@article {12127, title = {Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.}, journal = {Mol Psychiatry}, volume = {26}, year = {2021}, pages = {2111-2125}, abstract = {

Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 {\texttimes} 10). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.

}, keywords = {Blood pressure, Epistasis, Genetic, Genetic Loci, Genome-Wide Association Study, Humans, Hypertension, Polymorphism, Single Nucleotide}, issn = {1476-5578}, doi = {10.1038/s41380-020-0719-3}, author = {de Las Fuentes, Lisa and Yun Ju Sung and Noordam, Raymond and Thomas W Winkler and Feitosa, Mary F and Schwander, Karen and Bentley, Amy R and Brown, Michael R and Guo, Xiuqing and Alisa Manning and Daniel I Chasman and Aschard, Hugues and Traci M Bartz and Bielak, Lawrence F and Campbell, Archie and Cheng, Ching-Yu and Dorajoo, Rajkumar and Hartwig, Fernando P and Horimoto, A R V R and Li, Changwei and Li-Gao, Ruifang and Liu, Yongmei and Marten, Jonathan and Musani, Solomon K and Ntalla, Ioanna and Rankinen, Tuomo and Melissa Richard and Sim, Xueling and Smith, Albert V and Tajuddin, Salman M and Bamidele O Tayo and Vojinovic, Dina and Warren, Helen R and Xuan, Deng and Alver, Maris and Boissel, Mathilde and Jin-Fang Chai and Chen, Xu and Christensen, Kaare and Divers, Jasmin and Evangelou, Evangelos and Gao, Chuan and Giorgia G Girotto and Sarah E Harris and He, Meian and Hsu, Fang-Chi and K{\"u}hnel, Brigitte and Laguzzi, Federica and Li, Xiaoyin and Lyytik{\"a}inen, Leo-Pekka and Ilja M Nolte and Poveda, Alaitz and Rauramaa, Rainer and Riaz, Muhammad and Rueedi, Rico and Shu, Xiao-Ou and Snieder, Harold and Sofer, Tamar and Takeuchi, Fumihiko and Verweij, Niek and Erin B Ware and Weiss, Stefan and Yanek, Lisa R and Amin, Najaf and Dan E Arking and Donna K Arnett and Bergmann, Sven and Boerwinkle, Eric and Brody, Jennifer A and Broeckel, Ulrich and Brumat, Marco and Burke, Gregory and Cabrera, Claudia P and Canouil, Micka{\"e}l and Chee, Miao Li and Chen, Yii-Der Ida and Cocca, Massimiliano and Connell, John and de Silva, H Janaka and de Vries, Paul S and Eiriksdottir, Gudny and Jessica Faul and Fisher, Virginia and Forrester, Terrence and Fox, Ervin F and Friedlander, Yechiel and Gao, He and Gigante, Bruna and Giulianini, Franco and Gu, Chi Charles and Gu, Dongfeng and Tamara B Harris and He, Jiang and Heikkinen, Sami and Heng, Chew-Kiat and Hunt, Steven and Ikram, M Arfan and Irvin, Marguerite R and K{\"a}h{\"o}nen, Mika and Kavousi, Maryam and Khor, Chiea Chuen and Kilpel{\"a}inen, Tuomas O and Koh, Woon-Puay and Komulainen, Pirjo and Kraja, Aldi T and Krieger, J E and Langefeld, Carl D and Li, Yize and Liang, Jingjing and David C Liewald and Liu, Ching-Ti and Liu, Jianjun and Kurt Lohman and M{\"a}gi, Reedik and McKenzie, Colin A and Meitinger, Thomas and Andres Metspalu and Milaneschi, Yuri and Lili Milani and Dennis O Mook-Kanamori and Michael A Nalls and Nelson, Christopher P and Norris, Jill M and Jeff O{\textquoteright}Connell and Ogunniyi, Adesola and Padmanabhan, Sandosh and Palmer, Nicholette D and Nancy L Pedersen and Thomas T Perls and Peters, Annette and Petersmann, Astrid and Peyser, Patricia A and Polasek, Ozren and David J Porteous and Raffel, Leslie J and Rice, Treva K and Rotter, Jerome I and Rudan, Igor and Rueda-Ochoa, Oscar-Leonel and Sabanayagam, Charumathi and Babatunde Salako and Schreiner, Pamela J and Shikany, James M and Stephen Sidney and Sims, Mario and Sitlani, Colleen M and Smith, Jennifer A and John M Starr and Strauch, Konstantin and Swertz, Morris A and Teumer, Alexander and Tham, Yih Chung and Andr{\'e} G Uitterlinden and Vaidya, Dhananjay and van der Ende, M Yldau and Waldenberger, Melanie and Wang, Lihua and Wang, Ya-Xing and Wei, Wen-Bin and David R Weir and Wen, Wanqing and Yao, Jie and Yu, Bing and Yu, Caizheng and Yuan, Jian-Min and Zhao, Wei and Alan B Zonderman and Becker, Diane M and Bowden, Donald W and Ian J Deary and D{\"o}rr, Marcus and T{\~o}nu Esko and Freedman, Barry I and Froguel, Philippe and Paolo P. Gasparini and Gieger, Christian and Jost Bruno Jonas and Kammerer, Candace M and Kato, Norihiro and Lakka, Timo A and Leander, Karin and Lehtim{\"a}ki, Terho and Patrik K E Magnusson and Marques-Vidal, Pedro and Brenda W J H Penninx and Nilesh J Samani and van der Harst, Pim and Wagenknecht, Lynne E and Wu, Tangchun and Zheng, Wei and Zhu, Xiaofeng and Bouchard, Claude and Cooper, Richard S and Correa, Adolfo and Michele K Evans and Gudnason, Vilmundur and Caroline Hayward and Horta, Bernardo L and Tanika N Kelly and Stephen B Kritchevsky and Levy, Daniel and Walter R Palmas and Pereira, A C and Province, Michael M and Psaty, Bruce M and Ridker, Paul M and Charles N Rotimi and Tai, E Shyong and van Dam, Rob M and Cornelia M van Duijn and Wong, Tien Yin and Kenneth Rice and Gauderman, W James and Alanna C Morrison and Kari E North and Sharon L R Kardia and Caulfield, Mark J and Elliott, Paul and Munroe, Patricia B and Franks, Paul W and Rao, Dabeeru C and Myriam Fornage} } @article {10225, title = {A meta-analysis of genome-wide association studies identifies multiple longevity genes.}, journal = {Nature Communications}, volume = {10}, year = {2019}, month = {08/2019}, pages = {3669}, abstract = {

Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.

}, keywords = {genes, Genome-Wide Association Study, GWA, longevity genes, meta-analysis}, issn = {2041-1723}, doi = {10.1038/s41467-019-11558-2}, url = {https://www.ncbi.nlm.nih.gov/pubmed/31413261}, author = {Deelen, Joris and Daniel S Evans and Dan E Arking and Tesi, Niccol{\`o} and Nygaard, Marianne and Liu, Xiaomin and Wojczynski, Mary K and Biggs, Mary L and van der Spek, Ashley and Atzmon, Gil and Erin B Ware and Sarnowski, Chlo{\'e} and Albert Vernon Smith and Sepp{\"a}l{\"a}, Ilkka and Cordell, Heather J and Dose, Janina and Amin, Najaf and Alice M. Arnold and Kristin L. Ayers and Barzilai, Nir and Becker, Elizabeth J and Beekman, Marian and Blanch{\'e}, H{\'e}l{\`e}ne and Christensen, Kaare and Christiansen, Lene and Collerton, Joanna C and Cubaynes, Sarah and Steven R Cummings and Davies, Karen and Debrabant, Birgit and Deleuze, Jean-Fran{\c c}ois and Duncan, Rachel and Jessica Faul and Franceschi, Claudio and Galan, Pilar and Gudnason, Vilmundur and Tamara B Harris and Huisman, Martijn and Hurme, Mikko A and Jagger, Carol and Jansen, Iris and Jylh{\"a}, Marja and K{\"a}h{\"o}nen, Mika and Karasik, David and Sharon L R Kardia and Kingston, Andrew and Kirkwood, Thomas B L and Lenore J Launer and Lehtim{\"a}ki, Terho and Lieb, Wolfgang and Lyytik{\"a}inen, Leo-Pekka and Martin-Ruiz, Carmen and Min, Junxia and Nebel, Almut and Anne B Newman and Nie, Chao and Nohr, Ellen A and Orwoll, Eric S and Thomas T Perls and Province, Michael A and Psaty, Bruce M and Olli T Raitakari and Reinders, Marcel J T and Robine, Jean-Marie and Rotter, Jerome I and Sebastiani, Paola and Jennifer A Smith and S{\o}rensen, Thorkild I A and Kent D Taylor and Andr{\'e} G Uitterlinden and van der Flier, Wiesje and Sven J van der Lee and Cornelia M van Duijn and van Heemst, Diana and James W Vaupel and David R Weir and Ye, Kenny and Zeng, Yi and Zheng, Wanlin and Holstege, Henne and Douglas P Kiel and Kathryn L Lunetta and Eline P Slagboom and Joanne M Murabito} } @article {10003, title = {Genetics of human longevity from incomplete data: New findings from the long life family study.}, journal = {Journals of Gerontology, Series A: Biological Sciences \& Medical Sciences}, volume = {73}, year = {2018}, month = {10/2018}, pages = {1472-1481}, abstract = {The special design of the Long Life Family Study provides a unique opportunity to investigate the genetics of human longevity by analyzing data on exceptional lifespans in families. In this article, we performed two series of genome wide association studies of human longevity which differed with respect to whether missing lifespan data were predicted or not predicted. We showed that the use of predicted lifespan is most beneficial when the follow-up period is relatively short. In addition to detection of strong associations of SNPs in APOE, TOMM40, NECTIN2, and APOC1 genes with longevity, we also detected a strong new association with longevity of rs1927465, located between the CYP26A1 and MYOF genes on chromosome 10. The association was confirmed using data from the Health and Retirement Study. We discuss the biological relevance of the detected SNPs to human longevity.}, keywords = {Genetics, Longevity}, issn = {1758-535X}, doi = {10.1093/gerona/gly057}, author = {Anatoliy Yashin and Konstantin G Arbeev and Wu, Deqing and Liubov S Arbeeva and Bagley, Olivia and Stallard, Eric and Alexander M Kulminski and Akushevich, Igor and Fang, Fang and Wojczynski, Mary K and Christensen, Kaare and Anne B Newman and Boudreau, Robert M and Province, Michael A and Stephen M Thielke and Thomas T Perls and An, Ping and Irma Elo and Svetlana Ukraintseva} } @article {7502, title = {Cross-national comparison of sex differences in health and mortality in Denmark, Japan and the US.}, journal = {Eur J Epidemiol}, volume = {25}, year = {2010}, month = {2010 Jul}, pages = {471-80}, publisher = {25}, abstract = {

The present study aims to compare the direction and magnitude of sex differences in mortality and major health dimensions across Denmark, Japan and the US. The Human Mortality Database was used to examine sex differences in age-specific mortality rates. The Danish twin surveys, the Danish 1905-Cohort Study, the Health and Retirement Study, and the Nihon University Japanese Longitudinal Study of Aging were used to examine sex differences in health. Men had consistently higher mortality rates at all ages in all three countries, but they also had a substantial advantage in handgrip strength compared with the same-aged women. Sex differences in activities of daily living (ADL) became pronounced among individuals aged 85+ in all three countries. Depression levels tended to be higher in women, particularly, in Denmark and the HRS, and only small sex differences were observed in the immediate recall test and Mini-Mental State Exam. The present study revealed consistent sex differentials in survival and physical health, self-rated health and cognition at older ages, whereas the pattern of sex differences in depressive symptoms was country-specific.

}, keywords = {Aged, Aged, 80 and over, Denmark, Disability Evaluation, Female, Health Status, Humans, Japan, Male, Middle Aged, Mortality, Sex Distribution, United States}, issn = {1573-7284}, doi = {10.1007/s10654-010-9460-6}, author = {Oksuzyan, Anna and Eileen M. Crimmins and Saito, Yasuhiko and Angela M O{\textquoteright}Rand and James W Vaupel and Christensen, Kaare} }