Exploring depression treatment response by using polygenic risk scoring across diverse populations.

Treatment-resistant depression (TRD), usually defined as limited or no response to at least two antidepressants, occurs in approximately one-third of individuals diagnosed with major depressive disorder (MDD). Studies of individuals of European ancestry highlight a genetic overlap between TRD and MDD. We analyzed two large and diverse biobanks, the UCLA ATLAS Community Health Study (ATLAS) and the All of Us Research Program (AoU), to test for associations between a polygenic score for major depression (MDD-PGS) and TRD.

Generalizability of PGS for breast cancer risk in a Los Angeles biobank.

Polygenic scores (PGSs) summarize the combined effect of common risk variants and are associated with breast cancer risk in patients without identifiable monogenic risk factors. One of the most well-validated PGSs in breast cancer to date is PGS, which was developed from a Northern European biobank but has shown attenuated performance in non-European ancestries. We further investigate the generalizability of the PGS for American women of European (EA), African (AFR), Asian (EAA), and Latinx (HL) ancestry within one institution with a singular electronic health record (EHR) system, genotyping platform, and quality control process.

Polygenic scores for tobacco use provide insights into systemic health risks in a diverse EHR-linked biobank in Los Angeles.

Tobacco use is a major risk factor for many diseases and is heavily influenced by environmental factors with significant underlying genetic contributions. Here, we evaluated the predictive performance, risk stratification, and potential systemic health effects of tobacco use disorder (TUD) predisposing germline variants using a European- ancestry-derived polygenic score (PGS) in 24,202 participants from the multi-ancestry, hospital-based UCLA ATLAS biobank. Among genetically inferred ancestry groups (GIAs), TUD-PGS was significantly associated with TUD in European American (EA) (OR: 1.

Interplay Of Serum Bilirubin and Tobacco Smoking with Lung and Head and Neck Cancers in a Diverse, EHR-linked Los Angeles Biobank.

Background: Bilirubin is a potent antioxidant with a protective role in many diseases. We examined the relationships between serum bilirubin (SB) levels, tobacco smoking (a known cause of low SB), and aerodigestive cancers, grouped as lung cancers (LC) and head and neck cancers (HNC).

Methods: We examined the associations between SB, LC, and HNC using data from 393,210 participants from a real-world, diverse, de-identified data repository and biobank linked to the UCLA Health system.

Interplay Of Serum Bilirubin and Tobacco Smoking with Lung and Head and Neck Cancers in a Diverse, EHR-linked Los Angeles Biobank.

Background: Bilirubin is a potent antioxidant with a protective role in many diseases. We examined the relationships between serum bilirubin (SB) levels, tobacco smoking (a known cause of low SB), and aerodigestive cancers, grouped as lung (LC) and head and neck (HNC).

Methods: We examined the associations between SB, LC and HNC using data from 393,210 participants from UCLA Health, employing regression models, propensity score matching, and polygenic scores.

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

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.