Biology subjects

Lim, U.

Publications and source records attributed to Lim, U..

4 recordsLinked to original sources

bioRxiv2026

Gut Microbiota Mediates the Association between Diet Quality and Ectopic Adiposity: The Multiethnic Cohort Adiposity Phenotype Study

BackgroundHigher-quality diets have been associated with lower levels of ectopic fat deposited in the viscera and liver, which is hypothesized to be mediated in part by the gut microbiota. ObjectivesWe tested this hypothesis in a multi-ethnic imaging study using global (microbiome-wide) testing as well as a high-dimensional multiple-mediators regression framework to identify bacterial genera in the human gut that mediate the association between diet quality and ectopic adiposity. MethodsWe analyzed the cross-sectional data of 1,400 older adults (age 60-77) from five racial/ethnic groups in the Multiethnic Cohort Adiposity Phenotype Study (2013-2016). Overall diet quality was defined by adherence to the MIND diet. The relative abundance of 151 bacterial genera was quantified from 16S rRNA gene sequencing of the stool samples. Visceral fat, liver fat, and the presence of MASLD (metabolic dysfunction-associated steatotic liver disease) were determined based on magnetic resonance imaging (MRI). We used high-dimensional mediation analysis (HDMA) to estimate gut microbial mediation in the linear regression of visceral fat or liver fat, or in logistic regression of MASLD, on the MIND adherence score, adjusted for potential confounders. ResultsHigher diet quality was associated with lower ectopic adiposity: 12% less visceral fat area, 23% less liver fat, and a 49% less likelihood of having MASLD, comparing the highest to the lowest quartile of the MIND score. Using a distance-based global test, we confirmed overall significant microbial mediation of the inverse diet-ectopic fat association. From HDMA, four bacterial genera were identified as mediating the protective association with visceral fat, with the largest mediation conferred by Lachnospiraceae UCG.001 (12.2%). Two genera (Lachnoclostridium, Weissella) were shown to mediate the MIND association with both liver fat and MASLD. In particular, Lachnoclostridium mediated 13.6% of the liver fat association and 10.8% of the MASLD association, and Lachnospiraceae UCG.001 additionally mediated 12.1% of the liver fat association. ConclusionsOur results support the hypothesis that the gut microbiota contributes to conveying the effect of diet quality on preferred body fat distribution, e.g., involving bacteria that are known to produce short-chain fatty acids (Lachnospiraceae) or secondary bile acids (Lachnoclostridium).

microbiology↗

bioRxiv2021

Genome-wide Association Study of Pancreatic Fat: The Multiethnic Cohort Adiposity Phenotype Study

Several studies have found associations between higher pancreatic fat content and adverse health outcomes, such as diabetes and the metabolic syndrome, but investigations into the genetic contributions to pancreatic fat are limited. This genome-wide association study, comprised of 804 participants with MRI-assessed pancreatic fat measurements, was conducted in the ethnically diverse Multiethnic Cohort-Adiposity Phenotype Study (MEC-APS). Two genetic variants reaching genome-wide significance, rs73449607 on chromosome 13q21.2 (Beta = -0.67, P = 4.50x10-8) and rs7996760 on chromosome 6q14 (Beta = -0.90, P = 4.91x10-8) were associated with percent pancreatic fat on the log scale. Rs73449607 was most common in the African American population (13%) and rs79967607 was most common in the European American population (6%). Rs73449607 was also suggestively associated with lower risk of type 2 diabetes (OR = 0.95, 95% CI = 0.89-1.00, P = 0.047) in the Population Architecture Genomics and Epidemiology (PAGE) Study and the DIAbetes Genetics Replication and Meta-analysis (DIAGRAM), which included substantial numbers of non-European ancestry participants (53,102 cases and 193,679 controls). Rs73449607 is located in an intergenic region between GSX1 and PLUT, and rs79967607 is in intron 1 of EPM2A. PLUT, a linkRNA, regulates transcription of an adjacent gene, PDX1, that controls beta-cell function in the mature pancreas, and EPM2A encodes the protein laforin, which plays a critical role in regulating glycogen production. If validated, these variants may suggest a genetic component for pancreatic fat and a common etiologic link between pancreatic fat and type 2 diabetes.

cell biology↗

bioRxiv2019

Population specific reference panels are crucial for the genetic analyses of Native Hawai’ians: an example of the CREBRF locus

Statistical imputation applied to genome-wide array data is the most cost-effective approach to complete the catalog of genetic variation in a study population. However, imputed genotypes in underrepresented populations incur greater inaccuracies due to ascertainment bias and a lack of representation among reference individuals,, further contributing to the obstacles to study these populations. Here we examined the consequences due to the lack of representation by genotyping a functionally important, Polynesian-specific variant, rs373863828, in the CREBRF gene, in a large number of self-reported Native Hawaiians (N=3,693) from the Multiethnic Cohort. We found the derived allele of rs373863828 was significantly associated with several adiposity traits with large effects (e.g. 0.214 s.d., or approximately 1.28 kg/m2, per allele, in BMI as the most significant; P = 7.5x10-5). Due to the current absence of Polynesian representation in publicly accessible reference sequences, rs373863828 or any of its proxies could not be tested through imputation using these existing resources. Moreover, the association signals at this Polynesian-specific variant could not be captured by alternative approaches, such as admixture mapping. In contrast, highly accurate imputation can be achieved even if a small number (<200) of Polynesian reference individuals were available. By constructing an internal set of Polynesian reference individuals, we were able to increase sample size for analysis up to 3,936 individuals, and improved the statistical evidence of association (e.g. p = 1.5x10-7, 3x10-6, and 1.4x10-4 for BMI, hip circumference, and T2D, respectively). Taken together, our results suggest the alarming possibility that lack of representation in reference panels would inhibit discovery of functionally important, population-specific loci such as CREBRF. Yet, they could be easily detected and prioritized with improved representation of diverse populations in sequencing studies.

genetics↗

bioRxiv2017

Genetic Diversity Turns a New PAGE in Our Understanding of Complex Traits

Summary/AbstractGenome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development, and clinical guidelines. However, the dominance of European-ancestry populations in GWAS creates a biased view of the role of human variation in disease, and hinders the equitable translation of genetic associations into clinical and public health applications. The Population Architecture using Genomics and Epidemiology (PAGE) study conducted a GWAS of 26 clinical and behavioral phenotypes in 49,839 non-European individuals. Using strategies designed for analysis of multi-ethnic and admixed populations, we confirm 574 GWAS catalog variants across these traits, and find 38 secondary signals in known loci and 27 novel loci. Our data shows strong evidence of effect-size heterogeneity across ancestries for published GWAS associations, substantial benefits for fine-mapping using diverse cohorts, and insights into clinical implications. We strongly advocate for continued, large genome-wide efforts in diverse populations to reduce health disparities.

genetics↗