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Full-Text Articles in Medical Sciences
Inherited Causes Of Clonal Haematopoiesis In 97,691 Whole Genomes, Alexander G. Bick, Joshua S. Weinstock, Satish K. Nandakumar, Charles P. Fulco, Erik L. Bao, Seyedeh M. Zekavat, Mindy D. Szeto, Juan M. Peralta, Joanne E. Curran, John Blangero
Inherited Causes Of Clonal Haematopoiesis In 97,691 Whole Genomes, Alexander G. Bick, Joshua S. Weinstock, Satish K. Nandakumar, Charles P. Fulco, Erik L. Bao, Seyedeh M. Zekavat, Mindy D. Szeto, Juan M. Peralta, Joanne E. Curran, John Blangero
School of Medicine Publications and Presentations
Age is the dominant risk factor for most chronic human diseases, but the mechanisms through which ageing confers this risk are largely unknown1. The age-related acquisition of somatic mutations that lead to clonal expansion in regenerating haematopoietic stem cell populations has recently been associated with both haematological cancer2,3,4 and coronary heart disease5—this phenomenon is termed clonal haematopoiesis of indeterminate potential (CHIP)6. Simultaneous analyses of germline and somatic whole-genome sequences provide the opportunity to identify root causes of CHIP. Here we analyse high-coverage whole-genome sequences from 97,691 participants of diverse …
A Large Genome-Wide Association Study Of Age-Related Macular Degeneration Highlights Contributions Of Rare And Common Variants, Lars G. Fritsche, Wilmar Igl, Jessica N. Cooke Bailey, Felix Grassmann, Sebanti Sengupta, Jennifer L. Bragg-Gresham, Kathryn P. Burdon, Scott J. Hebbring, Matthew P. Johnson, John Blangero
A Large Genome-Wide Association Study Of Age-Related Macular Degeneration Highlights Contributions Of Rare And Common Variants, Lars G. Fritsche, Wilmar Igl, Jessica N. Cooke Bailey, Felix Grassmann, Sebanti Sengupta, Jennifer L. Bragg-Gresham, Kathryn P. Burdon, Scott J. Hebbring, Matthew P. Johnson, John Blangero
School of Medicine Publications and Presentations
Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly with limited therapeutic options. Here, we report on a study of >12 million variants including 163,714 directly genotyped, most rare, protein-altering variant. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5×10–8) distributed across 34 loci. While wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first signal specific to wet AMD, near MMP9 (difference-P = 4.1×10–10). Very rare coding variants (frequency < 0.1%) in CFH, CFI, and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate …