Genome-wide association study of prostate-specific antigen levels identifies novel loci independent of prostate cancer

Hoffmann, Thomas J.; Passarelli, Michael N.; Graff, Rebecca E.; Emami, Nima C.; Sakoda, Lori C.; Jorgenson, Eric; Habel, Laurel A.; Shan, Jun; Ranatunga, Dilrini K.; Quesenberry, Charles P.; Chao, Chun; Ghai, Nirupa R.; Aaronson, David S.; Presti, Joseph C.; Nordström, Tobias; Wang, Zhaoming; Berndt, Sonja I.; Chanock, Stephen J.; Mosley, Jonathan D.; Klein, Robert J.; Middha, Mridu; Lilja, Hans; Melander, Olle; Kvale, Mark N.; Kwok, Pui Yan; Schaefer, Catherine; Risch, Neil; Eeden, Stephen K. Van Den; Witte, John S.

doi:10.1038/ncomms14248

Cited by 58 publications

(64 citation statements)

References 83 publications

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“…One possible solution for this issue is reanalysis of existing GWAS data. Indeed, a focused survey of the literature reveals that when re-analyses included the X chromosome, novel and biologically relevant genetic findings were detected for diabetes mellitus type 2 [145], prostate cancer [146], and orofacial clefts [147]. To the best of our knowledge, such reanalyses have not yet been conducted for ASD and ADHD.…”

Section: Adhd In Scasmentioning

confidence: 99%

Sex differences in psychiatric disorders: what we can learn from sex chromosome aneuploidies

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Reiss

2018

Neuropsychopharmacol

130

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The study of sexual dimorphism in psychiatric and neurodevelopmental disorders is challenging due to the complex interplay of diverse biological, psychological, and social factors. Males are more susceptible to neurodevelopmental disorders including intellectual disability, autism spectrum disorder, and attention-deficit activity disorder. Conversely, after puberty, females are more prone to major depressive disorder and anxiety disorders compared to males. One major biological factor contributing to sex differences is the sex chromosomes. First, the X and Y chromosomes have unique and specific genetic effects as well as downstream gonadal effects. Second, males have one X chromosome and one Y chromosome, while females have two X chromosomes. Thus, sex chromosome constitution also differs between the sexes. Due to this complexity, determining genetic and downstream biological influences on sexual dimorphism in humans is challenging. Sex chromosome aneuploidies, such as Turner syndrome (X0) and Klinefelter syndrome (XXY), are common genetic conditions in humans. The study of individuals with sex chromosome aneuploidies provides a promising framework for studying sexual dimorphism in neurodevelopmental and psychiatric disorders. Here we will review and contrast four syndromes caused by variation in the number of sex chromosomes: Turner syndrome, Klinefelter syndrome, XYY syndrome, and XXX syndrome. Overall we describe an increased rate of attention-deficit hyperactivity disorder and autism spectrum disorder, along with the increased rates of major depressive disorder and anxiety disorders in one or more of these conditions. In addition to contributing unique insights about sexual dimorphism in neuropsychiatric disorders, awareness of the increased risk of neurodevelopmental and psychiatric disorders in sex chromosome aneuploidies can inform appropriate management of these common genetic disorders.

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Section: Adhd In Scasmentioning

confidence: 99%

Sex differences in psychiatric disorders: what we can learn from sex chromosome aneuploidies

Green

Flash

Reiss

2018

Neuropsychopharmacol

130

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“…This drive has led to over 40 genome wide association studies (GWAS) executed over the last decade which have identified approximately 170 common variants to the disease . At the molecular level, these variants can be categorized as hereditary, sporadic or epigenetic, whereby, the latter two can overlap and some noteworthy ones are listed in Table while others are discussed elsewhere …”

Section: Causes For Prostate Cancer Disparitiesmentioning

confidence: 99%

“…75 At the molecular level, these variants can be categorized as hereditary, sporadic or epigenetic, whereby, the latter two can overlap and some noteworthy ones are listed in Table 2 while others are discussed elsewhere. [75][76][77][78][79][80][81][82][83] The common thread observed in these studies is that more than 90% of these investigations are conducted in MEA. As a result, significant strides have been made in the design of serum and urine diagnostic biomarkers, whereby some are currently clinically applicable as mentioned earlier and these were recently reviewed in Sharma et al 86 Some include (a) the noncoding RNA, PCA3 that is believed to be overexpressed in 95% of PCa cases in MEA, 76,86 presents in high levels in some men but is unaccompanied by malignancy meanwhile additional studies confirmed an association of this biomarker in Chinese men 87,88…”

Section: Molecular Studiesmentioning

confidence: 99%

Disparities in prostate cancer incidence and mortality rates: Solvable or not?

et al. 2019

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Prostate cancer (PCa) is recognized as a disease possessing not only great variation in its geographic and racial distribution but also tremendous variation in its potential to cause morbidity and death and it, therefore, ought not to be considered a homogenous disease entity. Morbidity and death from PCa are disproportionately higher in men of African ancestry (MAA) who are generally observed to have more aggressive disease and worse outcomes following treatment compared to men of European ancestry (MEA). The higher rates of PCa among MAA relative to MEA appear to be multifactorial and related to inherent differences in biological aggressiveness; a continued lack of awareness of the disease and methods of prevention; a lower prevalence of screen‐detected PCa; comparatively lower access to quality healthcare as well as systemic and institutionalized disparities in the administration of optimal care to MAA in developed countries such as the United States of America where high‐quality care is available. Even when access to quality healthcare is assured in equal access settings, it appears that MAA still have worse outcomes after PCa treatment stage‐for‐stage and grade‐for‐grade compared to MEA, suggesting that, inherent racial, ethnic and biological differences are paramount in predicting poor outcomes. This review has explored the different contributing factors to the current disparities in PCa incidence and mortality rates with emphasis on the incongruence in how research has been conducted in understanding the disease towards developing therapies.

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“…In recent years, genome-wide association studies (GWAS) have become a powerful strategy for the detection of variation in different traits based on high throughput SNP platforms. It has been widely used in humans (Hindorff et al, 2009 ; Lauc et al, 2010 ; Hoffmann et al, 2017 ) and domestic animals (Petersen et al, 2013 ; Kominakis et al, 2017 ). In pigs, many GWAS have been performed on various economically important traits, including immune traits (Luo et al, 2012 ; Ponsuksili et al, 2016 ), meat quality traits (Casiró et al, 2017 ; Verardo et al, 2017 ), and structural soundness traits (Fan et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Association Study of Piglet Uniformity and Farrowing Interval

et al. 2017

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Piglet uniformity (PU) and farrowing interval (FI) are important reproductive traits related to production and economic profits in the pig industry. However, the genetic architecture of the longitudinal trends of reproductive traits still remains elusive. Herein, we performed a genome-wide association study (GWAS) to detect potential genetic variation and candidate genes underlying the phenotypic records at different parities for PU and FI in a population of 884 Large White pigs. In total, 12 significant SNPs were detected on SSC1, 3, 4, 9, and 14, which collectively explained 1–1.79% of the phenotypic variance for PU from parity 1 to 4, and 2.58–4.11% for FI at different stages. Of these, seven SNPs were located within 16 QTL regions related to swine reproductive traits. One QTL region was associated with birth body weight (related to PU) and contained the peak SNP MARC0040730, and another was associated with plasma FSH concentration (related to FI) and contained the SNP MARC0031325. Finally, some positional candidate genes for PU and FI were identified because of their roles in prenatal skeletal muscle development, fetal energy substrate, pre-implantation, and the expression of mammary gland epithelium. Identification of novel variants and candidate genes will greatly advance our understanding of the genetic mechanisms of PU and FI, and suggest a specific opportunity for improving marker assisted selection or genomic selection in pigs.

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Genome-wide association study of prostate-specific antigen levels identifies novel loci independent of prostate cancer

Cited by 58 publications

References 83 publications

Sex differences in psychiatric disorders: what we can learn from sex chromosome aneuploidies

Sex differences in psychiatric disorders: what we can learn from sex chromosome aneuploidies

Disparities in prostate cancer incidence and mortality rates: Solvable or not?

Genome-Wide Association Study of Piglet Uniformity and Farrowing Interval

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