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Whole genome sequence analyses of brain imaging measures in the Framingham Study
- Sarnowski, Chloé;
- Satizabal, Claudia L;
- DeCarli, Charles;
- Pitsillides, Achilleas N;
- Cupples, L Adrienne;
- Vasan, Ramachandran S;
- Wilson, James G;
- Bis, Joshua C;
- Fornage, Myriam;
- Beiser, Alexa S;
- DeStefano, Anita L;
- Dupuis, Josée;
- Seshadri, Sudha;
- Arnett, Donna K;
- Becker, Diane;
- Bis, Joshua;
- Boerwinkle, Eric;
- Bowers, Michael;
- Bressler, Jan;
- Correa, Adolfo;
- DeStefano, Anita;
- Ding, Jingzhong ding;
- Fardo, David;
- Fornage, Myriam;
- Lugo, Alex Garcia;
- Glahn, David;
- Gonzalez, Hector;
- Hayden, Kathleen;
- Heckbert, Susan;
- Hoth, Karin;
- Hughes, Timothy;
- Jaquish, Cashell;
- Jian, Xueqiu;
- Knowles, Emma;
- Launer, Lenore;
- Lin, Honghuang;
- Longstreth, Will;
- Mayeux, Richard;
- Misra, Biswapriya;
- Mosley, Thomas;
- Nyquist, Paul;
- Olivier, Michael;
- Peprah, Emmanuel;
- Psaty, Bruce;
- Purcell, Shaun;
- Rotter, Jerome;
- Sarnowski, Chloé;
- Satizabal, Claudia;
- Schellenberg, Gerard;
- Seshadri, Sudha;
- Simino, Jeannette;
- Smith, Jennifer;
- Smoller, Sylvia;
- Snively, Beverly;
- Sokolow, Sophie;
- Wehr, Kate;
- Yanek, Lisa;
- Yang, Qiong;
- Namiko, Abe;
- Goncalo, Abecasis;
- Christine, Albert;
- Nicholette (Nichole) Palmer, Allred;
- Laura, Almasy;
- Alvaro, Alonso;
- Seth, Ament;
- Peter, Anderson;
- Pramod, Anugu;
- Deborah, Applebaum-Bowden;
- Dan, Arking;
- Donna K, Arnett;
- Allison, Ashley-Koch;
- Stella, Aslibekyan;
- Tim, Assimes;
- Paul, Auer;
- Dimitrios, Avramopoulos;
- John, Barnard;
- Kathleen, Barnes;
- Graham, Barr R;
- Emily, Barron-Casella;
- Terri, Beaty;
- Diane, Becker;
- Lewis, Becker;
- Rebecca, Beer;
- Ferdouse, Begum;
- Amber, Beitelshees;
- Emelia, Benjamin;
- Marcos, Bezerra;
- Larry, Bielak;
- Joshua, Bis;
- Thomas, Blackwell;
- John, Blangero;
- Eric, Boerwinkle;
- Ingrid, Borecki;
- Russell, Bowler;
- Jennifer, Brody;
- Ulrich, Broeckel;
- Jai, Broome;
- Karen, Bunting;
- Esteban, Burchard;
- Jonathan, Cardwell;
- Sara, Carlson;
- Cara, Carty;
- Richard, Casaburi;
- James, Casella;
- Mark, Chaffin;
- Christy, Chang;
- Daniel, Chasman;
- Sameer, Chavan;
- Bo-Juen, Chen;
- Wei-Min, Chen;
- Yii-Der Ida, Chen;
- Michael, Cho;
- Hoan, Choi Seung;
- Lee-Ming, Chuang;
- Mina, Chung;
- Elaine, Cornell;
- Adolfo, Correa;
- Carolyn, Crandall;
- James, Crapo;
- Adrienne, Cupples L;
- Joanne, Curran;
- Jeffrey, Curtis;
- Brian, Custer;
- Coleen, Damcott;
- Dawood, Darbar;
- Sayantan, Das;
- Sean, David;
- Colleen, Davis;
- de Andrade Mariza, Daya Michelle;
- Michael, DeBaun;
- Ranjan, Deka;
- Dawn, DeMeo;
- Scott, Devine;
- Ron, Do;
- Qing, Duan;
- Ravi, Duggirala;
- Peter, Durda;
- Susan, Dutcher;
- Charles, Eaton;
- Lynette, Ekunwe;
- Patrick, Ellinor;
- Leslie, Emery;
- Charles, Farber;
- Leanna, Farnam;
- Tasha, Fingerlin;
- Matthew, Flickinger;
- Myriam, Fornage;
- Nora, Franceschini;
- Mao, Fu;
- Malia, Fullerton;
- Lucinda, Fulton;
- Stacey, Gabriel;
- Weiniu, Gan;
- Yan, Gao;
- Margery, Gass;
- Xiaoqi (Priscilla), Geng;
- Soren, Germer;
- Chris, Gignoux;
- Mark, Gladwin;
- David, Glahn;
- Stephanie, Gogarten;
- Da-Wei, Gong;
- Harald, Goring;
- Charles, Gu C;
- Yue, Guan;
- Xiuqing, Guo;
- Jeff, Haessler;
- Michael, Hall;
- Daniel, Harris;
- Nicola, Hawley;
- Jiang, He;
- Ben, Heavner;
- Susan, Heckbert;
- Ryan, Hernandez;
- David, Herrington;
- Craig, Hersh;
- Bertha, Hidalgo;
- James, Hixson;
- John, Hokanson;
- Elliott, Hong;
- Karin, Hoth;
- Chao (Agnes), Hsiung;
- Haley, Huston;
- Min, Hwu Chii;
- Ryan, Irvin Marguerite;
- Rebecca, Jackson;
- Deepti, Jain;
- Cashell, Jaquish;
- Min A, Jhun;
- Jill, Johnsen;
- Andrew, Johnson;
- Craig, Johnson;
- Rich, Johnston;
- Kimberly, Jones;
- Min, Kang Hyun;
- Robert, Kaplan;
- Sharon, Kardia;
- Sekar, Kathiresan;
- Laura, Kaufman;
- Shannon, Kelly;
- Eimear, Kenny;
- Michael, Kessler;
- Alyna, Khan;
- Greg, Kinney;
- Barbara, Konkle;
- Charles, Kooperberg;
- Holly, Kramer;
- Stephanie, Krauter;
- Christoph, Lange;
- Ethan, Lange;
- Leslie, Lange;
- Cathy, Laurie;
- Cecelia, Laurie;
- Meryl, LeBoff;
- Shawn, Lee Seunggeun;
- Wen-Jane, Lee;
- Jonathon, LeFaive;
- David, Levine;
- Dan, Levy;
- Joshua, Lewis;
- Yun, Li;
- Honghuang, Lin;
- Han, Lin Keng;
- Simin, Liu;
- Yongmei, Liu;
- Ruth, Loos;
- Steven, Lubitz;
- Kathryn, Lunetta;
- James, Luo;
- Michael, Mahaney;
- Barry, Make;
- Ani, Manichaikul;
- JoAnn, Manson;
- Lauren, Margolin;
- Lisa, Martin;
- Susan, Mathai;
- Rasika, Mathias;
- Patrick, McArdle;
- Merry-Lynn, McDonald;
- Sean, McFarland;
- Stephen, McGarvey;
- Hao, Mei;
- Deborah A, Meyers;
- Julie, Mikulla;
- Nancy, Min;
- Mollie, Minear;
- Ryan L, Minster;
- Braxton, Mitchell;
- May E, Montasser;
- Solomon, Musani;
- Stanford, Mwasongwe;
- Josyf C, Mychaleckyj;
- Girish, Nadkarni;
- Rakhi, Naik;
- Pradeep, Natarajan;
- Sergei, Nekhai;
- Deborah, Nickerson;
- Kari, North;
- Jeff, O'Connell;
- Tim, O'Connor;
- Heather, Ochs-Balcom;
- James, Pankow;
- George, Papanicolaou;
- Margaret, Parker;
- Afshin, Parsa;
- Tangarone, Pattison Jessica;
- Sara, Penchev;
- Manuel, Peralta Juan;
- Marco, Perez;
- James, Perry;
- Ulrike, Peters;
- Patricia, Peyser;
- Larry, Phillips;
- Sam, Phillips;
- Toni, Pollin;
- Wendy, Post;
- Julia, Powers Becker;
- Meher, Preethi Boorgula;
- Michael, Preuss;
- Dmitry, Prokopenko;
- Bruce, Psaty;
- Pankaj, Qasba;
- Dandi, Qiao;
- Zhaohui, Qin;
- Nicholas, Rafaels;
- Laura, Raffield;
- Vasan, Ramachandran;
- Rao, DC;
- Laura, Rasmussen-Torvik;
- Aakrosh, Ratan;
- Susan, Redline;
- Robert, Reed;
- Elizabeth, Regan;
- Alex, Reiner;
- Ken, Rice;
- Stephen, Rich;
- Dan, Roden;
- Carolina, Roselli;
- Jerome, Rotter;
- Ingo, Ruczinski;
- Pamela, Russell;
- Sarah, Ruuska;
- Kathleen, Ryan;
- Phuwanat, Sakornsakolpat;
- Shabnam, Salimi;
- Steven, Salzberg;
- Kevin, Sandow;
- Vijay, Sankaran;
- Christopher, Scheller;
- Ellen, Schmidt;
- Karen, Schwander;
- David, Schwartz;
- Frank, Sciurba;
- Vivien, Sheehan;
- Amol, Shetty;
- Aniket, Shetty;
- Hui-Heng, Sheu Wayne;
- Benjamin, Shoemaker M;
- Brian, Silver;
- Edwin, Silverman;
- Jennifer, Smith;
- Josh, Smith;
- Nicholas, Smith;
- Tanja, Smith;
- Sylvia, Smoller;
- Beverly, Snively;
- Tamar, Sofer;
- Nona, Sotoodehnia;
- Adrienne, Stilp;
- Elizabeth, Streeten;
- Ju, Sung Yun;
- Jody, Sylvia;
- Adam, Szpiro;
- Carole, Sztalryd;
- Daniel, Taliun;
- Hua, Tang;
- Margaret, Taub;
- Kent, Taylor;
- Simeon, Taylor;
- Marilyn, Telen;
- Timothy A, Thornton;
- Lesley, Tinker;
- David, Tirschwell;
- Hemant, Tiwari;
- Russell, Tracy;
- Michael, Tsai;
- Dhananjay, Vaidya;
- Peter, VandeHaar;
- Scott, Vrieze;
- Tarik, Walker;
- Robert, Wallace;
- Avram, Walts;
- Emily, Wan;
- Fei, Wang Fei;
- Karol, Watson;
- Daniel E, Weeks;
- Bruce, Weir;
- Scott, Weiss;
- Lu-Chen, Weng;
- Cristen, Willer;
- Kayleen, Williams;
- Keoki, Williams L;
- Carla, Wilson;
- James, Wilson;
- Quenna, Wong;
- Huichun, Xu;
- Lisa, Yanek;
- Ivana, Yang;
- Rongze, Yang;
- Norann, Zaghloul;
- Yingze, Zhang;
- Xueyan, Zhao Snow;
- Wei, Zhao;
- Xiuwen, Zheng;
- Degui, Zhi;
- Xiang, Zhou;
- Michael, Zody;
- Sebastian, Zoellner
- et al.
Abstract
Objective
We sought to identify rare variants influencing brain imaging phenotypes in the Framingham Heart Study by performing whole genome sequence association analyses within the Trans-Omics for Precision Medicine Program.Methods
We performed association analyses of cerebral and hippocampal volumes and white matter hyperintensity (WMH) in up to 2,180 individuals by testing the association of rank-normalized residuals from mixed-effect linear regression models adjusted for sex, age, and total intracranial volume with individual variants while accounting for familial relatedness. We conducted gene-based tests for rare variants using (1) a sliding-window approach, (2) a selection of functional exonic variants, or (3) all variants.Results
We detected new loci in 1p21 for cerebral volume (minor allele frequency [MAF] 0.005, p = 10-8) and in 16q23 for hippocampal volume (MAF 0.05, p = 2.7 × 10-8). Previously identified associations in 12q24 for hippocampal volume (rs7294919, p = 4.4 × 10-4) and in 17q25 for WMH (rs7214628, p = 2.0 × 10-3) were confirmed. Gene-based tests detected associations (p ≤ 2.3 × 10-6) in new loci for cerebral (5q13, 8p12, 9q31, 13q12-q13, 15q24, 17q12, 19q13) and hippocampal volumes (2p12) and WMH (3q13, 4p15) including Alzheimer disease- (UNC5D) and Parkinson disease-associated genes (GBA). Pathway analyses evidenced enrichment of associated genes in immunity, inflammation, and Alzheimer disease and Parkinson disease pathways.Conclusions
Whole genome sequence-wide search reveals intriguing new loci associated with brain measures. Replication of novel loci is needed to confirm these findings.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.