Edwards Digna R Velez, Gilbert John R, Jiang Lan, Gallins Paul J, Caywood Laura, Creason Marilyn, Fuzzell Denise, Knebusch Clare, Jackson Charles E, Pericak-Vance Margaret A, Haines Jonathan L, Scott William K
Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA.
Ann Hum Genet. 2011 Jul;75(4):516-28. doi: 10.1111/j.1469-1809.2011.00658.x.
Successful aging (SA) is a multidimensional phenotype involving preservation of cognitive ability, physical function, and social engagement throughout life. Multiple components of SA are heritable, supporting a genetic component. The Amish are genetically and socially isolated with homogeneous lifestyles, making them a suitable population for studying the genetics of SA. DNA and measures of SA were collected on 214 cognitively intact Amish individuals over age 80. Individuals were grouped into a 13-generation pedigree using the Anabaptist Genealogy Database. A linkage screen of 5944 single nucleotide polymorphisms (SNPs) was performed using 12 informative subpedigrees with an affected-only 2-point and multipoint linkage analysis. Eleven SNPs produced 2-point LOD scores >2, suggestive of linkage. Multipoint linkage analyses, allowing for heterogeneity, detected significant LOD scores on chromosomes 6 (HLOD = 4.50), 7 (LOD*= 3.11), and 14 (HLOD = 4.17), suggesting multiple new loci underlying SA.
成功老龄化(SA)是一种多维度的表型,涉及一生中认知能力、身体功能和社会参与度的维持。SA的多个组成部分具有遗传性,这支持了其遗传成分。阿米什人在基因和社会方面相对隔离,生活方式同质化,这使他们成为研究SA遗传学的合适人群。我们收集了214名80岁以上认知功能完好的阿米什人的DNA和SA测量数据。利用再洗礼派家谱数据库将个体分组为一个13代的家系。使用12个信息丰富的子家系进行了5944个单核苷酸多态性(SNP)的连锁筛选,并进行了仅受累个体的两点和多点连锁分析。11个SNP产生的两点LOD得分>2,提示存在连锁。考虑到异质性的多点连锁分析在6号染色体(HLOD = 4.50)、7号染色体(LOD* = 3.11)和14号染色体(HLOD = 4.17)上检测到显著的LOD得分,提示SA存在多个新的基因座。