1. SPARK: A US Cohort of 50,000 Families to Accelerate Autism Research
Pamela Feliciano, Amy M. Daniels, LeeAnne Green Snyder, Amy Beaumont, Alexies Camba, Amy Esler, Amanda G. Gulsrud, Andrew Mason, Anibal Gutierrez, Amy Nicholson, Anna Marie Paolicelli, Alexander P. McKenzie, Angela L. Rachubinski, Alexandra N. Stephens, Andrea R. Simon, Amy Stedman, Amanda D. Shocklee, Amy Swanson, Brenda Finucane, Brittani A. Hilscher, Brenda Hauf, Brian J. O’Roak, Brooke McKenna, Beverly E. Robertson, Barbara Rodriguez, Brianna M. Vernoia, Bonnie Van Metre, Catherine Bradley, Cheryl Cohen, Craig A. Erickson, Christina Harkins, Caitlin Hayes, Catherine Lord, Christa Lese Martin, Crissy Ortiz, Cesar Ochoa-Lubinoff, Christine Peura, Catherine E. Rice, Cordelia R. Rosenberg, Christopher J. Smith, Carrie Thomas, Cora M. Taylor, Loran Casey White, Corrie H. Walston, David G. Amaral, Daniel Lee Coury, Dustin E. Sarver, Dalia Istephanous, Deana Li, Dzung Cong Nugyen, Emily A. Fox, Eric M. Butter, Elizabeth Berry-Kravis, Eric Courchesne, Eric J. Fombonne, Eugenia Hofammann, Elena Lamarche, Ericka L. Wodka, Emily T. Matthews, Eirene O’Connor, Emily Palen, Fiona Miller, Gabriel S. Dichter, Gabriela Marzano, Gail Stein, Hanna Hutter, Hannah E. Kaplan, Hai Li, Holly Lechniak, Hoa Lam Schneider, Hana Zaydens, Ivette Arriaga, Jennifer A. Gerdts, Joseph F. Cubells, Jeanette M. Cordova, Jaclyn Gunderson, Joseph Lillard, Julie Manoharan, James T. McCracken, Jacob J. Michaelson, Jason Neely, Jessica Orobio, Juhi Pandey, Joseph Piven, Jessica Scherr, James S. Sutcliffe, Jennifer Tjernagel, Jermel Wallace, Kristen Callahan, Katherine Dent, Kathryn A. Schweers, Kira E. Hamer, J. Kiely Law, Kathryn Lowe, Kaela O’Brien, Kaitlin Smith, Katherine G. Pawlowski, Karen L. Pierce, Katherine Roeder, Leonard J. Abbeduto, Leandra N. Berry, Lindsey A. Cartner, Leigh A. Coppola, Laura Carpenter, Lisa Cordeiro, Lindsey DeMarco, Luke P. Grosvenor, Lorrin Higgins, Lark Y. Huang-Storms, Landon Hosmer-Quint, Lynette M. Herbert, Lauren Kasparson, Lisa M. Prock, Lillian D. Pacheco, Laurie Raymond, Laura Simon, Latha V. Soorya, Lucy Wasserburg, Maya Lazar, Michael Alessandri, Melissa Brown, Mary Hannah Currin, McLeod F. Gwynette, Michelle Heyman, Melissa N. Hale, Mark Jones, Michelle Jordy, Michael J. Morrier, Mustafa Sahin, Matthew S. Siegel, Mary Verdi, Meaghan Venezia Parlade, Meredith Yinger, Nicole Bardett, Nathan Hanna, Nina Harris, Natalie Pottschmidt, Nicole Russo-Ponsaran, Nicole Takahashi, Opal Y. Ousley, A. Pablo Juarez, Patricia Manning, Robert D. Annett, Raphael A. Bernier, Renee D. Clark, Rebecca J. Landa, Robin P. Goin-Kochel, Rick Remington, Robert T. Schultz, Stephanie J. Brewster, Stephanie Booker, Sarah Carpenter, Sara Eldred, Sunday Francis, Sandra L. Friedman, Susannah Horner, Susan Hepburn, Suma Jacob, Stephen Kanne, Soo J. Lee, Sarah A. Mastel, Samantha Plate, Shanping Qiu, Sophia Sandhu, Samantha Thompson, Sabrina White, Vincent J. Myers, Vini Singh, Wha S. Yang, Zachary Warren, Alpha Amatya, Andrea J. Ace, Ahmad S. Chatha, Alex E. Lash, Ben Negron, Chris Rigby, Curtis Ridenour, Colleen M. Stock, Danielle Schmidt, Ian Fisk, John Acampado, Jay L. Nestle, Jay A. Nestle, Kevin Layman, Martin E. Butler, Matt Kent, Malcolm D. Mallardi, Nicholas Carriero, Noah Lawson, Natalia Volfovsky, Ron Edgar, Richard Marini, Rishiraj Rana, Swami Ganesan, Swapnil Shah, Tyler Ramsey, Wubin Chin, William Jensen, Anthony D. Krentz, Angela J. Gruber, Aniko Sabo, Andrei Salomatov, Christine Eng, Donna Muzny, Irina Astrovskaya, Richard A. Gibbs, Xinwei Han, Yufeng Shen, Louis F. Reichardt, Wendy K. Chung Pamela Feliciano, Amy M. Daniels, LeeAnne Green Snyder, Amy Beaumont, Alexies Camba, Amy Esler, Amanda G. Gulsrud, Andrew Mason, Anibal Gutierrez, Amy Nicholson, Anna Marie Paolicelli, Alexander P. McKenzie, Angela L. Rachubinski, Alexandra N. Stephens, Andrea R. Simon, Amy Stedman, Amanda D. Shocklee, Amy Swanson, Brenda Finucane, Brittani A. Hilscher, Brenda Hauf, Brian J. O’Roak, Brooke McKenna, Beverly E. Robertson, Barbara Rodriguez, Brianna M. Vernoia, Bonnie Van Metre, Catherine Bradley, Cheryl Cohen, Craig A. Erickson, Christina Harkins, Caitlin Hayes, Catherine Lord, Christa Lese Martin, Crissy Ortiz, Cesar Ochoa-Lubinoff, Christine Peura, Catherine E. Rice, Cordelia R. Rosenberg, Christopher J. Smith, Carrie Thomas, Cora M. Taylor, Loran Casey White, Corrie H. Walston, David G. Amaral, Daniel Lee Coury, Dustin E. Sarver, Dalia Istephanous, Deana Li, Dzung Cong Nugyen, Emily A. Fox, Eric M. Butter, Elizabeth Berry-Kravis, Eric Courchesne, Eric J. Fombonne, Eugenia Hofammann, Elena Lamarche, Ericka L. Wodka, Emily T. Matthews, Eirene O’Connor, Emily Palen, Fiona Miller, Gabriel S. Dichter, Gabriela Marzano, Gail Stein, Hanna Hutter, Hannah E. Kaplan, Hai Li, Holly Lechniak, Hoa Lam Schneider, Hana Zaydens, Ivette Arriaga, Jennifer A. Gerdts, Joseph F. Cubells, Jeanette M. Cordova, Jaclyn Gunderson, Joseph Lillard, Julie Manoharan, James T. McCracken, Jacob J. Michaelson, Jason Neely, Jessica Orobio, Juhi Pandey, Joseph Piven, Jessica Scherr, James S. Sutcliffe, Jennifer Tjernagel, Jermel Wallace, Kristen Callahan, Katherine Dent, Kathryn A. Schweers, Kira E. Hamer, J. Kiely Law, Kathryn Lowe, Kaela O’Brien, Kaitlin Smith, Katherine G. Pawlowski, Karen L. Pierce, Katherine Roeder, Leonard J. Abbeduto, Leandra N. Berry, Lindsey A. Cartner, Leigh A. Coppola, Laura Carpenter, Lisa Cordeiro, Lindsey DeMarco, Luke P. Grosvenor, Lorrin Higgins, Lark Y. Huang-Storms, Landon Hosmer-Quint, Lynette M. Herbert, Lauren Kasparson, Lisa M. Prock, Lillian D. Pacheco, Laurie Raymond, Laura Simon, Latha V. Soorya, Lucy Wasserburg, Maya Lazar, Michael Alessandri, Melissa Brown, Mary Hannah Currin, McLeod F. Gwynette, Michelle Heyman, Melissa N. Hale, Mark Jones, Michelle Jordy, Michael J. Morrier, Mustafa Sahin, Matthew S. Siegel, Mary Verdi, Meaghan Venezia Parlade, Meredith Yinger, Nicole Bardett, Nathan Hanna, Nina Harris, Natalie Pottschmidt, Nicole Russo-Ponsaran, Nicole Takahashi, Opal Y. Ousley, A. Pablo Juarez, Patricia Manning, Robert D. Annett, Raphael A. Bernier, Renee D. Clark, Rebecca J. Landa, Robin P. Goin-Kochel, Rick Remington, Robert T. Schultz, Stephanie J. Brewster, Stephanie Booker, Sarah Carpenter, Sara Eldred, Sunday Francis, Sandra L. Friedman, Susannah Horner, Susan Hepburn, Suma Jacob, Stephen Kanne, Soo J. Lee, Sarah A. Mastel, Samantha Plate, Shanping Qiu, Sophia Sandhu, Samantha Thompson, Sabrina White, Vincent J. Myers, Vini Singh, Wha S. Yang, Zachary Warren, Alpha Amatya, Andrea J. Ace, Ahmad S. Chatha, Alex E. Lash, Ben Negron, Chris Rigby, Curtis Ridenour, Colleen M. Stock, Danielle Schmidt, Ian Fisk, John Acampado, Jay L. Nestle, Jay A. Nestle, Kevin Layman, Martin E. Butler, Matt Kent, Malcolm D. Mallardi, Nicholas Carriero, Noah Lawson, Natalia Volfovsky, Ron Edgar, Richard Marini, Rishiraj Rana, Swami Ganesan, Swapnil Shah, Tyler Ramsey, Wubin Chin, William Jensen, Anthony D. Krentz, Angela J. Gruber, Aniko Sabo, Andrei Salomatov, Christine Eng, Donna Muzny, Irina Astrovskaya, Richard A. Gibbs, Xinwei Han, Yufeng Shen, Louis F. Reichardt, Wendy K. Chung 
Neuron 
Volume 97, Issue 3, Pages (February 2018)
DOI: /j.neuron
Copyright © 2018 Elsevier Inc. Terms and Conditions

2. Figure 1 Recruitment of the SPARK Cohort
(A) Statistical power to detect individual ASD risk genes based on excess of de novo variants. For a given sample size (number of trios), we calculate the expected number of de novo likely gene disrupting (LGD) (M1) or D-mis (damaging missense defined by meta-SVM) (Dong et al., 2015) (M2) for each gene by gene-specific background mutation rate calibrated in previous publications (Ware et al., 2015; Homsy et al., 2015). We assume that the observed number of such variants in a risk gene follows a Poisson distribution with mean of M1∗R + M2∗R/2, in which R is the relative risk of a de novo LGD variant in a risk gene. We then calculate the power of detecting the excess of de novo LGD and D-mis variants at a significance threshold of 2.6 × 10−6 to account for ∼19,000 protein-coding genes captured by WES and with the available background mutation rate data. The figure shows the average power of all genes given the sample size and R. With WES of 50,000 trios, we achieve greater than 70% power to detect an association based on de novo LGD and D-mis variants if R (relative risk) is 30 or above.
(B) In the first year of recruitment, 18,809 individuals with ASD (higher density indicated by larger circles) and 27,794 of their first-degree relatives consented to participate in SPARK, 81% of whom were recruited through the clinical sites (indicated by black dots). 15,302 of the individuals with ASD are children (<18 years) and 2,787 are adults. 7,610 unaffected full biological siblings were enrolled. The cohort includes 6,309 trios (proband, biological mother, and biological father), 682 sets of multi-gestational pregnancies with individuals with ASD (664 twin, 15 triplet, and three quadruplet sets that included 1,371 individuals with ASD), and 1,944 multiplex families in which at least one first-degree relative of the ASD proband also has ASD.
Neuron  , DOI: ( /j.neuron )
Copyright © 2018 Elsevier Inc. Terms and Conditions