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 H. Baratz; William Bourne; Leo Maguire; 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

doi:10.1097/ICO.0b013e31821c9b8f

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 H. Baratz, William Bourne, Leo MaguireWilliam 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

Ophthalmology

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

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 language	English (US)
Pages (from-to)	26-35
Number of pages	10
Journal	Cornea
Volume	31
Issue number	1
DOIs	https://doi.org/10.1097/ICO.0b013e31821c9b8f
State	Published - Jan 1 2012

Keywords

Corneal thickness
Fuchs dystrophy
Genetics
Heritability

ASJC Scopus subject areas

Ophthalmology

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Louttit, M. D., Kopplin, L. J., Igo, R. P., Fondran, J. R., Tagliaferri, A., Bardenstein, D., Aldave, A. J., Croasdale, C. R., Price, M. O., Rosenwasser, G. O., Lass, J. H., Iyengar, S. K., Price, F. W., Kelly, K., Hamilton, S., Lee, B., Patel, S., Baratz, K. H., Bourne, W., ... Galentine, P. G. (2012). A multicenter study to map genes for Fuchs endothelial corneal dystrophy: Baseline characteristics and heritability. Cornea, 31(1), 26-35. https://doi.org/10.1097/ICO.0b013e31821c9b8f

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 H.; Bourne, William; Maguire, Leo; 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 journal › Article › peer-review

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, KH, Bourne, W, Maguire, L, 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. https://doi.org/10.1097/ICO.0b013e31821c9b8f

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 H. ; Bourne, William ; Maguire, Leo ; 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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title = "A multicenter study to map genes for Fuchs endothelial corneal dystrophy: Baseline characteristics and heritability",

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.",

keywords = "Corneal thickness, Fuchs dystrophy, Genetics, Heritability",

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

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T1 - A multicenter study to map genes for Fuchs endothelial corneal dystrophy

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 H.

AU - Bourne, William

AU - Maguire, Leo

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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