A multicenter study to map genes for Fuchs endothelial corneal dystrophy: Baseline characteristics and heritability

Megan D. Louttit, Laura J. Kopplin, Robert P. Igo, Jeremy R. Fondran, Angela Tagliaferri, David Bardenstein, Anthony J. Aldave, Christopher R. Croasdale, Marianne O. Price, George O. Rosenwasser, Jonathan H. Lass, Sudha K. Iyengar, Francis W. Price, Kathleen Kelly, Stephen Hamilton, Barry Lee, Sanjay Patel, Keith Baratz, William Bourne, Leo MaguireJonathan Lass, William Reinhart, George Rosenwasser, David D. Verdier, Vinod Mootha, Wayne Bowman, H. Dwight Cavanagh, James P. McCulley, Steven Verity, Joel Sugar, Elmer Tu, Matthew S. Oliva, Walter M. Rotkis, Richard Yee, Mark Vital, James W. Caudill, Kristin Hammersmith, Brandon Ayres, Elizabeth Cohen, Peter Laibson, Christopher Rapuano, Kathryn Colby, Ula Jurkunas, Steven P. Dunn, David G. Heidemann, Alan Sugar, Shahzad Mian, H. Kaz Soong, Eduardo Alfonso, Carol Karp, Yunhee Lee, Sonia Yoo, Mark Gorovoy, Steven I. Rosenfeld, Marlene Brown, Elizabeth A. Davis, Ahmad Fahmy, David R. Hardten, Scott Hauswirth, Richard L. Lindstrom, Mark D. Mifflin, Randall Olson, Donald Stone, B. J. Dupps, David M. Meisler, Brandon Suedekum, Neda Shamie, Mark A. Terry, Samir Shah, Michael W. Belin, Todd Morason, Robert L. Schultze, Paul G. Galentine

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Methods: Twenty-nine enrolling sites with 62 trained investigators and coordinators gathered individual and family information, graded the phenotype, and collected blood and/or saliva for genetic analysis on all individuals with and without FECD. The degree of FECD was assessed in a 0 to 6 semiquantitative scale using standardized clinical methods with pathological verification of FECD on at least 1 member of each family. Central corneal thickness was measured by ultrasonic pachymetry.

Purpose: To describe the methods for family and case-control recruitment for a multicenter genetic and associated heritability analyses of Fuchs endothelial corneal dystrophy (FECD).

Results: Three hundred twenty-two families with 330 affected sibling pairs with FECD were enrolled and included a total of 650 sibling pairs of all disease grades. Using the entire 7-step FECD grading scale or a dichotomous definition of severe disease, heritability was assessed in families via sib-sib correlations. Both binary indicators of severe disease and semiquantitative measures of disease severity were significantly heritable, with heritability estimates of 30% for severe disease, 37% to 39% for FECD score, and 47% for central corneal thickness.

Conclusions: Genetic risk factors have a strong role in the severity of the FECD phenotype and corneal thickness. Genotyping this cohort with high-density genetic markers followed by appropriate statistical analyses should lead to novel loci for disease susceptibility.

Original languageEnglish (US)
Pages (from-to)26-35
Number of pages10
JournalCornea
Volume31
Issue number1
StatePublished - Jan 1 2012

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Fuchs' Endothelial Dystrophy
Multicenter Studies
Genes
Siblings
Phenotype
Disease Susceptibility
Genetic Markers
Saliva
Ultrasonics
Research Personnel

Keywords

  • Corneal thickness
  • Fuchs dystrophy
  • Genetics
  • Heritability

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Louttit, M. D., Kopplin, L. J., Igo, R. P., Fondran, J. R., Tagliaferri, A., Bardenstein, D., ... Galentine, P. G. (2012). A multicenter study to map genes for Fuchs endothelial corneal dystrophy: Baseline characteristics and heritability. Cornea, 31(1), 26-35.

A multicenter study to map genes for Fuchs endothelial corneal dystrophy : Baseline characteristics and heritability. / Louttit, Megan D.; Kopplin, Laura J.; Igo, Robert P.; Fondran, Jeremy R.; Tagliaferri, Angela; Bardenstein, David; Aldave, Anthony J.; Croasdale, Christopher R.; Price, Marianne O.; Rosenwasser, George O.; Lass, Jonathan H.; Iyengar, Sudha K.; Price, Francis W.; Kelly, Kathleen; Hamilton, Stephen; Lee, Barry; Patel, Sanjay; Baratz, Keith; Bourne, William; Maguire, Leo; Lass, Jonathan; Reinhart, William; Rosenwasser, George; Verdier, David D.; Mootha, Vinod; Bowman, Wayne; Cavanagh, H. Dwight; McCulley, James P.; Verity, Steven; Sugar, Joel; Tu, Elmer; Oliva, Matthew S.; Rotkis, Walter M.; Yee, Richard; Vital, Mark; Caudill, James W.; Hammersmith, Kristin; Ayres, Brandon; Cohen, Elizabeth; Laibson, Peter; Rapuano, Christopher; Colby, Kathryn; Jurkunas, Ula; Dunn, Steven P.; Heidemann, David G.; Sugar, Alan; Mian, Shahzad; Soong, H. Kaz; Alfonso, Eduardo; Karp, Carol; Lee, Yunhee; Yoo, Sonia; Gorovoy, Mark; Rosenfeld, Steven I.; Brown, Marlene; Davis, Elizabeth A.; Fahmy, Ahmad; Hardten, David R.; Hauswirth, Scott; Lindstrom, Richard L.; Mifflin, Mark D.; Olson, Randall; Stone, Donald; Dupps, B. J.; Meisler, David M.; Suedekum, Brandon; Shamie, Neda; Terry, Mark A.; Shah, Samir; Belin, Michael W.; Morason, Todd; Schultze, Robert L.; Galentine, Paul G.

In: Cornea, Vol. 31, No. 1, 01.01.2012, p. 26-35.

Research output: Contribution to journalArticle

Louttit, MD, Kopplin, LJ, Igo, RP, Fondran, JR, Tagliaferri, A, Bardenstein, D, Aldave, AJ, Croasdale, CR, Price, MO, Rosenwasser, GO, Lass, JH, Iyengar, SK, Price, FW, Kelly, K, Hamilton, S, Lee, B, Patel, S, Baratz, K, Bourne, W, Maguire, L, Lass, J, Reinhart, W, Rosenwasser, G, Verdier, DD, Mootha, V, Bowman, W, Cavanagh, HD, McCulley, JP, Verity, S, Sugar, J, Tu, E, Oliva, MS, Rotkis, WM, Yee, R, Vital, M, Caudill, JW, Hammersmith, K, Ayres, B, Cohen, E, Laibson, P, Rapuano, C, Colby, K, Jurkunas, U, Dunn, SP, Heidemann, DG, Sugar, A, Mian, S, Soong, HK, Alfonso, E, Karp, C, Lee, Y, Yoo, S, Gorovoy, M, Rosenfeld, SI, Brown, M, Davis, EA, Fahmy, A, Hardten, DR, Hauswirth, S, Lindstrom, RL, Mifflin, MD, Olson, R, Stone, D, Dupps, BJ, Meisler, DM, Suedekum, B, Shamie, N, Terry, MA, Shah, S, Belin, MW, Morason, T, Schultze, RL & Galentine, PG 2012, 'A multicenter study to map genes for Fuchs endothelial corneal dystrophy: Baseline characteristics and heritability', Cornea, vol. 31, no. 1, pp. 26-35.
Louttit MD, Kopplin LJ, Igo RP, Fondran JR, Tagliaferri A, Bardenstein D et al. A multicenter study to map genes for Fuchs endothelial corneal dystrophy: Baseline characteristics and heritability. Cornea. 2012 Jan 1;31(1):26-35.
Louttit, Megan D. ; Kopplin, Laura J. ; Igo, Robert P. ; Fondran, Jeremy R. ; Tagliaferri, Angela ; Bardenstein, David ; Aldave, Anthony J. ; Croasdale, Christopher R. ; Price, Marianne O. ; Rosenwasser, George O. ; Lass, Jonathan H. ; Iyengar, Sudha K. ; Price, Francis W. ; Kelly, Kathleen ; Hamilton, Stephen ; Lee, Barry ; Patel, Sanjay ; Baratz, Keith ; Bourne, William ; Maguire, Leo ; Lass, Jonathan ; Reinhart, William ; Rosenwasser, George ; Verdier, David D. ; Mootha, Vinod ; Bowman, Wayne ; Cavanagh, H. Dwight ; McCulley, James P. ; Verity, Steven ; Sugar, Joel ; Tu, Elmer ; Oliva, Matthew S. ; Rotkis, Walter M. ; Yee, Richard ; Vital, Mark ; Caudill, James W. ; Hammersmith, Kristin ; Ayres, Brandon ; Cohen, Elizabeth ; Laibson, Peter ; Rapuano, Christopher ; Colby, Kathryn ; Jurkunas, Ula ; Dunn, Steven P. ; Heidemann, David G. ; Sugar, Alan ; Mian, Shahzad ; Soong, H. Kaz ; Alfonso, Eduardo ; Karp, Carol ; Lee, Yunhee ; Yoo, Sonia ; Gorovoy, Mark ; Rosenfeld, Steven I. ; Brown, Marlene ; Davis, Elizabeth A. ; Fahmy, Ahmad ; Hardten, David R. ; Hauswirth, Scott ; Lindstrom, Richard L. ; Mifflin, Mark D. ; Olson, Randall ; Stone, Donald ; Dupps, B. J. ; Meisler, David M. ; Suedekum, Brandon ; Shamie, Neda ; Terry, Mark A. ; Shah, Samir ; Belin, Michael W. ; Morason, Todd ; Schultze, Robert L. ; Galentine, Paul G. / A multicenter study to map genes for Fuchs endothelial corneal dystrophy : Baseline characteristics and heritability. In: Cornea. 2012 ; Vol. 31, No. 1. pp. 26-35.
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T2 - Baseline characteristics and heritability

AU - Louttit, Megan D.

AU - Kopplin, Laura J.

AU - Igo, Robert P.

AU - Fondran, Jeremy R.

AU - Tagliaferri, Angela

AU - Bardenstein, David

AU - Aldave, Anthony J.

AU - Croasdale, Christopher R.

AU - Price, Marianne O.

AU - Rosenwasser, George O.

AU - Lass, Jonathan H.

AU - Iyengar, Sudha K.

AU - Price, Francis W.

AU - Kelly, Kathleen

AU - Hamilton, Stephen

AU - Lee, Barry

AU - Patel, Sanjay

AU - Baratz, Keith

AU - Bourne, William

AU - Maguire, Leo

AU - Lass, Jonathan

AU - Reinhart, William

AU - Rosenwasser, George

AU - Verdier, David D.

AU - Mootha, Vinod

AU - Bowman, Wayne

AU - Cavanagh, H. Dwight

AU - McCulley, James P.

AU - Verity, Steven

AU - Sugar, Joel

AU - Tu, Elmer

AU - Oliva, Matthew S.

AU - Rotkis, Walter M.

AU - Yee, Richard

AU - Vital, Mark

AU - Caudill, James W.

AU - Hammersmith, Kristin

AU - Ayres, Brandon

AU - Cohen, Elizabeth

AU - Laibson, Peter

AU - Rapuano, Christopher

AU - Colby, Kathryn

AU - Jurkunas, Ula

AU - Dunn, Steven P.

AU - Heidemann, David G.

AU - Sugar, Alan

AU - Mian, Shahzad

AU - Soong, H. Kaz

AU - Alfonso, Eduardo

AU - Karp, Carol

AU - Lee, Yunhee

AU - Yoo, Sonia

AU - Gorovoy, Mark

AU - Rosenfeld, Steven I.

AU - Brown, Marlene

AU - Davis, Elizabeth A.

AU - Fahmy, Ahmad

AU - Hardten, David R.

AU - Hauswirth, Scott

AU - Lindstrom, Richard L.

AU - Mifflin, Mark D.

AU - Olson, Randall

AU - Stone, Donald

AU - Dupps, B. J.

AU - Meisler, David M.

AU - Suedekum, Brandon

AU - Shamie, Neda

AU - Terry, Mark A.

AU - Shah, Samir

AU - Belin, Michael W.

AU - Morason, Todd

AU - Schultze, Robert L.

AU - Galentine, Paul G.

PY - 2012/1/1

Y1 - 2012/1/1

N2 - Methods: Twenty-nine enrolling sites with 62 trained investigators and coordinators gathered individual and family information, graded the phenotype, and collected blood and/or saliva for genetic analysis on all individuals with and without FECD. The degree of FECD was assessed in a 0 to 6 semiquantitative scale using standardized clinical methods with pathological verification of FECD on at least 1 member of each family. Central corneal thickness was measured by ultrasonic pachymetry.Purpose: To describe the methods for family and case-control recruitment for a multicenter genetic and associated heritability analyses of Fuchs endothelial corneal dystrophy (FECD).Results: Three hundred twenty-two families with 330 affected sibling pairs with FECD were enrolled and included a total of 650 sibling pairs of all disease grades. Using the entire 7-step FECD grading scale or a dichotomous definition of severe disease, heritability was assessed in families via sib-sib correlations. Both binary indicators of severe disease and semiquantitative measures of disease severity were significantly heritable, with heritability estimates of 30% for severe disease, 37% to 39% for FECD score, and 47% for central corneal thickness.Conclusions: Genetic risk factors have a strong role in the severity of the FECD phenotype and corneal thickness. Genotyping this cohort with high-density genetic markers followed by appropriate statistical analyses should lead to novel loci for disease susceptibility.

AB - Methods: Twenty-nine enrolling sites with 62 trained investigators and coordinators gathered individual and family information, graded the phenotype, and collected blood and/or saliva for genetic analysis on all individuals with and without FECD. The degree of FECD was assessed in a 0 to 6 semiquantitative scale using standardized clinical methods with pathological verification of FECD on at least 1 member of each family. Central corneal thickness was measured by ultrasonic pachymetry.Purpose: To describe the methods for family and case-control recruitment for a multicenter genetic and associated heritability analyses of Fuchs endothelial corneal dystrophy (FECD).Results: Three hundred twenty-two families with 330 affected sibling pairs with FECD were enrolled and included a total of 650 sibling pairs of all disease grades. Using the entire 7-step FECD grading scale or a dichotomous definition of severe disease, heritability was assessed in families via sib-sib correlations. Both binary indicators of severe disease and semiquantitative measures of disease severity were significantly heritable, with heritability estimates of 30% for severe disease, 37% to 39% for FECD score, and 47% for central corneal thickness.Conclusions: Genetic risk factors have a strong role in the severity of the FECD phenotype and corneal thickness. Genotyping this cohort with high-density genetic markers followed by appropriate statistical analyses should lead to novel loci for disease susceptibility.

KW - Corneal thickness

KW - Fuchs dystrophy

KW - Genetics

KW - Heritability

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