Roman Kosoy

Publications (13) View all

• Article: Relationship between Hysterectomy and Admixture in African American Women.

  Lihong Qi, Rami Nassir, Roman Kosoy, Lorena Garcia, L Elaine Waetjen, Heather M Ochs-Balcom, Margery Gass, John Robbins, Michael F Seldin
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  ABSTRACT: OBJECTIVE: Most studies suggest that hysterectomies are more common in African Americans than in other ethnic groups. To assess this ethnic surgical disparity in a novel way, our main goal was to determine whether admixture (the proportion of sub-Saharan African or European origin in individuals) is associated with hysterectomy frequency in African American women in the Women's Health Initiative (WHI). STUDY DESIGN: In this retrospective study, we used ancestry informative single nucleotide polymorphisms (SNPs) to estimate admixture proportions in >10,000 African American women from the WHI. Logistic regression models were used to assess the association between admixture and self-reported history of hysterectomy with and without controlling for relevant covariates. Multinomial logistic regression models were used to assess the association between admixture and self-reported age of hysterectomy. We also considered other potential risk factors (adiposity, hypertension, and education) for hysterectomy accounting for admixture. RESULTS: African admixture was a strong risk factor after adjusting for multiple covariates (OR 1.85, P<.0001). The admixture risk for hysterectomy was highest for those performed in the 35-39 age range (OR 3.08, P<.0001) and least evident in oldest ages (45 or older). Our analyses also suggest that adiposity, hypertension and education were independently associated with hysterectomy in this population group. CONCLUSION: These results suggest that higher African admixture is associated with higher frequencies of hysterectomy and that genetic studies specifically targeting African American women and diseases associated with hysterectomy may be especially useful in understanding the pathogenesis and underlying cause of this disparity in health outcome.
  American journal of obstetrics and gynecology 01/2013; · 3.28 Impact Factor
• Article: Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants.

  Brian D Juran, Gideon M Hirschfield, Pietro Invernizzi, Elizabeth J Atkinson, Yafang Li, Gang Xie, Roman Kosoy, Michael Ransom, Ye Sun, Ilaria Bianchi, [......], Cynthia Levy, Andre Franke, Peter K Gregersen, Fabrizio Bossa, M Eric Gershwin, Mariza Deandrade, Christopher I Amos, Konstantinos N Lazaridis, Michael F Seldin, Katherine A Siminovitch
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  ABSTRACT: To further characterize the genetic basis of primary biliary cirrhosis (PBC), we genotyped 2426 PBC patients and 5731 unaffected controls from three independent cohorts using a single nucleotide polymorphism (SNP) array (Immunochip) enriched for autoimmune disease risk loci. Meta-analysis of the genotype data sets identified a novel disease-associated locus near the TNFSF11 gene at 13q14, provided evidence for association at six additional immune-related loci not previously implicated in PBC and confirmed associations at 19 of 22 established risk loci. Results of conditional analyses also provided evidence for multiple independent association signals at four risk loci, with haplotype analyses suggesting independent SNP effects at the 2q32 and 16p13 loci, but complex haplotype driven effects at the 3q25 and 6p21 loci. By imputing classical HLA alleles from this data set, four class II alleles independently contributing to the association signal from this region were identified. Imputation of genotypes at the non-HLA loci also provided additional associations, but none with stronger effects than the genotyped variants. An epistatic interaction between the IL12RB2 risk locus at 1p31and the IRF5 risk locus at 7q32 was also identified and suggests a complementary effect of these loci in predisposing to disease. These data expand the repertoire of genes with potential roles in PBC pathogenesis that need to be explored by follow-up biological studies.
  Human Molecular Genetics 08/2012; · 7.64 Impact Factor
• Article: Relationship between gallbladder surgery and ethnic admixture in African American and Hispanic American women.

  Rami Nassir, Lihong Qi, Roman Kosoy, Lorena Garcia, John Robbins, Michael F Seldin
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  ABSTRACT: The objective of this study was to investigate whether differences in admixture in African American and Hispanic American adult women are associated with differences in gallbladder surgery. Gallbladder surgery history on entry to the Women's Health Initiative's (WHI) study was used as a dichotomous outcome measure for this study. The proportion of European, sub-Saharan African, and Amerindian (AMI) admixture was estimated for 10,841 African American and 4,620 Hispanic American women in WHI using 92 ancestry informative markers. Logistic regression analyses assessed the relationship between admixture and gallbladder surgery in WHI women (enrollment at ages >50, mean age 61 years) with or without adjusting for multiple covariates, including measures of adiposity, parity, alcohol use, and education. There was a significant positive association between AMI admixture and the frequency of gallbladder surgery in Hispanic Americans. The odds ratio (OR) and 95% confidence intervals (CIs) for AMI admixture group was OR=2.97, CI=2.01-4.38, P<10(-4). Although there were strong positive associations with parity and adiposity, and negative associations with alcohol consumption and education, accounting for these covariates did not remove the admixture association (OR=2.46, CI=1.62-3.73). In contrast, the effect of African admixture was nearly indistinguishable from that of the European admixture, both of which were protective in the Hispanic American group, and African admixture had a marginal association with decreased gallbladder surgery in the African American group. Measures of adiposity were associated with increased risk for gallbladder surgery and remained significant after accounting for admixture and each of the other covariates. Education level and alcohol use were associated with decreased risk for gallbladder disease. However, after accounting for the other covariates these variably remained significant. AMI admixture is strongly associated with gallbladder surgery in women, even after adjustment for selected risk factors for cholelithiasis. Additional studies to ascertain the specific genetic risk factors underlying these associations are warranted.
  The American Journal of Gastroenterology 03/2012; 107(6):932-40. · 7.28 Impact Factor
• Article: Genome-wide association study identifies novel loci predisposing to cutaneous melanoma.

  Christopher I Amos, Li-E Wang, Jeffrey E Lee, Jeffrey E Gershenwald, Wei V Chen, Shenying Fang, Roman Kosoy, Mingfeng Zhang, Abrar A Qureshi, Selina Vattathil, [......], Yaji Xu, Younghun Han, Kaiyan Jing, Caitlin McHugh, Cathy C Laurie, Kim F Doheny, Elizabeth W Pugh, Michael F Seldin, Jiali Han, Qingyi Wei
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  ABSTRACT: We performed a multistage genome-wide association study of melanoma. In a discovery cohort of 1804 melanoma cases and 1026 controls, we identified loci at chromosomes 15q13.1 (HERC2/OCA2 region) and 16q24.3 (MC1R) regions that reached genome-wide significance within this study and also found strong evidence for genetic effects on susceptibility to melanoma from markers on chromosome 9p21.3 in the p16/ARF region and on chromosome 1q21.3 (ARNT/LASS2/ANXA9 region). The most significant single-nucleotide polymorphisms (SNPs) in the 15q13.1 locus (rs1129038 and rs12913832) lie within a genomic region that has profound effects on eye and skin color; notably, 50% of variability in eye color is associated with variation in the SNP rs12913832. Because eye and skin colors vary across European populations, we further evaluated the associations of the significant SNPs after carefully adjusting for European substructure. We also evaluated the top 10 most significant SNPs by using data from three other genome-wide scans. Additional in silico data provided replication of the findings from the most significant region on chromosome 1q21.3 rs7412746 (P = 6 × 10(-10)). Together, these data identified several candidate genes for additional studies to identify causal variants predisposing to increased risk for developing melanoma.
  Human Molecular Genetics 09/2011; 20(24):5012-23. · 7.64 Impact Factor
• Article: Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis.

  Xiangdong Liu, Pietro Invernizzi, Yue Lu, Roman Kosoy, Yan Lu, Ilaria Bianchi, Mauro Podda, Chun Xu, Gang Xie, Fabio Macciardi, [......], Agostino Colli, Giancarlo Spinzi, Renzo Montanari, Peter K Gregersen, E Jenny Heathcote, Gideon M Hirschfield, Katherine A Siminovitch, Christopher I Amos, M Eric Gershwin, Michael F Seldin
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  ABSTRACT: A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 x 10(-11), odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 x 10(-10), OR = 1.63) and 17q12-21 (P = 1.7 x 10(-10), OR = 1.38).
  Nature Genetics 08/2010; 42(8):658-60. · 35.53 Impact Factor