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Clonal hematopoiesis (CH)—age-related expansion of mutated hematopoietic clones—can differ in frequency and cellular fitness by CH type (e.g., mutations in driver genes (CHIP), gains/losses and copy-neutral loss of chromosomal segments (mCAs), and loss of sex chromosomes). Co-occurring CH raises questions as to their origin, selection, and impact. We integrate sequence and genotype array data in up to 482,378 UK Biobank participants to demonstrate shared genetic architecture across CH types. Our analysis suggests a cellular evolutionary trade-off between different types of CH, with LOY occurring at lower rates in individuals carrying mutations in established CHIP genes. We observed co-occurrence of CHIP and mCAs with overlap at TET2, DNMT3A, and JAK2, in which CHIP precedes mCA acquisition. Furthermore, individuals carrying overlapping CH had high risk of future lymphoid and myeloid malignancies. Finally, we leverage shared genetic architecture of CH traits to identify 15 novel loci associated with leukemia risk. Types of clonal hematopoiesis (CH) differ in frequency and fitness. These findings uncover shared genetic architecture, suggest evolutionary trade-offs between CH types, and detail elevated leukemia risk in individuals with overlapping types of CH. [ABSTRACT FROM AUTHOR]

Abstract: Urinary incontinence is defined by the International Continence Society (ICS) as ‘a condition where involuntary loss of urine is a social or hygienic problem and is objectively demonstrable’. It represents failure to store urine during the filling phase, either as a result of an abnormal detrusor (overactive, oversensitive) or an abnormal sphincter complex (i.e. too weak). It is a common and distressing problem and it has far-reaching effects on the life of an individual, with functional, psychological and social sequelae. It affects about 3.5 million people in the UK, though the figure may be as high as 10 million because many sufferers do not seek help despite, or because of, the social embarrassment caused. The elderly are particularly vulnerable, and women are affected more than men. The prevalence of treatment for incontinence in the UK is 8.5% for women and 1.6% for men in the 15–64 years age group, while the figures for those 65 years and over are 11.6% for women and 6.9% for men. Urine loss is either urethral or extra-urethral; extra-urethral loss is secondary to abnormal anatomy (e.g. ectopic ureter, rectovesical or vesico-vaginal fistulae). As LUT function is dependent on neural inputs from the central nervous system as well, neurological conditions (e.g. multiple sclerosis, Parkinson''s disease or spinal cord disease/injury) commonly cause incontinence. Urinary incontinence sometimes heralds the presence of such a disorder. [Copyright &y& Elsevier]