@article {714, title = {Short-term variability of respiration and sleep during unattended nonlaboratory polysomnography--the Sleep Heart Health Study. [corrected].}, journal = {Sleep}, volume = {25}, year = {2002}, month = {2002 Dec}, pages = {843-9}, abstract = {

STUDY OBJECTIVES: To determine the short-term variability of indices of disturbed respiration and sleep during 2 nights of unattended nonlaboratory polysomnography conducted several months apart.

DESIGN: Participants were randomly selected using a block design with stratification on preliminary estimates of 2 criteria: respiratory disturbance index [RDI3\% (apnea or hypopnea events associated with > or = 3\% O2 desaturation): < 15/hour total sleep time, > or = 15/hour total sleep time] and sleep efficiency (SEff: < 85\% and > or = 85\%). The RDI and sleep data from initial and repeated polysomnography were compared.

SETTING: NA.

PARTICIPANTS: A subset of 99 participants in the Sleep Heart Health Study who agreed to have a repeat polysomnogram within 4 months of their original study.

INTERVENTIONS: NA.

MEASUREMENTS AND RESULTS: Acceptable repeat polysomnograms were obtained in 91 subjects (mean study interval: 77 +/- 18 [sd] days; range: 31-112 days). There was no significant bias in RDI between study nights using several different RDI definitions including RDI3\% and RDI4\% (apnea or hypopnea events associated with > or = 4\% O2 desaturation). Variability between studies estimated using intraclass correlations (ICC) ranged from 0.77 to 0.81. For subjects with a RDI3\% < 15, variability increased as a function of increasing RDI, but for those with a RDI3\% > or = 15, variability was constant. Body mass index, SEff, gender, or age did not directly predict RDI variability. Using RDI4\% cutpoints of < or = 5, < or = 10 and < or = 15 events per hour of sleep demonstrated that 79.1\%, 85.7\%, and 87.9\% of subjects, respectively, had the same classification of SDB status on both nights of study. There also was no significant bias in sleep staging, sleep efficiency, or arousal index between studies. However, variability was greater with ICC values ranging from 0.37 (\% time in REM) to 0.76 (arousal index).

CONCLUSION: In the Sleep Heart Health Study, accurate estimates of the severity of sleep-disordered breathing and the quality of sleep were obtained from a single night of unattended nonlaboratory polysomnography. These findings may be applicable to other large epidemiologic studies provided that similar recording techniques and quality-assurance procedures are followed.

}, keywords = {Adult, Aged, Aged, 80 and over, Apnea, Arousal, Body Mass Index, Circadian Rhythm, Electrocardiography, Electromyography, Electrooculography, Female, Humans, Male, Middle Aged, Oxygen Consumption, Polysomnography, Respiration, Sleep Apnea Syndromes, Sleep Stages, Time Factors}, issn = {0161-8105}, author = {Quan, Stuart F and Griswold, Michael E and Iber, Conrad and Nieto, F Javier and Rapoport, David M and Redline, Susan and Sanders, Mark and Young, Terry} } @article {6590, title = {Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks.}, journal = {Am J Hum Genet}, volume = {94}, year = {2014}, month = {2014 Feb 06}, pages = {223-32}, abstract = {

Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the "Exome Array" to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1\% and 2\%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121*], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited.

}, keywords = {1-Alkyl-2-acetylglycerophosphocholine Esterase, Adult, African Continental Ancestry Group, Aged, Alleles, Animals, Cholesterol, HDL, Cholesterol, LDL, Cohort Studies, Coronary Disease, European Continental Ancestry Group, Female, Gene Frequency, Genetic Association Studies, Genetic Code, Genetic Variation, Humans, Linear Models, Male, Mice, Mice, Inbred C57BL, Microtubule-Associated Proteins, Middle Aged, Phenotype, Sequence Analysis, DNA, Subtilisins, Triglycerides}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2014.01.009}, author = {Peloso, Gina M and Auer, Paul L and Bis, Joshua C and Voorman, Arend and Morrison, Alanna C and Stitziel, Nathan O and Brody, Jennifer A and Khetarpal, Sumeet A and Crosby, Jacy R and Fornage, Myriam and Isaacs, Aaron and Jakobsdottir, Johanna and Feitosa, Mary F and Davies, Gail and Huffman, Jennifer E and Manichaikul, Ani and Davis, Brian and Lohman, Kurt and Joon, Aron Y and Smith, Albert V and Grove, Megan L and Zanoni, Paolo and Redon, Valeska and Demissie, Serkalem and Lawson, Kim and Peters, Ulrike and Carlson, Christopher and Jackson, Rebecca D and Ryckman, Kelli K and Mackey, Rachel H and Robinson, Jennifer G and Siscovick, David S and Schreiner, Pamela J and Mychaleckyj, Josyf C and Pankow, James S and Hofman, Albert and Uitterlinden, Andr{\'e} G and Harris, Tamara B and Taylor, Kent D and Stafford, Jeanette M and Reynolds, Lindsay M and Marioni, Riccardo E and Dehghan, Abbas and Franco, Oscar H and Patel, Aniruddh P and Lu, Yingchang and Hindy, George and Gottesman, Omri and Bottinger, Erwin P and Melander, Olle and Orho-Melander, Marju and Loos, Ruth J F and Duga, Stefano and Merlini, Piera Angelica and Farrall, Martin and Goel, Anuj and Asselta, Rosanna and Girelli, Domenico and Martinelli, Nicola and Shah, Svati H and Kraus, William E and Li, Mingyao and Rader, Daniel J and Reilly, Muredach P and McPherson, Ruth and Watkins, Hugh and Ardissino, Diego and Zhang, Qunyuan and Wang, Judy and Tsai, Michael Y and Taylor, Herman A and Correa, Adolfo and Griswold, Michael E and Lange, Leslie A and Starr, John M and Rudan, Igor and Eiriksdottir, Gudny and Launer, Lenore J and Ordovas, Jose M and Levy, Daniel and Chen, Y-D Ida and Reiner, Alexander P and Hayward, Caroline and Polasek, Ozren and Deary, Ian J and Borecki, Ingrid B and Liu, Yongmei and Gudnason, Vilmundur and Wilson, James G and van Duijn, Cornelia M and Kooperberg, Charles and Rich, Stephen S and Psaty, Bruce M and Rotter, Jerome I and O{\textquoteright}Donnell, Christopher J and Rice, Kenneth and Boerwinkle, Eric and Kathiresan, Sekar and Cupples, L Adrienne} } @article {6577, title = {Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol.}, journal = {Am J Hum Genet}, volume = {94}, year = {2014}, month = {2014 Feb 06}, pages = {233-45}, abstract = {

Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or <2(nd) percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments.

}, keywords = {Adult, Aged, Apolipoproteins E, Cholesterol, LDL, Cohort Studies, Dyslipidemias, Exome, Female, Follow-Up Studies, Gene Frequency, Genetic Code, Genome-Wide Association Study, Genotype, Humans, Lipase, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Proprotein Convertase 9, Proprotein Convertases, Receptors, LDL, Sequence Analysis, DNA, Serine Endopeptidases}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2014.01.010}, author = {Lange, Leslie A and Hu, Youna and Zhang, He and Xue, Chenyi and Schmidt, Ellen M and Tang, Zheng-Zheng and Bizon, Chris and Lange, Ethan M and Smith, Joshua D and Turner, Emily H and Jun, Goo and Kang, Hyun Min and Peloso, Gina and Auer, Paul and Li, Kuo-Ping and Flannick, Jason and Zhang, Ji and Fuchsberger, Christian and Gaulton, Kyle and Lindgren, Cecilia and Locke, Adam and Manning, Alisa and Sim, Xueling and Rivas, Manuel A and Holmen, Oddgeir L and Gottesman, Omri and Lu, Yingchang and Ruderfer, Douglas and Stahl, Eli A and Duan, Qing and Li, Yun and Durda, Peter and Jiao, Shuo and Isaacs, Aaron and Hofman, Albert and Bis, Joshua C and Correa, Adolfo and Griswold, Michael E and Jakobsdottir, Johanna and Smith, Albert V and Schreiner, Pamela J and Feitosa, Mary F and Zhang, Qunyuan and Huffman, Jennifer E and Crosby, Jacy and Wassel, Christina L and Do, Ron and Franceschini, Nora and Martin, Lisa W and Robinson, Jennifer G and Assimes, Themistocles L and Crosslin, David R and Rosenthal, Elisabeth A and Tsai, Michael and Rieder, Mark J and Farlow, Deborah N and Folsom, Aaron R and Lumley, Thomas and Fox, Ervin R and Carlson, Christopher S and Peters, Ulrike and Jackson, Rebecca D and van Duijn, Cornelia M and Uitterlinden, Andr{\'e} G and Levy, Daniel and Rotter, Jerome I and Taylor, Herman A and Gudnason, Vilmundur and Siscovick, David S and Fornage, Myriam and Borecki, Ingrid B and Hayward, Caroline and Rudan, Igor and Chen, Y Eugene and Bottinger, Erwin P and Loos, Ruth J F and S{\ae}trom, P{\r a}l and Hveem, Kristian and Boehnke, Michael and Groop, Leif and McCarthy, Mark and Meitinger, Thomas and Ballantyne, Christie M and Gabriel, Stacey B and O{\textquoteright}Donnell, Christopher J and Post, Wendy S and North, Kari E and Reiner, Alexander P and Boerwinkle, Eric and Psaty, Bruce M and Altshuler, David and Kathiresan, Sekar and Lin, Dan-Yu and Jarvik, Gail P and Cupples, L Adrienne and Kooperberg, Charles and Wilson, James G and Nickerson, Deborah A and Abecasis, Goncalo R and Rich, Stephen S and Tracy, Russell P and Willer, Cristen J} } @article {6684, title = {Genome-wide studies of verbal declarative memory in nondemented older people: the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium.}, journal = {Biol Psychiatry}, volume = {77}, year = {2015}, month = {2015 Apr 15}, pages = {749-63}, abstract = {

BACKGROUND: Memory performance in older persons can reflect genetic influences on cognitive function and dementing processes. We aimed to identify genetic contributions to verbal declarative memory in a community setting.

METHODS: We conducted genome-wide association studies for paragraph or word list delayed recall in 19 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, comprising 29,076 dementia- and stroke-free individuals of European descent, aged >=45 years. Replication of suggestive associations (p < 5 {\texttimes} 10(-6)) was sought in 10,617 participants of European descent, 3811 African-Americans, and 1561 young adults.

RESULTS: rs4420638, near APOE, was associated with poorer delayed recall performance in discovery (p = 5.57 {\texttimes} 10(-10)) and replication cohorts (p = 5.65 {\texttimes} 10(-8)). This association was stronger for paragraph than word list delayed recall and in the oldest persons. Two associations with specific tests, in subsets of the total sample, reached genome-wide significance in combined analyses of discovery and replication (rs11074779 [HS3ST4], p = 3.11 {\texttimes} 10(-8), and rs6813517 [SPOCK3], p = 2.58 {\texttimes} 10(-8)) near genes involved in immune response. A genetic score combining 58 independent suggestive memory risk variants was associated with increasing Alzheimer disease pathology in 725 autopsy samples. Association of memory risk loci with gene expression in 138 human hippocampus samples showed cis-associations with WDR48 and CLDN5, both related to ubiquitin metabolism.

CONCLUSIONS: This largest study to date exploring the genetics of memory function in ~40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways.

}, keywords = {Aged, Aged, 80 and over, Aging, Apolipoproteins E, Claudin-5, Cohort Studies, Female, Genome-Wide Association Study, Genotype, Humans, Male, Memory Disorders, Middle Aged, Polymorphism, Single Nucleotide, Proteins, Proteoglycans, Regression Analysis, Sulfotransferases, Verbal Learning}, issn = {1873-2402}, doi = {10.1016/j.biopsych.2014.08.027}, author = {Debette, Stephanie and Ibrahim Verbaas, Carla A and Bressler, Jan and Schuur, Maaike and Smith, Albert and Bis, Joshua C and Davies, Gail and Wolf, Christiane and Gudnason, Vilmundur and Chibnik, Lori B and Yang, Qiong and DeStefano, Anita L and de Quervain, Dominique J F and Srikanth, Velandai and Lahti, Jari and Grabe, Hans J and Smith, Jennifer A and Priebe, Lutz and Yu, Lei and Karbalai, Nazanin and Hayward, Caroline and Wilson, James F and Campbell, Harry and Petrovic, Katja and Fornage, Myriam and Chauhan, Ganesh and Yeo, Robin and Boxall, Ruth and Becker, James and Stegle, Oliver and Mather, Karen A and Chouraki, Vincent and Sun, Qi and Rose, Lynda M and Resnick, Susan and Oldmeadow, Christopher and Kirin, Mirna and Wright, Alan F and Jonsdottir, Maria K and Au, Rhoda and Becker, Albert and Amin, Najaf and Nalls, Mike A and Turner, Stephen T and Kardia, Sharon L R and Oostra, Ben and Windham, Gwen and Coker, Laura H and Zhao, Wei and Knopman, David S and Heiss, Gerardo and Griswold, Michael E and Gottesman, Rebecca F and Vitart, Veronique and Hastie, Nicholas D and Zgaga, Lina and Rudan, Igor and Polasek, Ozren and Holliday, Elizabeth G and Schofield, Peter and Choi, Seung Hoan and Tanaka, Toshiko and An, Yang and Perry, Rodney T and Kennedy, Richard E and Sale, Mich{\`e}le M and Wang, Jing and Wadley, Virginia G and Liewald, David C and Ridker, Paul M and Gow, Alan J and Pattie, Alison and Starr, John M and Porteous, David and Liu, Xuan and Thomson, Russell and Armstrong, Nicola J and Eiriksdottir, Gudny and Assareh, Arezoo A and Kochan, Nicole A and Widen, Elisabeth and Palotie, Aarno and Hsieh, Yi-Chen and Eriksson, Johan G and Vogler, Christian and van Swieten, John C and Shulman, Joshua M and Beiser, Alexa and Rotter, Jerome and Schmidt, Carsten O and Hoffmann, Wolfgang and N{\"o}then, Markus M and Ferrucci, Luigi and Attia, John and Uitterlinden, Andr{\'e} G and Amouyel, Philippe and Dartigues, Jean-Fran{\c c}ois and Amieva, H{\'e}l{\`e}ne and R{\"a}ikk{\"o}nen, Katri and Garcia, Melissa and Wolf, Philip A and Hofman, Albert and Longstreth, W T and Psaty, Bruce M and Boerwinkle, Eric and DeJager, Philip L and Sachdev, Perminder S and Schmidt, Reinhold and Breteler, Monique M B and Teumer, Alexander and Lopez, Oscar L and Cichon, Sven and Chasman, Daniel I and Grodstein, Francine and M{\"u}ller-Myhsok, Bertram and Tzourio, Christophe and Papassotiropoulos, Andreas and Bennett, David A and Ikram, M Arfan and Deary, Ian J and van Duijn, Cornelia M and Launer, Lenore and Fitzpatrick, Annette L and Seshadri, Sudha and Mosley, Thomas H} } @article {7788, title = {Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.}, journal = {Nat Commun}, volume = {9}, year = {2018}, month = {2018 May 29}, pages = {2098}, abstract = {

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 {\texttimes} 10) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3\% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

}, issn = {2041-1723}, doi = {10.1038/s41467-018-04362-x}, author = {Davies, Gail and Lam, Max and Harris, Sarah E and Trampush, Joey W and Luciano, Michelle and Hill, W David and Hagenaars, Saskia P and Ritchie, Stuart J and Marioni, Riccardo E and Fawns-Ritchie, Chloe and Liewald, David C M and Okely, Judith A and Ahola-Olli, Ari V and Barnes, Catriona L K and Bertram, Lars and Bis, Joshua C and Burdick, Katherine E and Christoforou, Andrea and DeRosse, Pamela and Djurovic, Srdjan and Espeseth, Thomas and Giakoumaki, Stella and Giddaluru, Sudheer and Gustavson, Daniel E and Hayward, Caroline and Hofer, Edith and Ikram, M Arfan and Karlsson, Robert and Knowles, Emma and Lahti, Jari and Leber, Markus and Li, Shuo and Mather, Karen A and Melle, Ingrid and Morris, Derek and Oldmeadow, Christopher and Palviainen, Teemu and Payton, Antony and Pazoki, Raha and Petrovic, Katja and Reynolds, Chandra A and Sargurupremraj, Muralidharan and Scholz, Markus and Smith, Jennifer A and Smith, Albert V and Terzikhan, Natalie and Thalamuthu, Anbupalam and Trompet, Stella and van der Lee, Sven J and Ware, Erin B and Windham, B Gwen and Wright, Margaret J and Yang, Jingyun and Yu, Jin and Ames, David and Amin, Najaf and Amouyel, Philippe and Andreassen, Ole A and Armstrong, Nicola J and Assareh, Amelia A and Attia, John R and Attix, Deborah and Avramopoulos, Dimitrios and Bennett, David A and B{\"o}hmer, Anne C and Boyle, Patricia A and Brodaty, Henry and Campbell, Harry and Cannon, Tyrone D and Cirulli, Elizabeth T and Congdon, Eliza and Conley, Emily Drabant and Corley, Janie and Cox, Simon R and Dale, Anders M and Dehghan, Abbas and Dick, Danielle and Dickinson, Dwight and Eriksson, Johan G and Evangelou, Evangelos and Faul, Jessica D and Ford, Ian and Freimer, Nelson A and Gao, He and Giegling, Ina and Gillespie, Nathan A and Gordon, Scott D and Gottesman, Rebecca F and Griswold, Michael E and Gudnason, Vilmundur and Harris, Tamara B and Hartmann, Annette M and Hatzimanolis, Alex and Heiss, Gerardo and Holliday, Elizabeth G and Joshi, Peter K and K{\"a}h{\"o}nen, Mika and Kardia, Sharon L R and Karlsson, Ida and Kleineidam, Luca and Knopman, David S and Kochan, Nicole A and Konte, Bettina and Kwok, John B and Le Hellard, Stephanie and Lee, Teresa and Lehtim{\"a}ki, Terho and Li, Shu-Chen and Liu, Tian and Koini, Marisa and London, Edythe and Longstreth, Will T and Lopez, Oscar L and Loukola, Anu and Luck, Tobias and Lundervold, Astri J and Lundquist, Anders and Lyytik{\"a}inen, Leo-Pekka and Martin, Nicholas G and Montgomery, Grant W and Murray, Alison D and Need, Anna C and Noordam, Raymond and Nyberg, Lars and Ollier, William and Papenberg, Goran and Pattie, Alison and Polasek, Ozren and Poldrack, Russell A and Psaty, Bruce M and Reppermund, Simone and Riedel-Heller, Steffi G and Rose, Richard J and Rotter, Jerome I and Roussos, Panos and Rovio, Suvi P and Saba, Yasaman and Sabb, Fred W and Sachdev, Perminder S and Satizabal, Claudia L and Schmid, Matthias and Scott, Rodney J and Scult, Matthew A and Simino, Jeannette and Slagboom, P Eline and Smyrnis, Nikolaos and Soumar{\'e}, A{\"\i}cha and Stefanis, Nikos C and Stott, David J and Straub, Richard E and Sundet, Kjetil and Taylor, Adele M and Taylor, Kent D and Tzoulaki, Ioanna and Tzourio, Christophe and Uitterlinden, Andre and Vitart, Veronique and Voineskos, Aristotle N and Kaprio, Jaakko and Wagner, Michael and Wagner, Holger and Weinhold, Leonie and Wen, K Hoyan and Widen, Elisabeth and Yang, Qiong and Zhao, Wei and Adams, Hieab H H and Arking, Dan E and Bilder, Robert M and Bitsios, Panos and Boerwinkle, Eric and Chiba-Falek, Ornit and Corvin, Aiden and De Jager, Philip L and Debette, Stephanie and Donohoe, Gary and Elliott, Paul and Fitzpatrick, Annette L and Gill, Michael and Glahn, David C and H{\"a}gg, Sara and Hansell, Narelle K and Hariri, Ahmad R and Ikram, M Kamran and Jukema, J Wouter and Vuoksimaa, Eero and Keller, Matthew C and Kremen, William S and Launer, Lenore and Lindenberger, Ulman and Palotie, Aarno and Pedersen, Nancy L and Pendleton, Neil and Porteous, David J and R{\"a}ikk{\"o}nen, Katri and Raitakari, Olli T and Ramirez, Alfredo and Reinvang, Ivar and Rudan, Igor and Schmidt, Reinhold and Schmidt, Helena and Schofield, Peter W and Schofield, Peter R and Starr, John M and Steen, Vidar M and Trollor, Julian N and Turner, Steven T and van Duijn, Cornelia M and Villringer, Arno and Weinberger, Daniel R and Weir, David R and Wilson, James F and Malhotra, Anil and McIntosh, Andrew M and Gale, Catharine R and Seshadri, Sudha and Mosley, Thomas H and Bressler, Jan and Lencz, Todd and Deary, Ian J} } @article {8489, title = {Carotid Intima-Media Thickness and the Risk of Sudden Cardiac Death: The ARIC Study and the CHS.}, journal = {J Am Heart Assoc}, volume = {9}, year = {2020}, month = {2020 Oct 20}, pages = {e016981}, abstract = {

Background Sudden cardiac death (SCD) is associated with severe coronary heart disease in the great majority of cases. Whether carotid intima-media thickness (C-IMT), a known surrogate marker of subclinical atherosclerosis, is associated with risk of SCD in a general population remains unknown. The objective of this study was to investigate the association between C-IMT and risk of SCD. Methods and Results We examined a total of 20~862 participants: 15~307 participants of the ARIC (Atherosclerosis Risk in Communities) study and 5555 participants of the CHS (Cardiovascular Health Study). C-IMT and common carotid artery intima-media thickness was measured at baseline by ultrasound. Presence of plaque was judged by trained readers. Over a median of 23.5~years of follow-up, 569 participants had SCD (1.81 cases per 1000 person-years) in the ARIC study. Mean C-IMT and common carotid artery intima-media thickness were associated with risk of SCD after adjustment for traditional risk factors and time-varying adjustors: hazard ratios (HRs) with 95\% CIs for fourth versus first quartile were 1.64 (1.15-2.63) and 1.49 (1.05-2.11), respectively. In CHS, 302 participants developed SCD (4.64 cases per 1000 person-years) over 13.1~years. Maximum C-IMT was associated with risk of SCD after adjustment: HR (95\% CI) for fourth versus first quartile was 1.75 (1.22-2.51). Presence of plaque was associated with 35\% increased risk of SCD: HR (95\% CI) of 1.37 (1.13-1.67) in the ARIC study and 1.32 (1.04-1.68) in CHS. Conclusions C-IMT was associated with risk of SCD in 2 biracial community-based cohorts. C-IMT may be used as a marker of SCD risk and potentially to initiate early therapeutic interventions to mitigate the risk.

}, issn = {2047-9980}, doi = {10.1161/JAHA.120.016981}, author = {Suzuki, Takeki and Wang, Wanmei and Wilsdon, Anthony and Butler, Kenneth R and Adabag, Selcuk and Griswold, Michael E and Nambi, Vijay and Rosamond, Wayne and Sotoodehnia, Nona and Mosley, Thomas H} } @article {9578, title = {Multi-omics and pathway analyses of genome-wide associations implicate regulation and immunity in verbal declarative memory performance.}, journal = {Alzheimers Res Ther}, volume = {16}, year = {2024}, month = {2024 Jan 20}, pages = {14}, abstract = {

BACKGROUND: Uncovering the functional relevance underlying verbal declarative memory (VDM) genome-wide association study (GWAS) results may facilitate the development of interventions to reduce age-related memory decline and dementia.

METHODS: We performed multi-omics and pathway enrichment analyses of paragraph (PAR-dr) and word list (WL-dr) delayed recall GWAS from 29,076 older non-demented individuals of European descent. We assessed the relationship between single-variant associations and expression quantitative trait loci (eQTLs) in 44 tissues and methylation quantitative trait loci (meQTLs) in the hippocampus. We determined the relationship between gene associations and transcript levels in 53 tissues, annotation as immune genes, and regulation by transcription factors (TFs) and microRNAs. To identify significant pathways, gene set enrichment was tested in each cohort and meta-analyzed across cohorts. Analyses of differential expression in brain tissues were conducted for pathway component genes.

RESULTS: The single-variant associations of VDM showed significant linkage disequilibrium (LD) with eQTLs across all tissues and meQTLs within the hippocampus. Stronger WL-dr gene associations correlated with reduced expression in four brain tissues, including the hippocampus. More robust PAR-dr and/or WL-dr gene associations were intricately linked with immunity and were influenced by 31 TFs and 2 microRNAs. Six pathways, including type I diabetes, exhibited significant associations with both PAR-dr and WL-dr. These pathways included fifteen MHC genes intricately linked to VDM performance, showing diverse expression patterns based on cognitive status in brain tissues.

CONCLUSIONS: VDM genetic associations influence expression regulation via eQTLs and meQTLs. The involvement of TFs, microRNAs, MHC genes, and immune-related pathways contributes to VDM performance in older individuals.

}, keywords = {Aged, Cognition, Genome-Wide Association Study, Humans, Memory, MicroRNAs, Multiomics, Polymorphism, Single Nucleotide}, issn = {1758-9193}, doi = {10.1186/s13195-023-01376-6}, author = {Mei, Hao and Simino, Jeannette and Li, Lianna and Jiang, Fan and Bis, Joshua C and Davies, Gail and Hill, W David and Xia, Charley and Gudnason, Vilmundur and Yang, Qiong and Lahti, Jari and Smith, Jennifer A and Kirin, Mirna and De Jager, Philip and Armstrong, Nicola J and Ghanbari, Mohsen and Kolcic, Ivana and Moran, Christopher and Teumer, Alexander and Sargurupremraj, Murali and Mahmud, Shamsed and Fornage, Myriam and Zhao, Wei and Satizabal, Claudia L and Polasek, Ozren and R{\"a}ikk{\"o}nen, Katri and Liewald, David C and Homuth, Georg and Callisaya, Michele and Mather, Karen A and Windham, B Gwen and Zemunik, Tatijana and Palotie, Aarno and Pattie, Alison and van der Auwera, Sandra and Thalamuthu, Anbupalam and Knopman, David S and Rudan, Igor and Starr, John M and Wittfeld, Katharina and Kochan, Nicole A and Griswold, Michael E and Vitart, Veronique and Brodaty, Henry and Gottesman, Rebecca and Cox, Simon R and Psaty, Bruce M and Boerwinkle, Eric and Chasman, Daniel I and Grodstein, Francine and Sachdev, Perminder S and Srikanth, Velandai and Hayward, Caroline and Wilson, James F and Eriksson, Johan G and Kardia, Sharon L R and Grabe, Hans J and Bennett, David A and Ikram, M Arfan and Deary, Ian J and van Duijn, Cornelia M and Launer, Lenore and Fitzpatrick, Annette L and Seshadri, Sudha and Bressler, Jan and Debette, Stephanie and Mosley, Thomas H} }