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Dive into the research topics where Alicia Young is active.

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Featured researches published by Alicia Young.


PLOS Biology | 2013

Generalization and dilution of association results from European GWAS in populations of non-European ancestry: the PAGE study.

Christopher S. Carlson; Tara C. Matise; Kari E. North; Christopher A. Haiman; Megan D. Fesinmeyer; Steven Buyske; Fredrick R. Schumacher; Ulrike Peters; Nora Franceschini; Marylyn D. Ritchie; David Duggan; Kylee L. Spencer; Logan Dumitrescu; Charles B. Eaton; Fridtjof Thomas; Alicia Young; Cara L. Carty; Gerardo Heiss; Loic Le Marchand; Dana C. Crawford; Lucia A. Hindorff; Charles Kooperberg

A multi-ethnic study demonstrates that the extrapolation of genetic disease risk models from European populations to other ethnicities is compromised more strongly by genetic structure than by environmental or global genetic background in differential genetic risk associations across ethnicities.


PLOS ONE | 2012

Evaluation of the Metabochip Genotyping Array in African Americans and Implications for Fine Mapping of GWAS-Identified Loci: The PAGE Study

Steven Buyske; Ying Wu; Cara L. Carty; Iona Cheng; Themistocles L. Assimes; Logan Dumitrescu; Lucia A. Hindorff; Sabrina L. Mitchell; José Luis Ambite; Eric Boerwinkle; Petra Buzkova; Christopher S. Carlson; Barbara Cochran; David Duggan; Charles B. Eaton; Megan D. Fesinmeyer; Nora Franceschini; Jeff Haessler; Nancy S. Jenny; Hyun Min Kang; Charles Kooperberg; Yi Lin; Loic Le Marchand; Tara C. Matise; Jennifer G. Robinson; Carlos J. Rodriguez; Fredrick R. Schumacher; Benjamin F. Voight; Alicia Young; Teri A. Manolio

The Metabochip is a custom genotyping array designed for replication and fine mapping of metabolic, cardiovascular, and anthropometric trait loci and includes low frequency variation content identified from the 1000 Genomes Project. It has 196,725 SNPs concentrated in 257 genomic regions. We evaluated the Metabochip in 5,863 African Americans; 89% of all SNPs passed rigorous quality control with a call rate of 99.9%. Two examples illustrate the value of fine mapping with the Metabochip in African-ancestry populations. At CELSR2/PSRC1/SORT1, we found the strongest associated SNP for LDL-C to be rs12740374 (p = 3.5×10−11), a SNP indistinguishable from multiple SNPs in European ancestry samples due to high correlation. Its distinct signal supports functional studies elsewhere suggesting a causal role in LDL-C. At CETP we found rs17231520, with risk allele frequency 0.07 in African Americans, to be associated with HDL-C (p = 7.2×10−36). This variant is very rare in Europeans and not tagged in common GWAS arrays, but was identified as associated with HDL-C in African Americans in a single-gene study. Our results, one narrowing the risk interval and the other revealing an associated variant not found in Europeans, demonstrate the advantages of high-density genotyping of common and rare variation for fine mapping of trait loci in African American samples.


Journal of Clinical Oncology | 2012

Estrogen Plus Progestin and Colorectal Cancer Incidence and Mortality

Michael S. Simon; Rowan T. Chlebowski; Jean Wactawski-Wende; Karen C. Johnson; Andrew Muskovitz; Ikuko Kato; Alicia Young; F. Allan Hubbell; Ross L. Prentice

PURPOSE During the intervention phase in the Womens Health Initiative (WHI) clinical trial, use of estrogen plus progestin reduced the colorectal cancer diagnosis rate, but the cancers were found at a substantially higher stage. To assess the clinical relevance of the findings, analyses of the influence of combined hormone therapy on colorectal cancer incidence and colorectal cancer mortality were conducted after extended follow-up. PATIENTS AND METHODS The WHI study was a randomized, double-blind, placebo-controlled clinical trial involving 16,608 postmenopausal women with an intact uterus who were randomly assigned to daily 0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate (n = 8,506) or matching placebo (n = 8,102). Colorectal cancer diagnosis rates and colorectal cancer mortality were assessed. RESULTS After a mean of 5.6 years (standard deviation [SD], 1.03 years) of intervention and 11.6 years (SD, 3.1 years) of total follow-up, fewer colorectal cancers were diagnosed in the combined hormone therapy group compared with the placebo group (diagnoses/year, 0.12% v 0.16%; hazard ratio [HR], 0.72; 95% CI, 0.56 to 0.94; P = .014). Bowel screening examinations were comparable between groups throughout. Cancers in the combined hormone therapy group more commonly had positive lymph nodes (50.5% v 28.6%; P < .001) and were at higher stage (regional or distant, 68.8% v 51.4%; P = .003). Although not statistically significant, there was a higher number of colorectal cancer deaths in the combined hormone therapy group (37 v 27 deaths; 0.04% v 0.03%; HR, 1.29; 95% CI, 0.78 to 2.11; P = .320). CONCLUSION The findings, suggestive of diagnostic delay, do not support a clinically meaningful benefit for combined hormone therapy on colorectal cancer.


Genetic Epidemiology | 1997

Comparison of model-free linkage mapping strategies for the study of a complex trait.

Christopher I. Amos; J. Krushkal; Tracy J. Thiel; Alicia Young; D. K. Zhu; Eric Boerwinkle; M. De Andrade

We compared several strategies for identifying and estimating effects from a genetic locus in the etiology of a complex trait. For our analyses we used data from simulated trait 1 and chromosome 5. Results from analysis of the first 20 replicates showed that a components of variance test provided considerably better power for identifying linkage than tests that consider pair differences. We also compared the power from constructing tests with a single marker, an approximate method using five markers jointly, or a multipoint analysis using all 25 markers on chromosome 5 jointly. Results from this analysis showed substantially better power when all markers were jointly used in the analysis. Results from considering all replicates showed that all methods of estimation provided maximal test statistics at the correct marker position, but the components of variance procedure provided more power to detect the correct position than other methods.


The American Journal of Clinical Nutrition | 2011

Prospective association of vitamin D concentrations with mortality in postmenopausal women: results from the Women's Health Initiative (WHI)

Charles B. Eaton; Alicia Young; Matthew A. Allison; Jennifer G. Robinson; Lisa W. Martin; Lewis H. Kuller; Karen C. Johnson; J. David Curb; Linda Van Horn; Anne McTiernan; Simin Liu; JoAnn E. Manson

BACKGROUND Prospective epidemiologic data on the association between vitamin D and all-cause and cause-specific mortality are limited. OBJECTIVE This study aimed to determine whether 25-hydroxyvitamin D [25(OH)D] concentrations were prospectively and independently associated with cardiovascular disease (CVD), cancer, and all-cause mortality in postmenopausal women. DESIGN A substudy in 2429 postmenopausal women within the Womens Health Initiative (WHI) with measured baseline 25(OH)D concentrations were followed for 10 y for death from CVD, cancer, and all-cause mortality. Proportional hazards models were performed to evaluate quartiles of month-adjusted 25(OH)D concentrations, with adjustment for potential confounders. Sequential model building and analysis for multiplicative interaction were performed to evaluate the effects of central adiposity on the association of low 25(OH)D with all-cause mortality. RESULTS Of the 2429 women, 224 deaths occurred, with 79 deaths from CVD and 62 deaths from cancer. Multivariate-adjusted HRs that compared quartiles 1 (lowest) to 4 (highest) of 25(OH)D for all-cause mortality (HR: 1.25; 95% CI: 0.80, 1.95), CVD mortality (HR: 1.27; 95% CI: 0.81, 1.99), and cancer mortality (HR: 1.39; 95% CI: 0.88, 2.19) were not significant. There was a potential interaction (P = 0.08) between abdominal obesity and low 25(OH)D concentrations that showed an increased risk of the lowest quartile of 25(OH)D concentrations (HR: 1.85; 95% CI: 1.00, 3.44) with increased mortality in women with a normal waist circumference but no increased risk in women with abdominal obesity (HR: 0.96; 95% CI: 0.52, 1.76). CONCLUSION Body fat distribution may play an important role in the modulation of the effect of low vitamin D concentrations on health. This trial was registered at clinicaltrials.gov as NCT 00000611.


Human Reproduction | 2013

Replication of genetic loci for ages at menarche and menopause in the multi-ethnic Population Architecture using Genomics and Epidemiology (PAGE) study

Cara L. Carty; Kylee L. Spencer; Veronica Wendy Setiawan; Lindsay Fernández-Rhodes; Jennifer Malinowski; Steven Buyske; Alicia Young; Neal W. Jorgensen; I. Cheng; Christopher S. Carlson; Kristin Brown-Gentry; Robert Goodloe; Amy J. Park; Nisha I. Parikh; Brian E. Henderson; Loic Le Marchand; Jean Wactawski-Wende; Myriam Fornage; Tara C. Matise; Lucia A. Hindorff; A.M. Arnold; Christopher A. Haiman; Nora Franceschini; Ulrike Peters; Dana C. Crawford

STUDY QUESTION Do genetic associations identified in genome-wide association studies (GWAS) of age at menarche (AM) and age at natural menopause (ANM) replicate in women of diverse race/ancestry from the Population Architecture using Genomics and Epidemiology (PAGE) Study? SUMMARY ANSWER We replicated GWAS reproductive trait single nucleotide polymorphisms (SNPs) in our European descent population and found that many SNPs were also associated with AM and ANM in populations of diverse ancestry. WHAT IS KNOWN ALREADY Menarche and menopause mark the reproductive lifespan in women and are important risk factors for chronic diseases including obesity, cardiovascular disease and cancer. Both events are believed to be influenced by environmental and genetic factors, and vary in populations differing by genetic ancestry and geography. Most genetic variants associated with these traits have been identified in GWAS of European-descent populations. STUDY DESIGN, SIZE, DURATION A total of 42 251 women of diverse ancestry from PAGE were included in cross-sectional analyses of AM and ANM. MATERIALS, SETTING, METHODS SNPs previously associated with ANM (n = 5 SNPs) and AM (n = 3 SNPs) in GWAS were genotyped in American Indians, African Americans, Asians, European Americans, Hispanics and Native Hawaiians. To test SNP associations with ANM or AM, we used linear regression models stratified by race/ethnicity and PAGE sub-study. Results were then combined in race-specific fixed effect meta-analyses for each outcome. For replication and generalization analyses, significance was defined at P < 0.01 for ANM analyses and P < 0.017 for AM analyses. MAIN RESULTS AND THE ROLE OF CHANCE We replicated findings for AM SNPs in the LIN28B locus and an intergenic region on 9q31 in European Americans. The LIN28B SNPs (rs314277 and rs314280) were also significantly associated with AM in Asians, but not in other race/ethnicity groups. Linkage disequilibrium (LD) patterns at this locus varied widely among the ancestral groups. With the exception of an intergenic SNP at 13q34, all ANM SNPs replicated in European Americans. Three were significantly associated with ANM in other race/ethnicity populations: rs2153157 (6p24.2/SYCP2L), rs365132 (5q35/UIMC1) and rs16991615 (20p12.3/MCM8). While rs1172822 (19q13/BRSK1) was not significant in the populations of non-European descent, effect sizes showed similar trends. LIMITATIONS, REASONS FOR CAUTION Lack of association for the GWAS SNPs in the non-European American groups may be due to differences in locus LD patterns between these groups and the European-descent populations included in the GWAS discovery studies; and in some cases, lower power may also contribute to non-significant findings. WIDER IMPLICATIONS OF THE FINDINGS The discovery of genetic variants associated with the reproductive traits provides an important opportunity to elucidate the biological mechanisms involved with normal variation and disorders of menarche and menopause. In this study we replicated most, but not all reported SNPs in European descent populations and examined the epidemiologic architecture of these early reported variants, describing their generalizability and effect size across differing ancestral populations. Such data will be increasingly important for prioritizing GWAS SNPs for follow-up in fine-mapping and resequencing studies, as well as in translational research.


The Journal of Pain | 2012

Predictors of Change in Pain and Physical Functioning among Post-Menopausal Women with Recurrent Pain Conditions in the Women’s Health Initiative Observational Cohort

Jennifer Brennan Braden; Alicia Young; Mark D. Sullivan; Brian Walitt; Andrea Z. LaCroix; Lisa W. Martin

UNLABELLED Pain complaints are commonly reported symptoms among postmenopausal women and can have significant effects on health-related quality of life. We sought to identify medical and psychosocial factors that predict changes in pain and overall physical functioning over a 3-year period among postmenopausal women with recurrent pain conditions. We examined data from postmenopausal women age 50 to 79 with recurrent pain conditions (low back pain, neck pain, headache or migraines, or joint pain or stiffness) over a 3-year period using the Womens Health Initiative Observational Study Cohort (N = 67,963). Multinomial logistic regression models controlling for demographic and clinical characteristics were used to identify baseline predictors of change in the SF-36 subscales for pain and physical functioning between baseline and 3-year follow-up. Body mass index (BMI) was associated with worsening of pain (OR [95% CI] 1.54 [1.45-1.63] for BMI ≥30) and physical functioning (1.83 [1.71-1.95] for BMI ≥30). A higher reported number of nonpain symptoms, higher medical comorbidity, and a positive screen for depression (1.13 [1.05-1.22] for worsened pain) were also associated with worsening of pain and physical functioning. Baseline prescription opioid use was also associated with lack of improvement in pain (OR .42, 95% CI .36-.49) and with worsened physical functioning (1.25 [1.04-1.51]). PERSPECTIVE This study presents prospective data on change in pain and physical functioning in postmenopausal women over a 3-year period. Our results suggest depression, nonpain physical symptoms, obesity, and possibly opioid treatment are associated with worse long-term pain outcomes in this population.


PLOS ONE | 2013

Genetic Variation and Reproductive Timing: African American Women from the Population Architecture Using Genomics and Epidemiology (PAGE) Study

Kylee L. Spencer; Jennifer Malinowski; Cara L. Carty; Nora Franceschini; Lindsay Fernández-Rhodes; Alicia Young; Iona Cheng; Marylyn D. Ritchie; Christopher A. Haiman; Lynne R. Wilkens; ChunyuanWu; Tara C. Matise; Christopher S. Carlson; Kathleen Brennan; Amy J. Park; Aleksandar Rajkovic; Lucia A. Hindorff; Steven Buyske; Dana C. Crawford

Age at menarche (AM) and age at natural menopause (ANM) define the boundaries of the reproductive lifespan in women. Their timing is associated with various diseases, including cancer and cardiovascular disease. Genome-wide association studies have identified several genetic variants associated with either AM or ANM in populations of largely European or Asian descent women. The extent to which these associations generalize to diverse populations remains unknown. Therefore, we sought to replicate previously reported AM and ANM findings and to identify novel AM and ANM variants using the Metabochip (n = 161,098 SNPs) in 4,159 and 1,860 African American women, respectively, in the Women’s Health Initiative (WHI) and Atherosclerosis Risk in Communities (ARIC) studies, as part of the Population Architecture using Genomics and Epidemiology (PAGE) Study. We replicated or generalized one previously identified variant for AM, rs1361108/CENPW, and two variants for ANM, rs897798/BRSK1 and rs769450/APOE, to our African American cohort. Overall, generalization of the majority of previously-identified variants for AM and ANM, including LIN28B and MCM8, was not observed in this African American sample. We identified three novel loci associated with ANM that reached significance after multiple testing correction (LDLR rs189596789, p = 5×10−08; KCNQ1 rs79972789, p = 1.9×10−07; COL4A3BP rs181686584, p = 2.9×10−07). Our most significant AM association was upstream of RSF1, a gene implicated in ovarian and breast cancers (rs11604207, p = 1.6×10−06). While most associations were identified in either AM or ANM, we did identify genes suggestively associated with both: PHACTR1 and ARHGAP42. The lack of generalization coupled with the potentially novel associations identified here emphasize the need for additional genetic discovery efforts for AM and ANM in diverse populations.


Journal of the National Cancer Institute | 2014

Pleiotropic Associations of Risk Variants Identified for Other Cancers With Lung Cancer Risk: The PAGE and TRICL Consortia

S. Lani Park; Megan D. Fesinmeyer; Maria Timofeeva; Christian Caberto; Jonathan M. Kocarnik; Younghun Han; Shelly Ann Love; Alicia Young; Logan Dumitrescu; Yi Lin; Robert Goodloe; Lynne R. Wilkens; Lucia A. Hindorff; Jay H. Fowke; Cara L. Carty; Steven Buyske; Frederick R. Schumacher; Anne M. Butler; Holli H. Dilks; Ewa Deelman; Michele L. Cote; Wei Chen; Mala Pande; David C. Christiani; John K. Field; Heike Bickebller; Angela Risch; Joachim Heinrich; Paul Brennan; Yufei Wang

Background Genome-wide association studies have identified hundreds of genetic variants associated with specific cancers. A few of these risk regions have been associated with more than one cancer site; however, a systematic evaluation of the associations between risk variants for other cancers and lung cancer risk has yet to be performed. Methods We included 18023 patients with lung cancer and 60543 control subjects from two consortia, Population Architecture using Genomics and Epidemiology (PAGE) and Transdisciplinary Research in Cancer of the Lung (TRICL). We examined 165 single-nucleotide polymorphisms (SNPs) that were previously associated with at least one of 16 non–lung cancer sites. Study-specific logistic regression results underwent meta-analysis, and associations were also examined by race/ethnicity, histological cell type, sex, and smoking status. A Bonferroni-corrected P value of 2.5×10–5 was used to assign statistical significance. Results The breast cancer SNP LSP1 rs3817198 was associated with an increased risk of lung cancer (odds ratio [OR] = 1.10; 95% confidence interval [CI] = 1.05 to 1.14; P = 2.8×10–6). This association was strongest for women with adenocarcinoma (P = 1.2×10–4) and not statistically significant in men (P = .14) with this cell type (P het by sex = .10). Two glioma risk variants, TERT rs2853676 and CDKN2BAS1 rs4977756, which are located in regions previously associated with lung cancer, were associated with increased risk of adenocarcinoma (OR = 1.16; 95% CI = 1.10 to 1.22; P = 1.1×10–8) and squamous cell carcinoma (OR = 1.13; CI = 1.07 to 1.19; P = 2.5×10–5), respectively. Conclusions Our findings demonstrate a novel pleiotropic association between the breast cancer LSP1 risk region marked by variant rs3817198 and lung cancer risk.


Cancer | 2015

Estrogen and colorectal cancer incidence and mortality

Sayeh Lavasani; Rowan T. Chlebowski; Ross L. Prentice; Ikuko Kato; Jean Wactawski-Wende; Karen C. Johnson; Alicia Young; Rebecca J. Rodabough; F. Allan Hubbell; Ali Mahinbakht; Michael S. Simon

The preponderance of observational studies describe an association between the use of estrogen alone and a lower incidence of colorectal cancer. In contrast, no difference in the incidence of colorectal cancer was seen in the Womens Health Initiative (WHI) randomized, placebo‐controlled trial with estrogen alone after a mean intervention of 7.1 years and cumulative follow‐up of 13.2 years. This study extends these findings by providing detailed analyses of the effects of estrogen alone on the histology, grade, and stage of colorectal cancer, relevant subgroups, and deaths from and after colorectal cancer.

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Cara L. Carty

George Washington University

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Lucia A. Hindorff

National Institutes of Health

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Karen C. Johnson

University of Tennessee Health Science Center

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Ikuko Kato

Wayne State University

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Rowan T. Chlebowski

Los Angeles Biomedical Research Institute

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