Fumihiko and Tayo, Bamidele O and van der Most, Peter J and Varga, Tibor V and Wang, Yajuan and Ware, Erin B and Wen, Wanqing and Yanek, Lisa R and Zhang, Weihua and Zhao, Jing Hua and Afaq, Saima and Amin, Najaf and Amini, Marzyeh and Arking, Dan E and Aung, Tin and Ballantyne, Christie and Boerwinkle, Eric and Broeckel, Ulrich and Campbell, Archie and Canouil, Micka{\"e}l and Charumathi, Sabanayagam and Chen, Yii-Der Ida and Connell, John M and de Faire, Ulf and de Las Fuentes, Lisa and de Mutsert, Ren{\'e}e and de Silva, H Janaka and Ding, Jingzhong and Dominiczak, Anna F and Duan, Qing and Eaton, Charles B and Eppinga, Ruben N and Faul, Jessica D and Fisher, Virginia and Forrester, Terrence and Franco, Oscar H and Friedlander, Yechiel and Ghanbari, Mohsen and Giulianini, Franco and Grabe, Hans J and Grove, Megan L and Gu, C Charles and Harris, Tamara B and Heikkinen, Sami and Heng, Chew-Kiat and Hirata, Makoto and Hixson, James E and Howard, Barbara V and Ikram, M Arfan and Jacobs, David R and Johnson, Craig and Jonas, Jost Bruno and Kammerer, Candace M and Katsuya, Tomohiro and Khor, Chiea Chuen and Kilpel{\"a}inen, Tuomas O and Koh, Woon-Puay and Koistinen, Heikki A and Kolcic, Ivana and Kooperberg, Charles and Krieger, Jose E and Kritchevsky, Steve B and Kubo, Michiaki and Kuusisto, Johanna and Lakka, Timo A and Langefeld, Carl D and Langenberg, Claudia and Launer, Lenore J and Lehne, Benjamin and Lemaitre, Rozenn N and Li, Yize and Liang, Jingjing and Liu, Jianjun and Liu, Kiang and Loh, Marie and Louie, Tin and M{\"a}gi, Reedik and Manichaikul, Ani W and McKenzie, Colin A and Meitinger, Thomas and Metspalu, Andres and Milaneschi, Yuri and Milani, Lili and Mohlke, Karen L and Mosley, Thomas H and Mukamal, Kenneth J and Nalls, Mike A and Nauck, Matthias and Nelson, Christopher P and Sotoodehnia, Nona and O{\textquoteright}Connell, Jeff R and Palmer, Nicholette D and Pazoki, Raha and Pedersen, Nancy L and Peters, Annette and Peyser, Patricia A and Polasek, Ozren and Poulter, Neil and Raffel, Leslie J and Raitakari, Olli T and Reiner, Alex P and Rice, Treva K and Rich, Stephen S and Robino, Antonietta and Robinson, Jennifer G and Rose, Lynda M and Rudan, Igor and Schmidt, Carsten O and Schreiner, Pamela J and Scott, William R and Sever, Peter and Shi, Yuan and Sidney, Stephen and Sims, Mario and Smith, Blair H and Smith, Jennifer A and Snieder, Harold and Starr, John M and Strauch, Konstantin and Tan, Nicholas and Taylor, Kent D and Teo, Yik Ying and Tham, Yih Chung and Uitterlinden, Andr{\'e} G and van Heemst, Diana and Vuckovic, Dragana and Waldenberger, Melanie and Wang, Lihua and Wang, Yujie and Wang, Zhe and Wei, Wen Bin and Williams, Christine and Wilson, Gregory and Wojczynski, Mary K and Yao, Jie and Yu, Bing 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 Chambers, John C and Deary, Ian J and Esko, T{\~o}nu and Farrall, Martin and Franks, Paul W and Freedman, Barry I and Froguel, Philippe and Gasparini, Paolo and Gieger, Christian and Horta, Bernardo L and Kamatani, Yoichiro and Kato, Norihiro and Kooner, Jaspal S and Laakso, Markku and Leander, Karin and Lehtim{\"a}ki, Terho and Magnusson, Patrik K E and Penninx, Brenda and Pereira, Alexandre C and Rauramaa, Rainer and Samani, Nilesh J and Scott, James and Shu, Xiao-Ou and van der Harst, Pim and Wagenknecht, Lynne E and Wang, Ya Xing and Wareham, Nicholas J and Watkins, Hugh and Weir, David R and Wickremasinghe, Ananda R and Zheng, Wei and Elliott, Paul and North, Kari E and Bouchard, Claude and Evans, Michele K and Gudnason, Vilmundur and Liu, Ching-Ti and Liu, Yongmei and Psaty, Bruce M and Ridker, Paul M and van Dam, Rob M and Kardia, Sharon L R and Zhu, Xiaofeng and Rotimi, Charles N and Mook-Kanamori, Dennis O and Fornage, Myriam and Kelly, Tanika N and Fox, Ervin R and Hayward, Caroline and van Duijn, Cornelia M and Tai, E Shyong and Wong, Tien Yin and Liu, Jingmin and Rotter, Jerome I and Gauderman, W James and Province, Michael A and Munroe, Patricia B and Rice, Kenneth and Chasman, Daniel I and Cupples, L Adrienne and Rao, Dabeeru C and Morrison, Alanna C} } @article {8005, title = {Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids.}, journal = {Nat Genet}, volume = {51}, year = {2019}, month = {2019 Apr}, pages = {636-648}, abstract = {

The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.

}, issn = {1546-1718}, doi = {10.1038/s41588-019-0378-y}, author = {Bentley, Amy R and Sung, Yun J and Brown, Michael R and Winkler, Thomas W and Kraja, Aldi T and Ntalla, Ioanna and Schwander, Karen and Chasman, Daniel I and Lim, Elise and Deng, Xuan and Guo, Xiuqing and Liu, Jingmin and Lu, Yingchang and Cheng, Ching-Yu and Sim, Xueling and Vojinovic, Dina and Huffman, Jennifer E and Musani, Solomon K and Li, Changwei and Feitosa, Mary F and Richard, Melissa A and Noordam, Raymond and Baker, Jenna and Chen, Guanjie and Aschard, Hugues and Bartz, Traci M and Ding, Jingzhong and Dorajoo, Rajkumar and Manning, Alisa K and Rankinen, Tuomo and Smith, Albert V and Tajuddin, Salman M and Zhao, Wei and Graff, Mariaelisa and Alver, Maris and Boissel, Mathilde and Chai, Jin Fang and Chen, Xu and Divers, Jasmin and Evangelou, Evangelos and Gao, Chuan and Goel, Anuj and Hagemeijer, Yanick and Harris, Sarah E and Hartwig, Fernando P and He, Meian and Horimoto, Andrea R V R and Hsu, Fang-Chi and Hung, Yi-Jen and Jackson, Anne U and Kasturiratne, Anuradhani and Komulainen, Pirjo and Kuhnel, Brigitte and Leander, Karin and Lin, Keng-Hung and Luan, Jian{\textquoteright}an and Lyytik{\"a}inen, Leo-Pekka and Matoba, Nana and Nolte, Ilja M and Pietzner, Maik and Prins, Bram and Riaz, Muhammad and Robino, Antonietta and Said, M Abdullah and Schupf, Nicole and Scott, Robert A and Sofer, Tamar and Stan{\v c}{\'a}kov{\'a}, Alena and Takeuchi, Fumihiko and Tayo, Bamidele O and van der Most, Peter J and Varga, Tibor V and Wang, Tzung-Dau and Wang, Yajuan and Ware, Erin B and Wen, Wanqing and Xiang, Yong-Bing and Yanek, Lisa R and Zhang, Weihua and Zhao, Jing Hua and Adeyemo, Adebowale and Afaq, Saima and Amin, Najaf and Amini, Marzyeh and Arking, Dan E and Arzumanyan, Zorayr and Aung, Tin and Ballantyne, Christie and Barr, R Graham and Bielak, Lawrence F and Boerwinkle, Eric and Bottinger, Erwin P and Broeckel, Ulrich and Brown, Morris and Cade, Brian E and Campbell, Archie and Canouil, Micka{\"e}l and Charumathi, Sabanayagam and Chen, Yii-Der Ida and Christensen, Kaare and Concas, Maria Pina and Connell, John M and de Las Fuentes, Lisa and de Silva, H Janaka and de Vries, Paul S and Doumatey, Ayo and Duan, Qing and Eaton, Charles B and Eppinga, Ruben N and Faul, Jessica D and Floyd, James S and Forouhi, Nita G and Forrester, Terrence and Friedlander, Yechiel and Gandin, Ilaria and Gao, He and Ghanbari, Mohsen and Gharib, Sina A and Gigante, Bruna and Giulianini, Franco and Grabe, Hans J and Gu, C Charles and Harris, Tamara B and Heikkinen, Sami and Heng, Chew-Kiat and Hirata, Makoto and Hixson, James E and Ikram, M Arfan and Jia, Yucheng and Joehanes, Roby and Johnson, Craig and Jonas, Jost Bruno and Justice, Anne E and Katsuya, Tomohiro and Khor, Chiea Chuen and Kilpel{\"a}inen, Tuomas O and Koh, Woon-Puay and Kolcic, Ivana and Kooperberg, Charles and Krieger, Jose E and Kritchevsky, Stephen B and Kubo, Michiaki and Kuusisto, Johanna and Lakka, Timo A and Langefeld, Carl D and Langenberg, Claudia and Launer, Lenore J and Lehne, Benjamin and Lewis, Cora E and Li, Yize and Liang, Jingjing and Lin, Shiow and Liu, Ching-Ti and Liu, Jianjun and Liu, Kiang and Loh, Marie and Lohman, Kurt K and Louie, Tin and Luzzi, Anna and M{\"a}gi, Reedik and Mahajan, Anubha and Manichaikul, Ani W and McKenzie, Colin A and Meitinger, Thomas and Metspalu, Andres and Milaneschi, Yuri and Milani, Lili and Mohlke, Karen L and Momozawa, Yukihide and Morris, Andrew P and Murray, Alison D and Nalls, Mike A and Nauck, Matthias and Nelson, Christopher P and North, Kari E and O{\textquoteright}Connell, Jeffrey R and Palmer, Nicholette D and Papanicolau, George J and Pedersen, Nancy L and Peters, Annette and Peyser, Patricia A and Polasek, Ozren and Poulter, Neil and Raitakari, Olli T and Reiner, Alex P and Renstrom, Frida and Rice, Treva K and Rich, Stephen S and Robinson, Jennifer G and Rose, Lynda M and Rosendaal, Frits R and Rudan, Igor and Schmidt, Carsten O and Schreiner, Pamela J and Scott, William R and Sever, Peter and Shi, Yuan and Sidney, Stephen and Sims, Mario and Smith, Jennifer A and Snieder, Harold and Starr, John M and Strauch, Konstantin and Stringham, Heather M and Tan, Nicholas Y Q and Tang, Hua and Taylor, Kent D and Teo, Yik Ying and Tham, Yih Chung and Tiemeier, Henning and Turner, Stephen T and Uitterlinden, Andr{\'e} G and van Heemst, Diana and Waldenberger, Melanie and Wang, Heming and Wang, Lan and Wang, Lihua and Wei, Wen Bin and Williams, Christine A and Wilson, Gregory and Wojczynski, Mary K and Yao, Jie and Young, Kristin and Yu, Caizheng and Yuan, Jian-Min and Zhou, Jie and Zonderman, Alan B and Becker, Diane M and Boehnke, Michael and Bowden, Donald W and Chambers, John C and Cooper, Richard S and de Faire, Ulf and Deary, Ian J and Elliott, Paul and Esko, T{\~o}nu and Farrall, Martin and Franks, Paul W and Freedman, Barry I and Froguel, Philippe and Gasparini, Paolo and Gieger, Christian and Horta, Bernardo L and Juang, Jyh-Ming Jimmy and Kamatani, Yoichiro and Kammerer, Candace M and Kato, Norihiro and Kooner, Jaspal S and Laakso, Markku and Laurie, Cathy C and Lee, I-Te and Lehtim{\"a}ki, Terho and Magnusson, Patrik K E and Oldehinkel, Albertine J and Penninx, Brenda W J H and Pereira, Alexandre C and Rauramaa, Rainer and Redline, Susan and Samani, Nilesh J and Scott, James and Shu, Xiao-Ou and van der Harst, Pim and Wagenknecht, Lynne E and Wang, Jun-Sing and Wang, Ya Xing and Wareham, Nicholas J and Watkins, Hugh and Weir, David R and Wickremasinghe, Ananda R and Wu, Tangchun and Zeggini, Eleftheria and Zheng, Wei and Bouchard, Claude and Evans, Michele K and Gudnason, Vilmundur and Kardia, Sharon L R and Liu, Yongmei and Psaty, Bruce M and Ridker, Paul M and van Dam, Rob M and Mook-Kanamori, Dennis O and Fornage, Myriam and Province, Michael A and Kelly, Tanika N and Fox, Ervin R and Hayward, Caroline and van Duijn, Cornelia M and Tai, E Shyong and Wong, Tien Yin and Loos, Ruth J F and Franceschini, Nora and Rotter, Jerome I and Zhu, Xiaofeng and Bierut, Laura J and Gauderman, W James and Rice, Kenneth and Munroe, Patricia B and Morrison, Alanna C and Rao, Dabeeru C and Rotimi, Charles N and Cupples, L Adrienne} } @article {8774, title = {Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes.}, journal = {Nat Commun}, volume = {12}, year = {2021}, month = {2021 06 09}, pages = {3505}, abstract = {

Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1\% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60\% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias.

}, keywords = {Adult, Biological Variation, Population, Biomarkers, Diabetes Mellitus, Type 2, Dyslipidemias, Exome, Genetic Predisposition to Disease, Genotype, Humans, Multifactorial Inheritance, Penetrance, Risk Assessment}, issn = {2041-1723}, doi = {10.1038/s41467-021-23556-4}, author = {Goodrich, Julia K and Singer-Berk, Moriel and Son, Rachel and Sveden, Abigail and Wood, Jordan and England, Eleina and Cole, Joanne B and Weisburd, Ben and Watts, Nick and Caulkins, Lizz and Dornbos, Peter and Koesterer, Ryan and Zappala, Zachary and Zhang, Haichen and Maloney, Kristin A and Dahl, Andy and Aguilar-Salinas, Carlos A and Atzmon, Gil and Barajas-Olmos, Francisco and Barzilai, Nir and Blangero, John and Boerwinkle, Eric and Bonnycastle, Lori L and Bottinger, Erwin and Bowden, Donald W and Centeno-Cruz, Federico and Chambers, John C and Chami, Nathalie and Chan, Edmund and Chan, Juliana and Cheng, Ching-Yu and Cho, Yoon Shin and Contreras-Cubas, Cecilia and C{\'o}rdova, Emilio and Correa, Adolfo and DeFronzo, Ralph A and Duggirala, Ravindranath and Dupuis, Jos{\'e}e and Garay-Sevilla, Ma Eugenia and Garc{\'\i}a-Ortiz, Humberto and Gieger, Christian and Glaser, Benjamin and Gonz{\'a}lez-Villalpando, Clicerio and Gonzalez, Ma Elena and Grarup, Niels and Groop, Leif and Gross, Myron and Haiman, Christopher and Han, Sohee and Hanis, Craig L and Hansen, Torben and Heard-Costa, Nancy L and Henderson, Brian E and Hernandez, Juan Manuel Malacara and Hwang, Mi Yeong and Islas-Andrade, Sergio and J{\o}rgensen, Marit E and Kang, Hyun Min and Kim, Bong-Jo and Kim, Young Jin and Koistinen, Heikki A and Kooner, Jaspal Singh and Kuusisto, Johanna and Kwak, Soo-Heon and Laakso, Markku and Lange, Leslie and Lee, Jong-Young and Lee, Juyoung and Lehman, Donna M and Linneberg, Allan and Liu, Jianjun and Loos, Ruth J F and Lyssenko, Valeriya and Ma, Ronald C W and Mart{\'\i}nez-Hern{\'a}ndez, Ang{\'e}lica and Meigs, James B and Meitinger, Thomas and Mendoza-Caamal, Elvia and Mohlke, Karen L and Morris, Andrew D and Morrison, Alanna C and Ng, Maggie C Y and Nilsson, Peter M and O{\textquoteright}Donnell, Christopher J and Orozco, Lorena and Palmer, Colin N A and Park, Kyong Soo and Post, Wendy S and Pedersen, Oluf and Preuss, Michael and Psaty, Bruce M and Reiner, Alexander P and Revilla-Monsalve, Cristina and Rich, Stephen S and Rotter, Jerome I and Saleheen, Danish and Schurmann, Claudia and Sim, Xueling and Sladek, Rob and Small, Kerrin S and So, Wing Yee and Spector, Timothy D and Strauch, Konstantin and Strom, Tim M and Tai, E Shyong and Tam, Claudia H T and Teo, Yik Ying and Thameem, Farook and Tomlinson, Brian and Tracy, Russell P and Tuomi, Tiinamaija and Tuomilehto, Jaakko and Tusi{\'e}-Luna, Teresa and van Dam, Rob M and Vasan, Ramachandran S and Wilson, James G and Witte, Daniel R and Wong, Tien-Yin and Burtt, Noel P and Zaitlen, Noah and McCarthy, Mark I and Boehnke, Michael and Pollin, Toni I and Flannick, Jason and Mercader, Josep M and O{\textquoteright}Donnell-Luria, Anne and Baxter, Samantha and Florez, Jose C and MacArthur, Daniel G and Udler, Miriam S} } @article {8975, title = {Rare coding variants in 35 genes associate with circulating lipid levels-A multi-ancestry analysis of 170,000 exomes.}, journal = {Am J Hum Genet}, volume = {109}, year = {2022}, month = {2022 01 06}, pages = {81-96}, abstract = {

Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1\%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels; some of these genes have not been previously associated with lipid levels when using rare coding variation from population-based samples. We prioritize 32 genes in array-based genome-wide association study (GWAS) loci based on aggregations of rare coding variants; three (EVI5, SH2B3, and PLIN1) had no prior association of rare coding variants with lipid levels. Most of our associated genes showed evidence of association among multiple ancestries. Finally, we observed an enrichment of gene-based associations for low-density lipoprotein cholesterol drug target genes and for genes closest to GWAS index single-nucleotide polymorphisms (SNPs). Our results demonstrate that gene-based associations can be beneficial for drug target development and provide evidence that the gene closest to the array-based GWAS index SNP is often the functional gene for blood lipid levels.

}, keywords = {Alleles, Blood Glucose, Case-Control Studies, Computational Biology, Databases, Genetic, Diabetes Mellitus, Type 2, Exome, Genetic Predisposition to Disease, Genetic Variation, Genetics, Population, Genome-Wide Association Study, Humans, Lipid Metabolism, Lipids, Liver, Molecular Sequence Annotation, Multifactorial Inheritance, Open Reading Frames, Phenotype, Polymorphism, Single Nucleotide}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2021.11.021}, author = {Hindy, George and Dornbos, Peter and Chaffin, Mark D and Liu, Dajiang J and Wang, Minxian and Selvaraj, Margaret Sunitha and Zhang, David and Park, Joseph and Aguilar-Salinas, Carlos A and Antonacci-Fulton, Lucinda and Ardissino, Diego and Arnett, Donna K and Aslibekyan, Stella and Atzmon, Gil and Ballantyne, Christie M and Barajas-Olmos, Francisco and Barzilai, Nir and Becker, Lewis C and Bielak, Lawrence F and Bis, Joshua C and Blangero, John and Boerwinkle, Eric and Bonnycastle, Lori L and Bottinger, Erwin and Bowden, Donald W and Bown, Matthew J and Brody, Jennifer A and Broome, Jai G and Burtt, Noel P and Cade, Brian E and Centeno-Cruz, Federico and Chan, Edmund and Chang, Yi-Cheng and Chen, Yii-der I and Cheng, Ching-Yu and Choi, Won Jung and Chowdhury, Rajiv and Contreras-Cubas, Cecilia and C{\'o}rdova, Emilio J and Correa, Adolfo and Cupples, L Adrienne and Curran, Joanne E and Danesh, John and de Vries, Paul S and DeFronzo, Ralph A and Doddapaneni, Harsha and Duggirala, Ravindranath and Dutcher, Susan K and Ellinor, Patrick T and Emery, Leslie S and Florez, Jose C and Fornage, Myriam and Freedman, Barry I and Fuster, Valentin and Garay-Sevilla, Ma Eugenia and Garc{\'\i}a-Ortiz, Humberto and Germer, Soren and Gibbs, Richard A and Gieger, Christian and Glaser, Benjamin and Gonzalez, Clicerio and Gonzalez-Villalpando, Maria Elena and Graff, Mariaelisa and Graham, Sarah E and Grarup, Niels and Groop, Leif C and Guo, Xiuqing and Gupta, Namrata and Han, Sohee and Hanis, Craig L and Hansen, Torben and He, Jiang and Heard-Costa, Nancy L and Hung, Yi-Jen and Hwang, Mi Yeong and Irvin, Marguerite R and Islas-Andrade, Sergio and Jarvik, Gail P and Kang, Hyun Min and Kardia, Sharon L R and Kelly, Tanika and Kenny, Eimear E and Khan, Alyna T and Kim, Bong-Jo and Kim, Ryan W and Kim, Young Jin and Koistinen, Heikki A and Kooperberg, Charles and Kuusisto, Johanna and Kwak, Soo Heon and Laakso, Markku and Lange, Leslie A and Lee, Jiwon and Lee, Juyoung and Lee, Seonwook and Lehman, Donna M and Lemaitre, Rozenn N and Linneberg, Allan and Liu, Jianjun and Loos, Ruth J F and Lubitz, Steven A and Lyssenko, Valeriya and Ma, Ronald C W and Martin, Lisa Warsinger and Mart{\'\i}nez-Hern{\'a}ndez, Ang{\'e}lica and Mathias, Rasika A and McGarvey, Stephen T and McPherson, Ruth and Meigs, James B and Meitinger, Thomas and Melander, Olle and Mendoza-Caamal, Elvia and Metcalf, Ginger A and Mi, Xuenan and Mohlke, Karen L and Montasser, May E and Moon, Jee-Young and Moreno-Macias, Hortensia and Morrison, Alanna C and Muzny, Donna M and Nelson, Sarah C and Nilsson, Peter M and O{\textquoteright}Connell, Jeffrey R and Orho-Melander, Marju and Orozco, Lorena and Palmer, Colin N A and Palmer, Nicholette D and Park, Cheol Joo and Park, Kyong Soo and Pedersen, Oluf and Peralta, Juan M and Peyser, Patricia A and Post, Wendy S and Preuss, Michael and Psaty, Bruce M and Qi, Qibin and Rao, D C and Redline, Susan and Reiner, Alexander P and Revilla-Monsalve, Cristina and Rich, Stephen S and Samani, Nilesh and Schunkert, Heribert and Schurmann, Claudia and Seo, Daekwan and Seo, Jeong-Sun and Sim, Xueling and Sladek, Rob and Small, Kerrin S and So, Wing Yee and Stilp, Adrienne M and Tai, E Shyong and Tam, Claudia H T and Taylor, Kent D and Teo, Yik Ying and Thameem, Farook and Tomlinson, Brian and Tsai, Michael Y and Tuomi, Tiinamaija and Tuomilehto, Jaakko and Tusi{\'e}-Luna, Teresa and Udler, Miriam S and van Dam, Rob M and Vasan, Ramachandran S and Viaud Martinez, Karine A and Wang, Fei Fei and Wang, Xuzhi and Watkins, Hugh and Weeks, Daniel E and Wilson, James G and Witte, Daniel R and Wong, Tien-Yin and Yanek, Lisa R and Kathiresan, Sekar and Rader, Daniel J and Rotter, Jerome I and Boehnke, Michael and McCarthy, Mark I and Willer, Cristen J and Natarajan, Pradeep and Flannick, Jason A and Khera, Amit V and Peloso, Gina M} }