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 |
State | Published - Jan 1 2012 |
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Keywords
- Corneal thickness
- Fuchs dystrophy
- Genetics
- Heritability
ASJC Scopus subject areas
- Ophthalmology
Cite this
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 journal › Article
}
TY - JOUR
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
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
UR - http://www.scopus.com/inward/record.url?scp=84856494249&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856494249&partnerID=8YFLogxK
M3 - Article
C2 - 22045388
AN - SCOPUS:84856494249
VL - 31
SP - 26
EP - 35
JO - Cornea
JF - Cornea
SN - 0277-3740
IS - 1
ER -