More Like this

1. Leveraging genomic diversity for discovery in an electronic health record linked biobank: the UCLA ATLAS Community Health Initiative

   https://doi.org/10.1186/s13073-022-01106-x  

   Johnson, Ruth ; Ding, Yi ; Venkateswaran, Vidhya ; Bhattacharya, Arjun ; Boulier, Kristin ; Chiu, Alec ; Knyazev, Sergey ; Schwarz, Tommer ; Freund, Malika ; Zhan, Lingyu ; et al ( December 2022 , Genome Medicine)

   Abstract Background Large medical centers in urban areas, like Los Angeles, care for a diverse patient population and offer the potential to study the interplay between genetic ancestry and social determinants of health. Here, we explore the implications of genetic ancestry within the University of California, Los Angeles (UCLA) ATLAS Community Health Initiative—an ancestrally diverse biobank of genomic data linked with de-identified electronic health records (EHRs) of UCLA Health patients ( N =36,736). Methods We quantify the extensive continental and subcontinental genetic diversity within the ATLAS data through principal component analysis, identity-by-descent, and genetic admixture. We assess the relationship between genetically inferred ancestry (GIA) and >1500 EHR-derived phenotypes (phecodes). Finally, we demonstrate the utility of genetic data linked with EHR to perform ancestry-specific and multi-ancestry genome and phenome-wide scans across a broad set of disease phenotypes. Results We identify 5 continental-scale GIA clusters including European American (EA), African American (AA), Hispanic Latino American (HL), South Asian American (SAA) and East Asian American (EAA) individuals and 7 subcontinental GIA clusters within the EAA GIA corresponding to Chinese American, Vietnamese American, and Japanese American individuals. Although we broadly find that self-identified race/ethnicity (SIRE) is highly correlated with GIA, we still observe marked differences between the two, emphasizing that the populations defined by these two criteria are not analogous. We find a total of 259 significant associations between continental GIA and phecodes even after accounting for individuals’ SIRE, demonstrating that for some phenotypes, GIA provides information not already captured by SIRE. GWAS identifies significant associations for liver disease in the 22q13.31 locus across the HL and EAA GIA groups (HL p -value=2.32×10 −16 , EAA p -value=6.73×10 −11 ). A subsequent PheWAS at the top SNP reveals significant associations with neurologic and neoplastic phenotypes specifically within the HL GIA group. Conclusions Overall, our results explore the interplay between SIRE and GIA within a disease context and underscore the utility of studying the genomes of diverse individuals through biobank-scale genotyping linked with EHR-based phenotyping. 

   more » « less
2. Exploring rain forest diversification using demographic model testing in the African foam‐nest treefrog Chiromantis rufescens

   https://doi.org/10.1111/jbi.13716  

   Leaché, Adam D. ; Portik, Daniel M. ; Rivera, Danielle ; Rödel, Mark‐Oliver ; Penner, Johannes ; Gvoždík, Václav ; Greenbaum, Eli ; Jongsma, Gregory F. M. ; Ofori‐Boateng, Caleb ; Burger, Marius ; et al ( October 2019 , Journal of Biogeography)

   Species with wide distributions spanning the African Guinean and Congolian rain forests are often composed of genetically distinct populations or cryptic species with geographic distributions that mirror the locations of the remaining forest habitats. We used phylogeographic inference and demographic model testing to evaluate diversification models in a widespread rain forest species, the African foam‐nest treefrogChiromantis rufescens.

   Guinean and Congolian rain forests, West and Central Africa.

   Chiromantis rufescens.

   We collected mitochondrial DNA (mtDNA) and single‐nucleotide polymorphism (SNP) data for 130 samples ofC. rufescens. After estimating population structure and inferring species trees using coalescent methods, we tested demographic models to evaluate alternative population divergence histories that varied with respect to gene flow, population size change and periods of isolation and secondary contact. Species distribution models were used to identify the regions of climatic stability that could have served as forest refugia since the last interglacial.

   Population structure withinC. rufescensresembles the major biogeographic regions of the Guinean and Congolian forests. Coalescent‐based phylogenetic analyses provide strong support for an early divergence between the western Upper Guinean forest and the remaining populations. Demographic inferences support diversification models with gene flow and population size changes even in cases where contemporary populations are currently allopatric, which provides support for forest refugia and barrier models. Species distribution models suggest that forest refugia were available for each of the populations throughout the Pleistocene.

   Considering historical demography is essential for understanding population diversification, especially in complex landscapes such as those found in the Guineo–Congolian forest. Population demographic inferences help connect the patterns of genetic variation to diversification model predictions. The diversification history ofC. rufescenswas shaped by a variety of processes, including vicariance from river barriers, forest fragmentation and adaptive evolution along environmental gradients.

    

   more » « less
3. Historical genomes elucidate European settlement and the African diaspora in Delaware

   https://doi.org/10.1016/j.cub.2023.04.069  

   Fleskes, Raquel E. ; Owsley, Douglas W. ; Bruwelheide, Karin S. ; Barca, Kathryn G. ; Griffith, Daniel R. ; Cabana, Graciela S. ; Schurr, Theodore G. ( June 2023 , Current Biology)

   The 17th-century colonization of North America brought thousands of Europeans to Indigenous lands in the Delaware region, which comprises the eastern boundary of the Chesapeake Bay in what is now the Mid- Atlantic region of the United States.1 The demographic features of these initial colonial migrations are not uni- formly characterized, with Europeans and European-Americans migrating to the Delaware area from other countries and neighboring colonies as single persons or in family units of free persons, indentured servants, or tenant farmers.2 European colonizers also instituted a system of racialized slavery through which they forcibly transported thousands of Africans to the Chesapeake region. Historical information about African- descended individuals in the Delaware region is limited, with a population estimate of less than 500 persons by 1700 CE.3,4 To shed light on the population histories of this period, we analyzed low-coverage genomes of 11 individuals from the Avery’s Rest archaeological site (circa 1675–1725 CE), located in Delaware. Previous osteological and mitochondrial DNA (mtDNA) sequence analyses showed a southern group of eight individ- uals of European maternal descent, buried 15–20 feet from a northern group of three individuals of African maternal descent.5 Autosomal results further illuminate genomic similarities to Northwestern European refer- ence populations or West and West-Central African reference populations, respectively. We also identify three generations of maternal kin of European ancestry and a paternal parent-offspring relationship between an adult and child of African ancestry. These findings expand our understanding of the origins and familial relationships in late 17th and early 18th century North America. 

   more » « less
4. Whole‐genome resequencing reveals persistence of forest‐associated mammals in Late Pleistocene refugia along North America’s North Pacific Coast

   https://doi.org/10.1111/jbi.14068  

   Colella, Jocelyn P. ; Lan, Tianying ; Talbot, Sandra L. ; Lindqvist, Charlotte ; Cook, Joseph A. ( March 2021 , Journal of Biogeography)

   Numerous glacial refugia have been hypothesized along North America's North Pacific Coast that may have increased divergence of refugial taxa, leading to elevated endemism and subsequently clustered hybrid zones following deglaciation. The locations and community composition of these ice‐free areas remains controversial, but whole‐genome sequences now enable detailed analysis of the demographic and evolutionary histories of refugial taxa. Here, we use genomic data to test spatial and temporal processes of diversification among martens with respect to the Coastal Refugium Hypothesis, to understand the role of climate cycling in shaping diversity across complex landscapes.

   North America and North Pacific Coast archipelagos.

   North American martens (Martes).

   Short‐read whole‐genome resequencing data were generated for 11 martens: fourM. americana, fourM. caurina, two hybrids, and one outgroup (Martes zibellina). Sampling was representative of known genetic clades within New World martens, including sampling within insular and continental hybrid zones and along the North Pacific Coast (five island populations).ADMIXTURE, F‐statistics, andD‐statistics (ABBA‐BABA) were used to identify introgression and infer directionality. Heterozygosity densities, estimated via PSMC, were used to characterize historical demography at and below the species level to infer refugial and colonization processes.

   Forest‐associated Pacific martens (M. caurina) are divided into distinct insular and continental clades consistent with the Coastal Refugium Hypothesis. There was no evidence of introgression on islands that received historical translocations of American pine martens (M. americana), but introgression was detected in two active zones of secondary contact: one insular and one continental. Only early‐generational hybrids were identified across multiple hybrid zones, a pattern consistent with potential genetic swamping ofM. caurinabyM. americana.

   Despite an incomplete fossil record, genomic evidence supports the persistence of forest‐associated martens, likely the insular Pacific marten lineage, along the western edges of the Alexander Archipelago during the Last Glacial Maximum. This discovery informs our understanding of refugial paleoenvironments, critical to interpreting refugial timing, duration, and community composition. Genomic reevaluations of other taxa along North America's North Pacific Coast may yield new and deeper perspectives on the history of refugial forest communities and the role of dynamic climate shifts in shaping high‐latitude diversity across complex insular landscapes.

    

   more » « less
5. Comparison of germline mutations in African American and Caucasian men with metastatic prostate cancer

   https://doi.org/10.1002/pros.24123  

   Ledet, Elisa M. ; Burgess, Earle F. ; Sokolova, Alexandra O. ; Jaeger, Ellen B. ; Hatton, Whitley ; Moses, Marcus ; Miller, Patrick ; Cotogno, Patrick ; Layton, Jodi ; Barata, Pedro ; et al ( April 2021 , The Prostate)

   The goal of this study is to evaluate germline genetic variants in African American men with metastatic prostate cancer as compared to those in Caucasian men with metastatic prostate cancer in an effort to understand the role of genetic factors in these populations.

   African American and Caucasian men with metastatic prostate cancer who had germline testing using multigene panels were used to generate comparisons. Germline genetic results, clinical parameters, and family histories between the two populations were analyzed.

   A total of 867 patients were included in this retrospective study, including 188 African American and 669 Caucasian patients. There was no significant difference in the likelihood of a pathogenic or likely‐pathogenic variants (PV/LPVs) between African American and Caucasian patients (p = .09). African American patients were more likely to have a variant of unknown significance than Caucasians (odds ratio [OR] = 1.95;p < .0001). BRCA1 PV/LPVs were higher in African Americans (OR = 4.86;p = .04). African American patients were less likely to have a PV/LPV in non‐BRCA DNA repair genes (OR = 0.30;p = .008). Family history of breast (OR = 2.09;p = .002) or ovarian cancer (OR = 2.33;p = .04) predicted PV/LPVs in Caucasians but not African‐Americans. This underscores the limitations of family history in AA men and the importance of personal history to guide germline testing in AA men.

   In metastatic prostate cancer patients, PV/LPVs of tested genes did not vary by race, BRCA1 PV/LPVs were more common in the African American subset. However, PV/LPVs in non‐BRCA DNA repair genes were less likely to be encountered in African Americans. Family history associated with genetic testing results in Caucasians only.

    

   more » « less