OBJECTIVE: To identify chromosomal regions that show evidence of linkage to age-associated hearing impairment (presbycusis) in humans. DESIGN: We evaluated the genetic linkage between quantitative measures from audiometric examinations and markers from a genomewide scan in a population-based sample ascertained without respect to hearing status. PARTICIPANTS: Audiometric examinations were conducted on 2263 original cohort members and 2217 offspring cohort members of the National Heart, Lung, and Blood Institute's Framingham Heart Study. Of these, 1789 individuals were members of 328 extended pedigrees used for linkage analysis. The outcome traits for linkage analysis were pure-tone average at medium (0.5, 1.0, and 2.0 kHz) and low (0.25, 0.5, and 1.0 kHz) frequencies adjusted for cohort, sex, age, age squared, and age cubed. RESULTS: We found heritability (proportion of variance due to genes) of age-adjusted pure-tone average at medium and low frequencies to be 0.38 and 0.31, respectively. Genomewide linkage analysis identified several locations with suggestive evidence of linkage. Of particular interest are the regions 11p (maximum multipoint logarithm of odds [MLOD], 1.57), 11q13.5 (MLOD, 2.10), and 14q (MLOD, 1.55), which overlap with genes known to cause congenital deafness. CONCLUSIONS: There is evidence that genetic and environmental factors contribute to hearing loss in the mature human population. Several of the chromosomal locations identified overlap with loci known to cause congenital hearing loss. Further studies are needed to determine whether the same genes cause presbycusis and congenital hearing loss.
OBJECTIVE: To identify chromosomal regions that show evidence of linkage to age-associated hearing impairment (presbycusis) in humans. DESIGN: We evaluated the genetic linkage between quantitative measures from audiometric examinations and markers from a genomewide scan in a population-based sample ascertained without respect to hearing status. PARTICIPANTS: Audiometric examinations were conducted on 2263 original cohort members and 2217 offspring cohort members of the National Heart, Lung, and Blood Institute's Framingham Heart Study. Of these, 1789 individuals were members of 328 extended pedigrees used for linkage analysis. The outcome traits for linkage analysis were pure-tone average at medium (0.5, 1.0, and 2.0 kHz) and low (0.25, 0.5, and 1.0 kHz) frequencies adjusted for cohort, sex, age, age squared, and age cubed. RESULTS: We found heritability (proportion of variance due to genes) of age-adjusted pure-tone average at medium and low frequencies to be 0.38 and 0.31, respectively. Genomewide linkage analysis identified several locations with suggestive evidence of linkage. Of particular interest are the regions 11p (maximum multipoint logarithm of odds [MLOD], 1.57), 11q13.5 (MLOD, 2.10), and 14q (MLOD, 1.55), which overlap with genes known to cause congenital deafness. CONCLUSIONS: There is evidence that genetic and environmental factors contribute to hearing loss in the mature human population. Several of the chromosomal locations identified overlap with loci known to cause congenital hearing loss. Further studies are needed to determine whether the same genes cause presbycusis and congenital hearing loss.
Authors: Kevin W Christie; Elena Sivan-Loukianova; Wesley C Smith; Benjamin T Aldrich; Michael A Schon; Madhuparna Roy; Bridget C Lear; Daniel F Eberl Journal: Proc Natl Acad Sci U S A Date: 2013-09-03 Impact factor: 11.205
Authors: Kelly L Kane; Chantal M Longo-Guess; Leona H Gagnon; Dalian Ding; Richard J Salvi; Kenneth R Johnson Journal: Hear Res Date: 2011-11-22 Impact factor: 3.208
Authors: Jeroen R Huyghe; Lut Van Laer; Jan-Jaap Hendrickx; Erik Fransen; Kelly Demeester; Vedat Topsakal; Sylvia Kunst; Minna Manninen; Mona Jensen; Amanda Bonaconsa; Manuela Mazzoli; Manuela Baur; Samuli Hannula; Elina Mäki-Torkko; Angeles Espeso; Els Van Eyken; Antonia Flaquer; Christian Becker; Dafydd Stephens; Martti Sorri; Eva Orzan; Michael Bille; Agnete Parving; Ilmari Pyykkö; Cor W R J Cremers; Hannie Kremer; Paul H Van de Heyning; Thomas F Wienker; Peter Nürnberg; Markus Pfister; Guy Van Camp Journal: Am J Hum Genet Date: 2008-08-28 Impact factor: 11.025
Authors: M Zhu; T Yang; S Wei; A T DeWan; R J Morell; J L Elfenbein; R A Fisher; S M Leal; R J H Smith; K H Friderici Journal: Am J Hum Genet Date: 2003-09-16 Impact factor: 11.025