biostudies-literatureChoi YNIA NIH HHSNIMH NIH HHSNHGRI NIH HHS785-98https://www.ebi.ac.uk/biostudies/studies/S-EPMC3168696biostudies-literatureUnknown156B(7)Alzheimer's disease (AD) is a common neurodegenerative disorder of late life with a complex genetic basis. Although several genes are known to play a role in rare early onset AD, only the APOE gene is known to have a high contribution to risk of the common late-onset form of the disease (LOAD, onset >60 years). APOE genotypes vary in their AD risk as well as age-at-onset distributions, and it is likely that other loci will similarly affect AD age-at-onset. Here we present the first analysis of age-at-onset in the NIMH LOAD sample that allows for both a multilocus trait model and genetic heterogeneity among the contributing sites, while at the same time accommodating age censoring, effects of known genetic covariates, and full pedigree and marker information. The results provide evidence for genomic regions not previously implicated in this data set, including regions on chromosomes 7q, 15, and 19p. They also affirm evidence for loci on chromosomes 1q, 6p, 9q, 11, and, of course, the APOE locus on 19q, all of which have been reported previously in the same sample. The analyses failed to find evidence for linkage to chromosome 10 with inclusion of unaffected subjects and extended pedigrees. Several regions implicated in these analyses in the NIMH sample have been previously reported in genome scans of other AD samples. These results, therefore, provide independent confirmation of AD loci in family-based samples on chromosomes 1q, 7q, 19p, and suggest that further efforts towards identifying the underlying causal loci are warranted.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric GeneticsGenome scan of age-at-onset in the NIMH Alzheimer disease sample uncovers multiple loci, along with evidence of both genetic and sample heterogeneity.PMC3168696U01 MH046290-08P50 AG005136U01 MH046281T32 AG000258-13U01 MH046290T32 AG000258-12U01 MH046373T32 AG000258P50 AG005136-27P50 AG005136-28P50 AG005136-25P50 AG005136-26U01 MH046373-04U01 MH046281-08N01 HG065403Marchani EEWijsman EMSteinbart EJBlacker DChoi YBird TDfalseGenome scan of age-at-onset in the NIMH Alzheimer disease sample uncovers multiple loci, along with evidence of both genetic and sample heterogeneity.Alzheimer's disease (AD) is a common neurodegenerative disorder of late life with a complex genetic basis. Although several genes are known to play a role in rare early onset AD, only the APOE gene is known to have a high contribution to risk of the common late-onset form of the disease (LOAD, onset >60 years). APOE genotypes vary in their AD risk as well as age-at-onset distributions, and it is likely that other loci will similarly affect AD age-at-onset. Here we present the first analysis of age-at-onset in the NIMH LOAD sample that allows for both a multilocus trait model and genetic heterogeneity among the contributing sites, while at the same time accommodating age censoring, effects of known genetic covariates, and full pedigree and marker information. The results provide evidence for genomic regions not previously implicated in this data set, including regions on chromosomes 7q, 15, and 19p. They also affirm evidence for loci on chromosomes 1q, 6p, 9q, 11, and, of course, the APOE locus on 19q, all of which have been reported previously in the same sample. The analyses failed to find evidence for linkage to chromosome 10 with inclusion of unaffected subjects and extended pedigrees. Several regions implicated in these analyses in the NIMH sample have been previously reported in genome scans of other AD samples. These results, therefore, provide independent confirmation of AD loci in family-based samples on chromosomes 1q, 7q, 19p, and suggest that further efforts towards identifying the underlying causal loci are warranted.2011-01-01T00:00:00Z2011 Dec2020-11-19T15:38:37Z2019-03-27T00:43:43ZS-EPMC31686962181209910.1002/ajmg.b.31220