Browsing by Subject "Heritability"

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    Biogenetic mechanisms predisposing to complex phenotypes in parents may function differently in their children.
    (J Gerontol A Biol Sci Med Sci, 2013-07) Kulminski, Alexander M; Arbeev, Konstantin G; Christensen, Kaare; Stallard, Eric; Miljkovic, Iva; Barmada, Michael; Yashin, Anatoliy I
    This study focuses on the participants of the Long Life Family Study to elucidate whether biogenetic mechanisms underlying relationships among heritable complex phenotypes in parents function in the same way for the same phenotypes in their children. Our results reveal 3 characteristic groups of relationships among phenotypes in parents and children. One group composed of 3 pairs of phenotypes confirms that associations among some phenotypes can be explained by the same biogenetic mechanisms working in parents and children. Two other groups including 9 phenotype pairs show that this is not a common rule. Our findings suggest that biogenetic mechanisms underlying relationships among different phenotypes, even if they are causally related, can function differently in successive generations or in different age groups of biologically related individuals. The results suggest that the role of aging-related processes in changing environment may be conceptually underestimated in current genetic association studies using genome wide resources.
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    Shared Inherited Genetics of Benign Prostatic Hyperplasia and Prostate Cancer.
    (European urology open science, 2022-09) Glaser, Alexander; Shi, Zhuqing; Wei, Jun; Lanman, Nadia A; Ladson-Gary, Skylar; Vickman, Renee E; Franco, Omar E; Crawford, Susan E; Lilly Zheng, S; Hayward, Simon W; Isaacs, William B; Helfand, Brian T; Xu, Jianfeng

    Background

    The association between benign prostatic hyperplasia (BPH) and prostate cancer (PCa) remains controversial, largely due to a detection bias in traditional observational studies.

    Objective

    To assess the association between BPH and PCa using inherited single nucleotide polymorphisms (SNPs).

    Design setting and participants

    The participants were White men from the population-based UK Biobank (UKB).

    Outcome measurements and statistical analysis

    The association between BPH and PCa was tested for (1) phenotypic correlation using chi-square, (2) genetic correlation (r g) based on genome-wide SNPs using linkage disequilibrium score regression, and (3) cross-disease genetic associations based on known risk-associated SNPs (15 for BPH and 239 for PCa), individually and cumulatively using genetic risk score (GRS).

    Results and limitations

    Among 214 717 White men in the UKB, 24 623 (11%) and 14 311 (6.7%) had a diagnosis of BPH and PCa, respectively. Diagnoses of these two diseases were significantly correlated (χ2 = 1862.80, p < 0.001). A significant genetic correlation was found (r g = 0.16; 95% confidence interval 0.03-0.28, p = 0.01). In addition, significant cross-disease genetic associations for established risk-associated SNPs were also found. Among the 250 established genome-wide association study-significant SNPs of PCa or BPH, 49 were significantly associated with the risk of the other disease at p < 0.05, significantly more than expected by chance (N = 12, p < 0.001; χ2 test). Furthermore, significant cross-disease GRS associations were also found; GRSBPH was significantly associated with PCa risk (odds ratio [OR] = 1.26 [1.18-1.36], p < 0.001), and GRSPCa was significantly associated with BPH risk (OR = 1.03 [1.02-1.04], p < 0.001). Moreover, GRSBPH was significantly and inversely associated with lethal PCa risk in a PCa case-case analysis (OR = 0.58 [0.41-0.81], p = 0.002). Only White men were studied.

    Conclusions

    BPH and PCa share common inherited genetics, which suggests that the phenotypic association of these two diseases in observational studies is not entirely caused by the detection bias.

    Patient summary

    For the first time, we found that benign prostatic hyperplasia and prostate cancer are genetically related. This finding may have implications in disease etiology and risk stratification.