Genomewide linkage analysis to presbycusis in the Framingham Heart Study
Genomewide linkage analysis to presbycusis in the Framingham Heart Study
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DOI：
10.1001/archotol.129.3.285
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发表时间：
2003-03-01
影响因子：
--
通讯作者：
Baldwin, CT
中科院分区：
文献类型：
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作者：
DeStefano, AL;Gates, GA;Baldwin, CT
目的：确定显示与年龄相关性听力损伤相关证据的染色体区域设计：我们评估了在不考虑听力状态的情况下确定的基于人群的样本中，听力测定检查的定量测量与全基因组扫描的标记之间的遗传联系。参与者：对国家心脏、肺和血液研究所的Frachial Heart研究的2263名原始队列成员和2217名后代队列成员进行了听力检查。其中，1789个个体是用于连锁分析的328个扩展家系的成员。连锁分析的结果性状为：（0.5、1.0和2.0 kHz）和低（0.25、0.5和1.0 kHz）频率，针对队列、性别、年龄、年龄平方和年龄立方进行调整。我们发现，遗传力（由于基因的方差比例）的年龄调整后的纯音平均在中频和低频分别为0.38和0.31。全基因组连锁分析确定了几个位置的连锁暗示的证据。特别感兴趣的是区域11 p（最大多点对数的优势[MLOD]，1.57），11 q13.5（MLOD，2.10），和14 q（MLOD，1.55），与已知的基因重叠，导致先天性deaths.Conclusions：有证据表明，遗传和环境因素有助于听力损失的成熟人群。几个染色体位置与已知导致先天性听力损失的基因座重叠。需要进一步的研究来确定是否相同的基因导致老年性耳聋和先天性听力损失。
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.