Jatinder Singh1, Ryan L Minster1, Nicole Schupf2, Aldi Kraja3, YongMei Liu4, Kaare Christensen5, Anne B Newman6, Candace M Kammerer1. 1. Department of Human Genetics, University of Pittsburgh, Pennsylvania. 2. Taub Institute for Research on Alzheimer's Disease and the Aging Brain, New York. 3. Division of Statistical Genomics, School of Medicine, Washington University in St. Louis, Missouri. 4. Department of Epidemiology & Prevention, Wake Forest University Health Sciences, Winston-Salem, North Carolina. 5. The Danish Aging Research Center, University of Southern Denmark; Department of Clinical Biochemistry and Pharmacology and Department of Clinical Genetics, Odense University Hospital, Denmark. 6. Department of Epidemiology, University of Pittsburgh, Pennsylvania.
Abstract
BACKGROUND: Identification of genes or fundamental biological pathways that regulate aging phenotypes and longevity could lead to possible interventions to increase healthy longevity. METHODS: Using data from the Long Life Family Study, we performed genomewide association analyses on an endophenotype construct, LF1, comprising a linear combination of traits across health domains. LF1 primarily reflected traits from the pulmonary and physical activity domains. RESULTS: We detected a significant association between LF1 and a locus on chromosome 10p15 (p-value = 4.65 × 10-8) and suggestive evidence (p-value < 5 × 10-6) for association on chromosomes 1, 2, 8, 12, 15, 18, and 22. Using data from the Health, Aging and Body Composition Study, we subsequently replicated the association for the 1p13 region near the NBPF6 locus (p-value = 3.65 × 10-4). CONCLUSIONS: Our analyses indicate that loci influencing a healthy aging endophenotype construct predominantly comprised of pulmonary and physical function domains may be located on chromosome 1p13 near the NBPF6 locus. Further investigation of this possible locus and other suggestive loci may reveal novel biological pathways that influence healthy aging.
BACKGROUND: Identification of genes or fundamental biological pathways that regulate aging phenotypes and longevity could lead to possible interventions to increase healthy longevity. METHODS: Using data from the Long Life Family Study, we performed genomewide association analyses on an endophenotype construct, LF1, comprising a linear combination of traits across health domains. LF1 primarily reflected traits from the pulmonary and physical activity domains. RESULTS: We detected a significant association between LF1 and a locus on chromosome 10p15 (p-value = 4.65 × 10-8) and suggestive evidence (p-value < 5 × 10-6) for association on chromosomes 1, 2, 8, 12, 15, 18, and 22. Using data from the Health, Aging and Body Composition Study, we subsequently replicated the association for the 1p13 region near the NBPF6 locus (p-value = 3.65 × 10-4). CONCLUSIONS: Our analyses indicate that loci influencing a healthy aging endophenotype construct predominantly comprised of pulmonary and physical function domains may be located on chromosome 1p13 near the NBPF6 locus. Further investigation of this possible locus and other suggestive loci may reveal novel biological pathways that influence healthy aging.
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