Biology subjects

Sam S Oh

Publications and source records attributed to Sam S Oh.

4 recordsLinked to original sources

bioRxiv2016

The Effects of Migration and Assortative Mating on Admixture Linkage Disequilibrium

1Statistical models in medical and population genetics typically assume that individuals assort randomly in a population. While this simplifies model complexity, it contradicts an increasing body of evidence of non-random mating in human populations. Specifically, it has been shown that assortative mating is significantly affected by genomic ancestry. In this work we examine the effects of ancestry-assortative mating on the linkage disequilibrium between local ancestry tracks of individuals in an admixed population. To accomplish this, we develop an extension to the Wright-Fisher model that allows for ancestry based assortative mating. We show that ancestry-assortment perturbs the distribution of local ancestry linkage disequilibrium (LAD) and the variance of ancestry in a population as a function of the number of generations since admixture. This assortment effect can induce errors in demographic inference of admixed populations when methods assume random mating. We derive closed form formulae for LAD under an assortative-mating model with and without migration. We observe that LAD depends on the correlation of global ancestry of couples in each generation, the migration rate of each of the ancestral populations, the initial proportions of ancestral populations, and the number of generations since admixture. We also present the first evidence of ancestry-assortment in African Americans and examine LAD in simulated and real admixed population data of African Americans. We find that demographic inference under the assumption of random mating significantly underestimates the number of generations since admixture, and that accounting for assortative mating using the patterns of LAD results in estimates that more closely agrees with the historical narrative.

Genetics↗

bioRxiv2016

Novel Genetic Risk factors for Asthma in African American Children: Precision Medicine and The SAGE II Study.

BackgroundAsthma, an inflammatory disorder of the airways, is the most common chronic disease of children worldwide. There are significant racial/ethnic disparities in asthma prevalence, morbidity and mortality among U.S. children. This trend is mirrored in obesity, which may share genetic and environmental risk factors with asthma. The majority of asthma biomedical research has been performed in populations of European decent.\n\nObjectiveWe sought to identify genetic risk factors for asthma in African American children. We also assessed the generalizability of genetic variants associated with asthma in European and Asian populations to African American children.\n\nMethodsOur study population consisted of 1227 (812 asthma cases, 415 controls) African American children with genome-wide single nucleotide polymorphism (SNP) data. Logistic regression was used to identify associations between SNP genotype and asthma status.\n\nResultsWe identified a novel variant in the PTCHD3 gene that is significantly associated with asthma (rs660498, p = 2.2 x10-7) independent of obesity status. Fewer than 5% of previously reported asthma genetic associations identified in European populations replicated in African Americans.\n\nConclusionsOur identification of novel variants associated with asthma in African American children, coupled with our inability to replicate the majority of findings reported in European Americans, underscores the necessity for including diverse populations in biomedical studies of asthma.

Genetics↗

bioRxiv2016

Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures

In clinical practice and biomedical research populations are often divided categorically into distinct racial/ethnic groups. In reality, these categories, which are based on social rather than biological constructs, comprise diverse groups with highly heterogeneous histories, cultures, traditions, religions, social and environmental exposures and ancestral backgrounds. Their use is thus widely debated and genetic ancestry has been suggested as a complement or alternative to this categorization. However, few studies have examined the relative contributions of racial/ethnic identity, genetic ancestry, and environmental exposures on well-established and fundamental biological processes. We examined the associations between ethnicity, ancestry, and environmental exposures and DNA methylation. We typed over 450,000 CpG sites in primary whole blood of 573 individuals of diverse Hispanic descent who also had high-density genotype data. We found that both self-identified ethnicity and genetically determined ancestry were significantly associated with methylation levels at a large number of CpG sites (916 and 194, respectively). Among loci differentially methylated between ethnic groups, a median of 75.7% (IQR 45.8% to 92%) of the variance in methylation associated with ethnicity could be accounted for by shared genomic ancestry accounts. We also found significant enrichment (p = 4.2 x 10-64) of ethnicity-associated sites amongst loci previously associated with environmental and social exposures, particularly maternal smoking during pregnancy. Our study suggests that although differential methylation between ethnic groups can be partially explained by the shared genetic ancestry, a significant effect of ethnicity is likely due to environmental, social, or cultural factors, which differ between ethnic groups.\n\nOne Sentence SummaryIn order to better understand the role of ethnic self-identification and genetically determined ancestry in biomedical outcomes, we explore their relative contributions to variation in methylation, a fundamental biological process.\n\nSources of FundingThis research was supported in part by the Sandler Family Foundation, the American Asthma Foundation, National Institutes of Health (P60 MD006902, R01 HL117004, R21ES24844, U54MD009523, R01 ES015794, R01 HL088133, M01 RR000083, R01 HL078885, R01 HL104608, U19 AI077439, M01 RR00188, U01 HG009080, and R01 HL135156), ARRA grant RC2 HL101651, and TRDRP 24RT-0025; EGB was supported in part through grants from the Flight Attendant Medical Research Institute (FAMRI), and NIH (K23 HL004464); NZ was supported in part by an NIH career development award from the NHLBI (K25HL121295). JMG was supported in part by NIH Training Grant T32 (T32GM007546) and career development awards from the NHLBI (K23HL111636) and NCATS (KL2TR000143) as well as the Hewett Fellowship; N.T. was supported in part by an institutional training grant from the NIGMS (T32-GM007546) and career development awards from the NHLBI (K12-HL119997 and K23-HL125551), Parker B. Francis Fellowship Program, and the American Thoracic Society; CRG was supported in part by NIH Training Grant T32 (GM007175) and the UCSF Chancellors Research Fellowship and Dissertation Year Fellowship; RK was supported with a career development award from the NHLBI (K23HL093023); HJF was supported in part by the GCRC (RR00188); PCA was supported in part by the Ernest S. Bazley Grant; MAS was supported in part by 1R01HL128439-01. This publication was supported by various institutes within the National Institutes of Health. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

Genetics↗

bioRxiv2015

Diversity in Clinical and Biomedical Research: A Promise Yet to Be Fulfilled

Summary PointsO_LIHealth disparities persist across race/ethnicity for the majority of Healthy People 2010 health indicators.\nC_LIO_LIMost physicians and scientists are informed by research extrapolated from a largely homogenous population, usually White and male.\nC_LIO_LIA growing proportion of Americans are not fully benefiting from clinical and biomedical advances since racial and ethnic minorities make up nearly 40% of the U.S. population.\nC_LIO_LIIgnoring the racial/ethnic diversity of the U.S. population is a missed scientific opportunity to fully understand the factors that lead to disease or health.\nC_LIO_LIU.S. biomedical research and study populations must better reflect the countrys changing demographics. Adequate representation of diverse populations in scientific research is imperative as a matter of social justice, economics, and science.\nC_LI

Genetics↗