Richard M Cawthon

University of Utah, Salt Lake City, Utah, United States

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Publications (81)519.54 Total impact

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    Mitchell J Machiela · Chao Agnes Hsiung · Xiao-Ou Shu · Wei Jie Seow · Zhaoming Wang · Keitaro Matsuo · Yun-Chul Hong · Adeline Seow · Chen Wu · H Dean Hosgood · [...] · Yi-Long Wu · Pan-Chyr Yang · Baosen Zhou · Min-Ho Shin · Joseph F Fraumeni Jr · Wei Zheng · Dongxin Lin · Stephen J Chanock · Nathaniel Rothman · Qing Lan
  • International Journal of Epidemiology 09/2015; DOI:10.1093/ije/dyv169 · 9.18 Impact Factor
  • International Journal of Epidemiology 09/2015; DOI:10.1093/ije/dyv170 · 9.18 Impact Factor
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    ABSTRACT: Atrial fibrillation (AF) diminishes quality of life and accounts for approximately one-third of all strokes. Studies have associated mitochondrial dysfunction with both AF and telomere length (TL). We hypothesized a relationship between AF and TL. Blood was collected from consenting participants in the Intermountain Heart Collaborative Study (n=3576) and DNA extracted. TL was determined by multiplex quantitative PCR and normalized to a single copy gene and reported as telomere/single gene ratio (t/s). Patient information was extracted from Intermountain Healthcare's electronic records database; prevalent AF was determined by discharge ICD-9 code; AF subtype [paroxysmal(Px), persistent (Ps), long-standing persistent/permanent (Pm)] determined by chart review. t/s decreased with age (p<0.00001). Subjects with a history of AF (n=379, 10.6%) had shorter telomeres (mean t/s ± SD =0.87 ± 0.29) compared to subjects without AF (mean t/s =0.95 ± 0.32, p<0.0001). The association remained after adjustment for age (p=0.017) and cardiovascular risk factors (p=0.016). AF subtype was determined for 277 subjects; 110 (39.7%) had Px AF, 65 (23.5%) Ps, and 102 (36.8%) Pm AF. Mean t/s did not differ between Ps, Pm and subjects without AF (0.94 ± 0.40, 0.94 ± 0.27, and 0.95 ± 0.32, respectively). However, for Px, the mean t/s Px (0.81 ± 0.22) was significantly shorter than for Ps (p=0.026), Pm (p=0.004) or subjects without AF (p<0.0001). The present study supports an association between Px AF and TL. Short TL may be a previously unrecognized risk factor for AF with potential applications in diagnosis and therapy. Copyright © 2015. Published by Elsevier Inc.
    Heart rhythm: the official journal of the Heart Rhythm Society 07/2015; DOI:10.1016/j.hrthm.2015.07.032 · 5.08 Impact Factor
  • Journal of the American College of Cardiology 03/2015; 65(10):A64. DOI:10.1016/S0735-1097(15)60064-X · 16.50 Impact Factor
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    ABSTRACT: Recent evidence from several relatively small nested case-control studies in prospective cohorts shows an association between longer telomere length measured phenotypically in peripheral white blood cell (WBC) DNA and increased lung cancer risk. We sought to further explore this relationship by examining a panel of 7 telomere-length associated genetic variants in a large study of 5,457 never-smoking female Asian lung cancer cases and 4,493 never-smoking female Asian controls using data from a previously reported genome-wide association study. Using a group of 1,536 individuals with phenotypically measured telomere length in WBCs in the prospective Shanghai Women's Health study, we demonstrated the utility of a genetic risk score (GRS) of 7 telomere-length associated variants to predict telomere length in an Asian population. We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI=1.34-1.69) for upper vs. lower quartile of the weighted GRS, P-value=4.54 × 10(-14) ) even after removing rs2736100 (P-value=4.81 × 10(-3) ), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies. Stratified analyses suggested the effect of the telomere-associated GRS is strongest among younger individuals. We found no difference in GRS effect between adenocarcinoma and squamous cell subtypes. Our results indicate that a genetic background that favors longer telomere length may increase lung cancer risk, which is consistent with earlier prospective studies relating longer telomere length with increased lung cancer risk. This article is protected by copyright. All rights reserved. © 2014 UICC.
    International Journal of Cancer 12/2014; DOI:10.1002/ijc.29393 · 5.09 Impact Factor
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    ABSTRACT: Exposure to benzene, a known leukemogen and probable lymphomagen, has been demonstrated to result in oxidative stress, which has previously been associated with altered telomere length (TL). TL specifically has been associated with several health outcomes in epidemiologic studies, including cancer risk, and has been demonstrated to be altered following exposure to a variety of chemical agents. To evaluate the association between benzene exposure and TL, we measured TL by monochrome multiplex quantitative PCR in 43 workers exposed to high levels of benzene and 43 age and sex-matched unexposed workers in Shanghai, China. Benzene exposure levels were monitored using organic vapor passive dosimetry badges before phlebotomy. The median benzene exposure level in exposed workers was 31 ppm. The mean TL in controls, workers exposed to levels of benzene below the median (≤31 ppm), and above the median (>31 ppm) was 1.26 ± 0.17, 1.25 ± 0.16, and 1.37 ± 0.23, respectively. Mean TL was significantly elevated in workers exposed to >31 ppm of benzene compared with controls (P = 0.03). Our findings provide evidence that high levels of occupational benzene exposure are associated with TL. Environ. Mol. Mutagen., 2014. Published [2014]. This article is a U.S. Government work and is in the public domain in the USA.
    Environmental and Molecular Mutagenesis 10/2014; 55(8). DOI:10.1002/em.21880 · 2.63 Impact Factor
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    ABSTRACT: Background: Telomere length is a putative biomarker of ageing, morbidity and mortality. Its application is hampered by lack of widely applicable reference ranges and uncertainty regarding the present limits of measurement reproducibility within and between laboratories. Methods: We instigated an international collaborative study of telomere length assessment: 10 different laboratories, employing 3 different techniques [Southern blotting, single telomere length analysis (STELA) and real-time quantitative PCR (qPCR)] performed two rounds of fully blinded measurements on 10 human DNA samples per round to enable unbiased assessment of intra- and inter-batch variation between laboratories and techniques. Results: Absolute results from different laboratories differed widely and could thus not be compared directly, but rankings of relative telomere lengths were highly correlated (correlation coefficients of 0.63-0.99). Intra-technique correlations were similar for Southern blotting and qPCR and were stronger than inter-technique ones. However, inter-laboratory coefficients of variation (CVs) averaged about 10% for Southern blotting and STELA and more than 20% for qPCR. This difference was compensated for by a higher dynamic range for the qPCR method as shown by equal variance after z-scoring. Technical variation per laboratory, measured as median of intra- and inter-batch CVs, ranged from 1.4% to 9.5%, with differences between laboratories only marginally significant (P = 0.06). Gel-based and PCR-based techniques were not different in accuracy. Conclusions: Intra- and inter-laboratory technical variation severely limits the usefulness of data pooling and excludes sharing of reference ranges between laboratories. We propose to establish a common set of physical telomere length standards to improve comparability of telomere length estimates between laboratories.
    International Journal of Epidemiology 09/2014; DOI:10.1093/ije/dyu191 · 9.18 Impact Factor
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    ABSTRACT: Objective: Social control in the health domain refers to attempts by social network members to get an individual to modify their health behaviors. According to the dual effects model of social control, having one's health behavior controlled by others should be related to healthier behavioral change, but might arouse psychological distress as one may resent being controlled. Despite potential healthy behavior change, the stress of social control may thus be detrimental as interpersonal stress has been related to negative health outcomes. In the present study, the association between perceived social control and telomere length was tested to examine its association to biological outcomes. Method: In this cross-sectional study, a relatively healthy community sample of 140 middle age and older adults completed measures of perceived social control, perceived stress, and health behaviors. Peripheral blood mononuclear cells were used to determine telomere length. Results: Main results showed that higher levels of perceived direct social network control were associated with shorter telomere length. These links were not influenced by statistical controls for medication use, self-rated health, trait hostility, and optimism. Perceived social control was also related to greater perceived stress but not health behaviors overall. However, neither perceived stress nor health behaviors mediated the link between social control and telomere length. Conclusions: Although the study design precludes strong inferences, these results suggest that perceived social control may be associated with cellular aging. These data also highlight the utility of integrating biological outcomes into social control models. (PsycINFO Database Record
    Health Psychology 08/2014; 34(5). DOI:10.1037/hea0000148 · 3.59 Impact Factor
  • Justin Tackney · Richard M. Cawthon · James E. Coxworth · Kristen Hawkes
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    ABSTRACT: Objectives Slower rates of aging distinguish humans from our nearest living cousins. Chimpanzees rarely survive their forties while large fractions of women are postmenopausal even in high-mortality hunter–gatherer populations. Cellular and molecular mechanisms for these somatic aging differences remain to be identified, though telomeres might play a role. To find out, we compared telomere lengths across age-matched samples of female chimpanzees and women.Methods We used a monochrome multiplex quantitative polymerase chain reaction to assay canonical telomere repeats in blood cells from captive female chimpanzees (65 individuals; age: 6.2–56.7 years) and compared them to the same measure in human females (43 individuals; age: 7.4–57.3 years).ResultsOur samples showed little difference in attrition rates between the species (∼0.022 T/S per year for chimpanzees and ∼0.012 T/S per year for humans with overlapping 95% confidence intervals), but telomeres were twice as long in chimpanzees as in humans (T/S ratios = 2.70 and 1.26, respectively).Conclusions Based on the longevity differences, we initially hypothesized that telomere shortening rates would be faster in chimpanzees than in humans. Instead, it is shorter telomere length that appears to be the derived state in humans. This comparison indicates that better characterization of physiological aging in our closest living relatives will be indispensable for understanding the evolution of distinctive human longevity. Am. J. Hum. Biol., 2014. © 2014 Wiley Periodicals, Inc.
    American Journal of Human Biology 07/2014; 26(4). DOI:10.1002/ajhb.22538 · 1.70 Impact Factor
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    ABSTRACT: Background The mitochondria are essential organelles and are the location of cellular respiration, which is responsible for the majority of ATP production. Each cell contains multiple mitochondria, and each mitochondrion contains multiple copies of its own circular genome. The ratio of mitochondrial genomes to nuclear genomes is referred to as mitochondrial copy number. Decreases in mitochondrial copy number are known to occur in many tissues as people age, and in certain diseases. The regulation of mitochondrial copy number by nuclear genes has been studied extensively. While mitochondrial variation has been associated with longevity and some of the diseases known to have reduced mitochondrial copy number, the role that the mitochondrial genome itself has in regulating mitochondrial copy number remains poorly understood. Results We analyzed the complete mitochondrial genomes from 1007 individuals randomly selected from the Cache County Study on Memory Health and Aging utilizing the inferred evolutionary history of the mitochondrial haplotypes present in our dataset to identify sequence variation and mitochondrial haplotypes associated with changes in mitochondrial copy number. Three variants belonging to mitochondrial haplogroups U5A1 and T2 were significantly associated with higher mitochondrial copy number in our dataset. Conclusions We identified three variants associated with higher mitochondrial copy number and suggest several hypotheses for how these variants influence mitochondrial copy number by interacting with known regulators of mitochondrial copy number. Our results are the first to report sequence variation in the mitochondrial genome that causes changes in mitochondrial copy number. The identification of these variants that increase mtDNA copy number has important implications in understanding the pathological processes that underlie these phenotypes.
    BMC Bioinformatics 05/2014; 15(Suppl 7):S6. DOI:10.1186/1471-2105-15-S7-S6 · 2.58 Impact Factor
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    ABSTRACT: We investigated the relationship between telomere length and lung cancer in a pooled analysis from three prospective cohort studies: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, conducted among men and women in the United States, and previously published data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) trial conducted among male smokers in Finland, and the Shanghai Women's Health Study (SWHS), which is comprised primarily of never-smokers. The pooled population included 847 cases and 847 controls matched by study, age, and sex. Leukocyte telomere length was measured by a monochrome multiplex quantitative PCR assay. We used conditional logistic regression models to calculate odds ratios (OR) and their 95% confidence intervals (CI) for the association between telomere length and lung cancer risk, adjusted for age and pack-years of smoking. Longer telomere length was associated with increased lung cancer risk in the pooled analysis (OR(95% CI) by quartile: 1.00; 1.24(0.90-1.71); 1.27(0.91-1.78); and 1.86(1.33-2.62); P-trend=0.000022). Findings were consistent across the three cohorts and strongest for subjects with very long telomere length, i.e., lung cancer risks for telomere length (OR(95% CI)) in the upper half of the fourth quartile were 2.41(1.28-4.52), 2.16(1.11-4.23) and 3.02(1.39-6.58) for the PLCO trial, the ATBC trial, and the SWHS, respectively. In addition, the association persisted among cases diagnosed more than six years after blood collection and was particularly evident for female adenocarcinoma cases. Telomere length in white blood cell DNA may be a biomarker of future increased risk of lung cancer in diverse populations.
    Cancer Research 05/2014; 74(15). DOI:10.1158/0008-5472.CAN-14-0459 · 9.33 Impact Factor
  • Cancer Epidemiology Biomarkers & Prevention 05/2014; 23(6). DOI:10.1158/1055-9965.EPI-14-0145 · 4.13 Impact Factor
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    ABSTRACT: Telomeres play an essential role in maintaining chromosomal integrity in the face of physiological stressors. Although, the age-related shortening of telomere length (TL) in highly proliferative tissue, is predominantly due to the replication process, the mechanism for telomere shortening in skeletal muscle, which is minimally proliferative, is unclear. By studying TL in both the upper and lower limbs of the young (Y), old-mobile (OM), and old-immobile (OI) and by virtue of the bipedal nature of human locomotion, which declines with age, it may be possible to elucidate the mechanism responsible for cellular aging of skeletal muscle. With this approach, we revealed that TL (~15 kb) in arm skeletal muscle is unaffected by age. In contrast TL fell progressively in the legs across the young (~15 kb), the old mobile (~13 kb), and old immobile (~11 kb). Interestingly, there was a reciprocal rise in leg muscle free radical across these groups that was correlated with TL (r=0.7), with no such relationship in the arm (r=0.09). Our results document that chronologic age, per se, does not affect cellular aging of skeletal muscle, but reveals that physical inactivity, likely mediated by free radicals, has a profound effect upon this process.
    Clinical Science 04/2014; 127(5-6). DOI:10.1042/CS20140051 · 5.60 Impact Factor
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    Journal of the American College of Cardiology 04/2014; 63(12):A461. DOI:10.1016/S0735-1097(14)60461-7 · 16.50 Impact Factor
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    ABSTRACT: Telomere shortening in arteries could lead to telomere uncapping and cellular senescence, which in turn could promote the development of hypertension. To assess the novel role of arterial telomere dysfunction in hypertension, we compared mean telomere length (qPCR), telomere uncapping (serine 139 phosphorylated histone γ-H2A.X (γ-H2) localized to telomeres: ChIP), and tumor suppressor protein p53 (P53)/cyclin-dependent kinase inhibitor 1A (P21)-induced senescence (P53 bound to P21 gene promoter: ChIP) in arteries from 55 age-matched hypertensive and nonhypertensive individuals. Arterial mean telomere length was not different in hypertensive patients compared with nonhypertensive individuals (P = 0.29). Arterial telomere uncapping and P53/P21-induced senescence were two-fold greater in hypertensive patients compared with nonhypertensive individuals (P = 0.04 and P = 0.02, respectively). Arterial mean telomere length was not associated with telomere uncapping or P53/P21-induced senescence (r = -0.02, P = 0.44 and r = 0.01, P = 0.50, respectively), but telomere uncapping was a highly influential covariate for the hypertension group difference in P53/P21-induced senescence (r = 0.62, P < 0.001, ηp = 0.35). Finally, telomere uncapping was a significant predictor of hypertension status (P = 0.03), whereas mean telomere length was not (P = 0.68). Collectively, these findings demonstrate that arterial telomere uncapping and P53/P21-induced senescence are linked to hypertension independently of mean telomere length, and telomere uncapping influences hypertension status more than mean telomere length.
    Journal of Hypertension 03/2014; 32(6). DOI:10.1097/HJH.0000000000000157 · 4.72 Impact Factor
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    ABSTRACT: To examine whether subjective sleep quality and sleep duration moderate the association between age and telomere length (TL). Participants completed a demographic and sleep quality questionnaire, followed by a blood draw. Social Neuroscience Laboratory. One hundred fifty-four middle-aged to older adults (age 45-77 y) participated. Participants were excluded if they were on immunosuppressive treatment and/or had a disease with a clear immunologic (e.g., cancer) component. N/A. Subjective sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index (PSQI) and TL was determined using peripheral blood mononuclear cells (PBMCs). There was a significant first-order negative association between age and TL. Age was also negatively associated with the self-reported sleep quality item and sleep duration component of the PSQI. A significant age × self-reported sleep quality interaction revealed that age was more strongly related to TL among poor sleepers, and that good sleep quality attenuated the association between age and TL. Moreover, adequate subjective sleep duration among older adults (i.e. greater than 7 h per night) was associated with TL comparable to that in middle-aged adults, whereas sleep duration was unrelated to TL for the middle-aged adults in our study. The current study provides evidence for an association between sleep quality, sleep duration, and cellular aging. Among older adults, better subjective sleep quality was associated with the extent of cellular aging, suggesting that sleep duration and sleep quality may be added to a growing list of modifiable behaviors associated with the adverse effects of aging. Cribbet MR; Carlisle M; Cawthon RM; Uchino BN; Williams PG; Smith TW; Gunn HE; Light KC. Cellular aging and restorative processes: subjective sleep quality and duration moderate the association between age and telomere length in a sample of middle-aged and older adults. SLEEP 2014;37(1):65-70.
    Sleep 01/2014; 37(1):65-70. DOI:10.5665/sleep.3308 · 4.59 Impact Factor
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    ABSTRACT: Human age-dependent telomere attrition and telomere shortening are associated with several age-associated diseases and poorer overall survival. The aim of this study was to determine longitudinal leukocyte telomere length dynamics and identify factors associated with temporal changes in telomere length. Leukocyte telomere length was measured by quantitative polymerase chain reaction in 8074 participants from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study, an ongoing community-based prospective cohort study initiated in 1997. Follow-up data were available at two time points up to 2007. Leukocyte telomere length was measured, on between one and three separate occasions, in a total of 16,783 DNA samples. Multilevel growth models were created to identify the factors that influence leukocyte telomere dynamics. We observed an average attrition rate of 0.47±0.16 relative telomere length units (RTLUs) per year in the study population aged 48 (range 39 to 60) years at baseline. Annual telomere attrition rate increased with age (P < 0.001), and was faster on average in men than in women (P for interaction 0.043). The major independent factors determining telomere attrition rate were active smoking (approximately tripled the loss of RTLU per year, P < 0.0001) and multiple traits of the metabolic syndrome (waist-hip ratio, P = 0.007; blood glucose level, P = 0.045; and HDL cholesterol level, P < 0.001). Smoking and variables linked to the metabolic syndrome are modifiable lifestyle factors that accelerate telomere attrition in humans. The higher rate of cellular ageing may mediate the link between smoking and the metabolic syndrome to an increased risk of several age-associated diseases. This article is protected by copyright. All rights reserved.
    Journal of Internal Medicine 10/2013; 275(2). DOI:10.1111/joim.12149 · 6.06 Impact Factor
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    ABSTRACT: Smoking and diabetes, consistent risk factors for pancreatic cancer, are also factors that influence telomere length maintenance. To test whether telomere length is associated with pancreatic cancer risk, we conducted a nested case-control study in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort of male smokers, aged 50-69 years at baseline. Between 1992 and 2004, 193 incident cases of pancreatic adenocarcinoma occurred (mean follow-up from blood draw: 6.3 years) among participants with whole blood samples available for telomere length assays. For these cases and 660 controls, we calculated odds ratios (OR) and 95% confidence intervals using unconditional logistic regression, adjusting for age, number of years smoked regularly, and history of diabetes mellitus. Telomere length was categorized into quartiles (shortest to longest) and analyzed as both a categorical and a continuous normal variable (reported per 0.2 unit increase in telomere length). All statistical tests were two-sided. Longer telomere length was significantly associated with increased pancreatic cancer risk (continuous OR=1.26 95% CI=1.09-1.46; highest quartile compared to lowest, OR=1.57, 95% CI=1.01-2.43, p-trend=0.007). This association remained for subjects diagnosed within the first five years of blood draw(continuous OR=1.46, 95% CI=1.19-1.79 highest quartile OR=2.92, 95%CI=1.47-5.77, p-trend=0.002), but not those diagnosed greater than five years after blood draw (continuous OR=1.03, 95%CI=0.85-1.22; highest quartile OR=1.04, 95%CI=0.60-1.79). This is the first prospective study to suggest an association between longer blood leukocyte telomere length and increased pancreatic cancer risk. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 08/2013; 133(11). DOI:10.1002/ijc.28272 · 5.09 Impact Factor

Publication Stats

5k Citations
519.54 Total Impact Points


  • 2001–2015
    • University of Utah
      • • Department of Human Genetics
      • • Division of Cardiovascular Genetics
      • • Division of Genetic Epidemiology
      Salt Lake City, Utah, United States
  • 2013
    • Herlev Hospital
      Herlev, Capital Region, Denmark
  • 2011
    • Sapienza University of Rome
      Roma, Latium, Italy
  • 2005–2009
    • University of California, San Francisco
      San Francisco, California, United States