Multiethnic Cohort Study Research Articles

Adding ethnicity to cardiovascular risk prediction: external validation and model updating of SCORE2 using data from the multiethnic HELIUS population cohort

Abstract Background Current prediction models for mainland Europe do not include ethnicity, despite ethnic disparities in cardiovascular disease (CVD) risk. Purpose We evaluated the performance of SCORE2 across the largest ethnic groups in the Netherlands with and without the factor of ethnicity. Methods We linked data from 11,614 participants enrolled between 2011 and 2015 in the prospective, multi-ethnic HELIUS cohort study, the Netherlands, aged between 40 and 70 years without CVD with hospital data. Variables (age, sex, smoking status, blood pressure, cholesterol) and outcome first CVD event (myocardial infarction, stroke, CVD death) were consistent with SCORE2. We used Fine and Gray models to calculate sub-distribution hazard ratios (SHR) for South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan origin groups, relative to the Dutch origin group, on top of individual SCORE2 risk predictions. Model performance was evaluated by discrimination, calibration and net reclassification index (NRI). Results Overall, 274 fatal and non-fatal CVD events, and 146 non-cardiovascular deaths were observed during a median of 7.8 years follow-up (IQR 6.8–8.8). SHRs for CVD events were 1.86 (95% CI 1.31-2.65, p=0.0005) for the South-Asian Surinamese, 1.09 (95% CI 0.76-1.56) for the African-Surinamese, 1.48 (95% CI 0.94-2.31) for the Ghanaian, 1.63 (95% CI 1.09-2.44, p=0.018) for the Turkish, and 0.67 (95% CI 0.39-1.18) for the Moroccan origin groups. Adding ethnicity to SCORE2 led to comparable calibration and discrimination [0.76 (0.74-0.79) vs. 0.77 (95% CI 0.74-0.78)]. The NRI for adding ethnicity to SCORE2 was 0.24 (95% CI 0.18-0.31) for events and -0.12 (95% CI -0.13--0.12) for non-events. Conclusion Adding ethnic backgrounds improves risk classification of the SCORE2 risk prediction model in a middle-aged, multi-ethnic Dutch population, which may help to address disparities in CVDs through timely treatment.

Air Pollution and Breast Cancer Incidence in the Multiethnic Cohort Study.

Recent studies suggested fine particulate matter (PM2.5) exposure increases the risk of breast cancer, but evidence among racially and ethnically diverse populations remains sparse. Among 58,358 California female participants of the Multiethnic Cohort (MEC) Study followed for an average of 19.3 years (1993-2018), we used Cox proportional hazards regression to examine associations of time-varying PM with invasive breast cancer risk (n = 3,524 cases; 70% African American and Latino females), adjusting for sociodemographics and lifestyle factors. Subgroup analyses were conducted for race and ethnicity, hormone receptor status, and breast cancer risk factors. Satellite-based PM2.5 was associated with a statistically significant increased incidence of breast cancer (hazard ratio [HR] per 10 μg/m3, 1.28 [95% CI, 1.08 to 1.51]). We found no evidence of heterogeneity in associations by race and ethnicity and hormone receptor status. Family history of breast cancer showed evidence of heterogeneity in PM2.5-associations (Pheterogeneity = .046). In a meta-analysis of the MEC and 10 other prospective cohorts, breast cancer incidence increased in association with exposure to PM2.5 (HR per 10 μg/m3 increase, 1.05 [95% CI, 1.00 to 1.10]; P = .064). Findings from this large multiethnic cohort with long-term air pollutant exposure and published prospective cohort studies support PM2.5 as a risk factor for breast cancer. As about half of breast cancer cannot be explained by established breast cancer risk factors and incidence is continuing to increase, particularly in low- and middle-income countries, our results highlight that breast cancer prevention should include not only individual-level behavior-centered approaches but also population-wide policies and regulations to curb PM2.5 exposure.

Vitamin D Status in Late Pregnancy Was Related to Pregnancy Outcomes: A Multi-ethnic Cohort Study in Indonesia and Malaysia

Vitamin D Status in Late Pregnancy Was Related to Pregnancy Outcomes: A Multi-ethnic Cohort Study in Indonesia and Malaysia

Abstract A048: Association between ambient particulate matter and colorectal cancer incidence: The Multiethnic Cohort Study

Abstract Background: Growing evidence suggests that air pollution may be a risk factor for colorectal cancer (CRC). We examined the association between ambient particulate matter (PM) exposure and CRC risk within the Multiethnic Cohort Study (MEC), representing the first study to include a large sample of racial and ethnic minoritized populations. Methods: The MEC is a prospective study that recruited, from 1993 through 1996, men and women ages 45-75 years largely from five racial and ethnic groups (African American, Japanese American, Latino, Native Hawaiian, and Non-Hispanic White) living in Hawai‘i and California. This study included 98,675 California MEC participants, residing predominately in Los Angeles County. Satellite-based PM2.5 (PM with an aerodynamic diameter <2.5μm) exposures were estimated from a published spatiotemporal model. Kriging interpolation was used to estimate PM10 (PM <10μm) exposures using routine air monitoring data from the US Environmental Protection Agency. Time-varying PM exposures were assessed from time of recruitment through 12/31/2018. Incident invasive CRC cases were identified via linkage with the California Cancer Registry (n=3,217). Cox proportional hazards models were used to examine the association between PM and CRC risk using age as the time metric, with strata defined by age at cohort entry and race and ethnicity, and adjusting for demographic and lifestyle factors. Heterogeneity of the PM-CRC association was assessed by sex, race and ethnicity, and CRC subsite (right colon, left colon, rectum). Results: Risk of CRC increased with PM2.5 (per 10μg/m3 hazard ratio [HR] 1.13, 95% confidence interval [CI] 0.96-1.33) with a larger HR observed among females (HR 1.29, 95% CI 1.03-1.62) than males (HR 0.96, 95% CI 0.76-1.22) (Pheterogeneity=0.24). CRC risk was positively associated with PM2.5 across race and ethnicity (except for African American participants) with the largest HR observed among Latino participants (HR 1.47, 95% CI 1.03-2.08) (Pheterogeneity=0.20). There was no statistically significant heterogeneity of PM2.5 effect by tumor subsite (Pheterogeneity=0.07); although larger HRs were seen for left colon (HR 1.52, 95% CI 1.08- 2.14) and rectal cancers (HR 1.54, 95% CI 1.05-2.25) than right colon cancers (HR 1.09, 95% CI 0.88-1.35). PM10 was not associated with CRC risk (per 10 μg/m3; HR 1.02, 95% CI 0.93-1.22) with no evidence of heterogeneity in associations by sex or race and ethnicity (respective Pheterogeneity 0.75, 0.44). Although HRs for PM10 appeared to differ by CRC subsite (Pheterogeneity=0.03), the 95% CI of these HRs included the null (right HR 0.95, 95% CI 0.84-1.06; left HR 1.13, 95% CI 0.95-1.35; rectal HR 1.18, 95% CI 0.97-1.43). Conclusions: Preliminary findings suggest that PM2.5 exposure is associated with CRC risk with larger associations in females and, possibly, for left colon and rectal cancer. Additional studies are needed to confirm these findings and evaluate the potential biological pathways underlying these associations. Citation Format: Ugonna Ihenacho, Chiuchen Tseng, Jun Wu, Scott Fruin, Timothy V. Larson, Salma Shariff-Marco, Loïc Le Marchand, Daniel O. Stram, Lynne R. Wilkens, Christopher A. Haiman, Beate Ritz, Iona Cheng, Anna H. Wu. Association between ambient particulate matter and colorectal cancer incidence: The Multiethnic Cohort Study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A048.

Abstract A086: Racial and ethnic disparities in prostate cancer survival in the Multiethnic Cohort Study (MEC)

Abstract Background: Prostate cancer (PCa) survival has improved over the past 20 years due to advancements in treatment and screening. However, racial and ethnic disparities in PCa survival remain. Studying population differences in PCa survival may help identify underlying contributing factors. Methods: We conducted survival analyses among 10,651 African American, Latino, Native Hawaiian, Japanese American, and non-Hispanic White (NHW) men with an incident PCa diagnosis since 1993 who were part of the Multiethnic Cohort Study. Sub- hazard ratios (SHRs) and 95% confidence intervals (CI) were estimated using the Fine and Grey Subdistribution Hazards Model to account for competing risks in PCa-specific mortality, with age since diagnosis as the time metric. Multivariable models included age at PCa diagnosis, Gleason score, stage at diagnosis, and baseline values of education, initial treatment (radiation, surgery, hormone therapy, chemotherapy, or no active treatment), diabetes history, physical activity, BMI, smoking status, and dietary intakes linked to PCa progression (tomatoes, whole milk, fatty fish, processed meat, saturated fat, and alcohol). We also performed stratified analyses by tumor stage (localized or regional/distant) and Gleason score (≤7 or >7). Associations were considered statistically significant at P < 0.05. Results: Of 10,651 men diagnosed with PCa over 27 years of follow-up (mean duration, 8.4 years), 1,324 (12.4%) died of PCa. Those with lower Gleason scores were less likely to die than those with higher scores (6.8% of men with Gleason score ≤7 vs 21.3% of men with Gleason score >7, p<0.001). Likewise, men with localized disease were less likely to die than men with regional/distant disease (7.5% of men with localized disease vs. 29.2% of men with regional/distant disease, p<0.001). Japanese Americans had significantly lower mortality compared with NHWs (SHR=0.63, 95% CI:0.51, 0.79, p<0.001), consistently observed across stage and Gleason score: localized (SHR=0.64, 95% CI: 0.48, 0.87, p<0.001); regional/distant (SHR=0.63, 95% CI: 0.45, 0.88, p=0.01); Gleason ≤7 (SHR=0.61, 95% CI: 0.44, 0.86, p<0.001); and Gleason score >7 (SHR=0.59, 95% CI: 0.43, 0.79, p<0.001). PCa-specific mortality was significantly higher among African Americans compared to NHWs (SHR=1.31, 95% CI: 1.08-1.60, p=0.01). This difference was more pronounced for less aggressive tumors: localized (SHR=1.50, 95% CI: 1.15, 1.96, p<0.001); Gleason ≤7 (SHR=1.28, 95% CI: 0.95, 1.71, p=0.11). Lastly, we did not observe significant differences in PCa mortality for Latinos and Native Hawaiians compared to NHWs overall or by disease severity. Conclusions: Japanese American have ∼40% lower and African Americans have ∼30% higher PCa-specific mortality relative to NHWs, even after accounting for lifestyle/behavioral factors, stage, Gleason score, and treatment. Further investigations are needed to explore social and cultural factors that impact care as well as tumor-based characteristics that may vary between populations to understand these disparities in PCa mortality. Citation Format: Wei Xiong, Fei Chen, Ann S. Hamilton, David Conti, Raymond Hughley, David Bogumil, Anqi Wang, Song-Yi Park, Peggy Wan, Lynne R. Wilkens, Loïc Le Marchand, Brenda Y. Hernandez, Christopher A. Haiman. Racial and ethnic disparities in prostate cancer survival in the Multiethnic Cohort Study (MEC) [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A086.

Abstract C146: Racial and Ethnic Differences in the Biological Signatures of Breast Tumors and the Immune-microenvironment: The Multiethnic Cohort Study

Abstract This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR008) of the Conference Program/Proceedings. Citation Format: Lenora WM Loo, Yuquing Li, Kami K. White, Jose A. Aparicio, Veronica W. Setiawan, Christopher A. Haiman, Anna H. Wu, Lynne R. Wilkens, Loic Le Marchand, Brenda Y Hernandez, Iona Cheng. Racial and Ethnic Differences in the Biological Signatures of Breast Tumors and the Immune-microenvironment: The Multiethnic Cohort Study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C146.

Abstract B152: Joint Associations of Neighborhood Socioeconomic Status and Education on the Incidence of Colorectal Cancer: The Multiethnic Cohort Study

Abstract Background: Colorectal cancer (CRC) is the 3rd most diagnosed cancer worldwide. When considered separately, both neighborhood- and individual-level SES exposures have been associated with CRC incidence. However, the joint associations of neighborhood- and individual-level SES on CRC incidence have not been examined. Methods: In a prospective study of 153,725 Multiethnic Cohort (MEC) participants (24,764 African American, 44,447 Japanese American, 34,974 Latino, 11,511 Native Hawaiian, and 38,029 White participants) recruited from predominantly Los Angeles County, California (CA), and Hawaii (HI), we examined the joint association of neighborhood SES (nSES) and individual-level education with CRC incidence (CA: 2,519, HI: 2,210 cases). Education, other demographics, and health behaviors were self-reported in the baseline questionnaire (1993-1996). CRC diagnosis was determined via linkages with state cancer registries. nSES was derived using a composite score based on 1990 US Census block group data and assigned to geocoded baseline addresses. Our joint SES measure included four categories: high nSES (quintiles 4-5) and high education (> high school), high nSES and low education (≤ high school), low nSES (quintiles 1-3) and high education, and low nSES and low education. State-specific hazards ratios (HR) for CRC incidence were estimated for joint SES categories. Cox regression adjusted for age at cohort entry, CRC family history, polyp history, obesity, diabetes, diet, alcohol, smoking, physical activity, and NSAID, multivitamin, and hormone therapy use. Subgroup analyses were conducted by sex, race, and ethnicity. Results: For HI MEC participants, compared to individuals with high nSES and high education, risk for CRC was highest among those with low nSES and low education (HR=1.27; 95% CI:1.11-1.45) followed by high nSES and low education (HR=1.25; 95% CI:1.12-1.41), and low nSES and high education (HR=1.17; 95% CI: 1.03-1.31). This pattern of association was observed across sex but differed across race and ethnicity (p-heterogeneity=0.04). The overall pattern of association was observed among White participants in HI. However, for Japanese American individuals in HI, compared to those with high nSES and high education, risk for CRC was highest for low nSES and high education (HR=1.29; 95% CI:1.09-1.53) and high nSES and low education (HR= 1.28; 95% CI; 1.10-1.50). For Native Hawaiian individuals, compared to those with high nSES and high education, CRC risk was highest for those with low nSES and low education (HR=1.70; 95% CI: 1.20-2.42). Associations were not statistically significant between the joint SES measure and CRC risk in CA (HRs: 0.92-0.97). Conclusion: Among MEC participants in HI, CRC risk varied with the joint measure of nSES and education across racial and ethnic groups. These findings emphasize the importance of considering the joint associations of neighborhood- and individual-level SES in understanding racial and ethnic disparities in CRC. Citation Format: Catherine Walsh, Meera Sangaramoorthy, Songyi Park, Sung-shim (Lani) Park, Gertraud Maskarinec, Lynne Wilkens, Christopher Haiman, Anna Wu, Salma Shariff-Marco, Loic Le Marchand, Iona Cheng. Joint Associations of Neighborhood Socioeconomic Status and Education on the Incidence of Colorectal Cancer: The Multiethnic Cohort Study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B152.

Dietary pattern trajectories in early childhood and their associations with patterns of maternal feeding practices in a multi-ethnic Asian cohort

BackgroundMaternal feeding practices play a major role in children’s dietary intakes. However, there is limited data on the associations between trajectories of dietary patterns (DPs) and patterns of maternal feeding practices during early childhood.MethodsUsing data from a multi-ethnic Asian cohort study, namely the Growing Up in Singapore Towards healthy Outcomes (GUSTO), dietary intakes were measured using Food Frequency Questionnaires in children at 18 months, 5 and 7 years of age. Maternal feeding practices were assessed using validated questionnaires at 15 months, 3 and 5 years of age. Principal component analysis was used to derive 2 major DPs at all time-points as well as patterns of maternal feeding practices. Group-based trajectory modelling was used to identify trajectory groups for the derived DPs. Multivariable logistic regression examined associations between patterns of maternal feeding practices and DP trajectory groups.ResultsTwo DPs, namely the ‘healthy’ and ‘less healthy’ were consistently derived at 18 months, 5 and 7 years of age. From each DP, 2 stable DP trajectory groups were further identified between 18 months and 7 years of age. For the ‘healthy’ DP trajectory, majority of the children (Group 1) formed a consistent average adherence trajectory group (91.8%) while the remaining children (Group 2) showed a higher but decreasing adherence (8.2%) to this DP. For the ‘less healthy’ DP trajectory, most children (Group 1) formed a consistent average adherence trajectory (95.5%), while the remainder (Group 2) showed consistent higher adherence to this ‘less healthy’ DP (4.5%). Two patterns of maternal feeding practices were derived and labelled as ‘structured with autonomy support’ and ‘coercive control’, respectively, at ages 15 months, 3 and 5 years. Children whose mothers showed high adherence to the structured with autonomy support feeding practices at age 5 years were significantly more likely to be associated with the higher but decreasing ‘healthy’ DP trajectory group [OR = 3.62 (95% CI: 1.64, 7.99)].ConclusionsA small number of children in this multi-ethnic study showed high adherence to the ‘healthy’ or ‘less healthy’ DP trajectory groups, respectively, while the majority showed average adherence to either of these trajectories. The positive association between structured with autonomy support maternal feeding practices and higher z-scores for the healthy DP trajectory highlights the importance of guiding parents on appropriate feeding practices.

The Importance of Racially and Ethnically Inclusive Gait Speed Reference Values in Individuals 90 Years and Older: LifeAfter90.

Clinicians use reference values to contextualize physical performance scores, but data are sparse in individuals 90years and older and racial/ethnic diversity is limited in existing studies. Gait speed provides valuable information about an individual's health status. Slow gait speed is associated with falls, cognitive decline, and mortality. Here, we report gait speed reference values in a racially/ethnically diverse oldest-old cohort. LifeAfter90 is a multiethnic cohort study of individuals 90years and older. Participants are long-term members of an integrated healthcare delivery system without a dementia diagnosis at enrollment. We assessed gait speed using the 4-m walk test and calculated means, standard deviations, and percentiles by age, sex, assistive device use, and device type. We used linear regression to compare means by sex, age, device use and type, living situation and arrangement, and race/ethnicity. The mean age of the 502 participants was 92.9 (range 90.1-102.8) years. Of these, 62.6% were women, 34.7% were college educated, 90.8% lived in a private residence, 20.9% self-reported as Asian, 22.5% as Black, 11.8% as Hispanic, 35.7% as White, and 9.2% as multiple, "other," or declined to state. The overall mean gait speed was 0.54 m/s (women=0.51 m/s, men=0.58 m/s). Mean gait speeds were 0.58 m/s, 0.53 m/s, and 0.48 m/s in the 90 to 91, 92 to 93, and 94+ age categories, respectively. In those without a device, mean gait speed was 0.63 m/s compared to 0.40 m/s in those with a device (cane=0.44 m/s, walker=0.37 m/s). Mean gait speed was significantly slower in women compared to men, age category 94+ compared to 90 to 91, participants with a device compared to those without, participants with a walker compared to a cane, and Black participants compared to Asian and White participants. However, differences by race/ethnicity were attenuated when chronic health conditions were considered. Reference values developed from this multiethnic 90+ cohort will help clinicians interpret gait speed measures and tailor recommendations toward a 90+ population that is growing in number and in racial/ethnic diversity.

Different types and numbers metabolic abnormalities and risk of gallbladder stone disease in adults.

Metabolic abnormalities in the body increase the risk of gallbladder stones and their complications, which brings a great economic and social burden. The relationship between different types and amounts of metabolic abnormalities and gallstone risk in different sexes is poorly documented and controversial. Based on the baseline survey data of the Chinese Multi-Ethnic Cohort (CMEC) study, 4,075 Chinese adults aged 30-79 years with complete abdominal ultrasound results and metabolic index data. Logistic regression model was used to evaluate the correlation between five metabolic abnormalities and gallstones, and to explore the gender difference. The detection rate of gallbladder stones was found to be 7.0%, with a higher rate in women (8.6%) than in men (4.1%). Logistic results showed adjustment odds ratio (ORs) and 95% confidence interval (95% CI) of dysglycemia + hypertension + central obesity in 3 metabolic combinations was 4.459 (1.653, 12.029). The four metabolic combinations, dysglycemia + dyslipidemia + hypertension + central obesity, dysglycemia + dyslipidemia + hypertension + abnormal blood uric acid and dysglycemia + dyslipidemia + central obesity + abnormal blood uric acid adjusted OR and 95%CI were 3.342 (1.459, 7.659), 5.439 (1.555, 19.018) and 2.971 (1.187, 7.435), respectively. Gender-stratified analysis found that "any three or more metabolic abnormalities and their components were associated with gallstone risk, more significantly in women. Different types and amounts of five metabolic abnormalities were associated with the risk of gallstone development, and the differences were more significant in women than men.

Reproductive Factors and Thyroid Cancer Risk: The Multiethnic Cohort Study.

Background: Women are three times more likely to be diagnosed with thyroid cancer than men, with incidence rates per 100,000 in the United States of 20.2 for women and 7.4 for men. Several reproductive and hormonal factors have been proposed as possible contributors to thyroid cancer risk, including age at menarche, parity, age at menopause, oral contraceptive use, surgical menopause, and menopausal hormone therapy. Our study aimed to investigate potential reproductive/hormonal factors in a multiethnic population. Methods: Risk factors for thyroid cancer were evaluated among female participants (n = 118,344) of the Multiethnic Cohort Study. The cohort was linked to Surveillance, Epidemiology, and End Results cancer incidence and statewide death certificate files in Hawaii and California, with 373 incident papillary thyroid cancer cases identified. Exposures investigated include age at menarche, parity, first pregnancy outcome, birth control use, and menopausal status and type. Multivariable Cox proportional hazards models were used to obtain relative risk (RR) of papillary thyroid cancer and their 95% confidence intervals (CI). Covariates included age, race and ethnicity, reproductive history, body size, smoking, and alcohol consumption. Results: We observed a statistically significant increased risk of papillary thyroid cancer for oophorectomy (adjusted RR 1.58, 95% CI: 1.26, 1.99), hysterectomy (adjusted RR 1.65, 95% CI: 1.33, 2.04), and surgical menopause (adjusted RR 1.55, 95% CI: 1.22, 1.97), and decreased risk for first live birth at ≤20 years of age versus nulliparity (adjusted RR 0.66, 95% CI: 0.46, 0.93). These associations did not vary by race and ethnicity (p het > 0.44). Conclusion: The reproductive risk factors for papillary thyroid cancer reported in the literature were largely confirmed in all racial and ethnic groups in our multiethnic population, which validates uniform obstetric and gynecological practice.

Genomic structural variations link multiple genes to bone mineral density in a multi-ethnic cohort study: Louisiana osteoporosis study.

Osteoporosis, characterized by low BMD, is a highly heritable metabolic bone disorder. Although single nucleotide variations (SNVs) have been extensively studied, they explain only a fraction of BMD heritability. Although genomic structural variations (SVs) are large-scale genomic alterations that contribute to genetic diversity in shaping phenotypic variations, the role of SVs in osteoporosis susceptibility remains poorly understood. This study aims to identify and prioritize genes that harbor BMD-related SVs. We performed whole genome sequencing on 4982 subjects from the Louisiana Osteoporosis Study. To obtain high-confidence SVs, the detection of SVs was performed using an ensemble approach. The SVs were tested for association with BMD variation at the hip (HIP), femoral neck (FNK), and lumbar spine (SPN), respectively. Additionally, we conducted co-occurrence analysis using multi-omics approaches to prioritize the identified genes based on their functional importance. Stratification was employed to explore the sex- and ethnicity-specific effects. We identified significant SV-BMD associations: 125 for FNK-BMD, 99 for SPN-BMD, and 83 for HIP-BMD. We observed SVs that were commonly associated with both FNK and HIP BMDs in our combined and stratified analyses. These SVs explain 13.3% to 19.1% of BMD variation. Novel bone-related genes emerged, including LINC02370, ZNF family genes, and ZDHHC family genes. Additionally, FMN2, carrying BMD-related deletions, showed associations with FNK or HIP BMDs, with sex-specific effects. The co-occurrence analysis prioritized an RNA gene LINC00494 and ZNF family genes positively associated with BMDs at different skeletal sites. Two potential causal genes, IBSP and SPP1, for osteoporosis were also identified. Our study uncovers new insights into genetic factors influencing BMD through SV analysis. We highlight BMD-related SVs, revealing a mix of shared and specific genetic influences across skeletal sites and gender or ethnicity. These findings suggest potential roles in osteoporosis pathophysiology, opening avenues for further research and therapeutic targets.

Epigenome-wide association study of ambient air pollution in a racially and ethnically diverse population of smokers: The Multiethnic Cohort Study

Epigenome-wide association study of ambient air pollution in a racially and ethnically diverse population of smokers: The Multiethnic Cohort Study

Plasma mineral concentrations and fetal growth trajectories: a prospective multi-ethnic Asian cohort study

Plasma mineral concentrations and fetal growth trajectories: a prospective multi-ethnic Asian cohort study

Association between obesity phenotypes and dietary patterns: A two-step cluster analysis based on the China multi-ethnic cohort study

ObjectiveThis study aimed to explore obesity phenotypes and investigate their association with dietary patterns. MethodsData were obtained from the baseline survey conducted in the China Multi-Ethnic Cohort Study from July 2018 to August 2019. All participants with a body mass index of at least 24 kg/m2 were enrolled and underwent a questionnaire survey, physical examination, and clinical laboratory tests. A two-step cluster analysis was employed to classify the participants into phenotypes. Dietary information was collected using the food frequency questionnaire, and principal component analysis was conducted to identify distinct dietary patterns. ResultsWe analyzed the data of 8757 participants. They were categorized based on demographic characteristics, biochemical indicators, and anthropometric measurements into two distinct clusters identified as metabolically healthy obesity and metabolically unhealthy obesity (MUO). Key predictors included serum uric acid, sex, and diastolic blood pressure. Subgroup analysis by sex identified three distinct clusters within both male and female participants. The MUO group had the highest prevalence of a range of chronic noncommunicable diseases. The analysis uncovered three unique dietary patterns among participants classified as the premium protein, rice-oil-red meat, and oil-salt patterns. Notably, the MUO subgroup demonstrated significantly higher factor scores for both the rice-oil-red meat and oil-salt patterns. ConclusionsObesity phenotypes are closely related to metabolic and demographic characteristics, with serum uric acid being a significant factor in categorizing the metabolic states of obesity. The rice-oil-red meat and oil-salt patterns may be related to the metabolic status of individuals with obesity.

Breast, Colorectal, and Prostate Cancer Incidence among Filipino Americans by Generational Status in the Multiethnic Cohort Study.

Filipino Americans constitute 12% and 4% of the respective populations of Hawaii and California, with a large proportion of immigrants experiencing increasing cancer rates. This study investigated the incidence of colorectal, breast, and prostate cancers by generational status in the Multiethnic Cohort. We analyzed 10,495 Filipino Multiethnic Cohort first-, second-, and third-generation participants, in which 26.8% were of mixed race and ethnicity. Linkage to statewide cancer registries identified 375 breast, 249 colorectal, and 436 prostate cancer incident cases. Cox models were used to calculate HRs and 95% confidence intervals (CI) for the association between generational status and cancer incidence. Models were adjusted for age at cohort entry and cancer-specific covariates that were chosen based on stepwise regression. Compared with the first generation, colorectal cancer showed a significantly higher incidence in the second and third generations with respective HRs of 1.43 (95% CI, 1.04, 1.98) and 1.76 (95% CI, 1.29, 2.38). This association was attenuated after adjustment for relevant covariates. Breast cancer incidence was elevated in the third versus first generation (HR = 1.29; 95% CI, 1.01, 1.63) even in the fully adjusted model, whereas little difference was observed for prostate cancer. In this prospective study, we found differences in incidence by generational status, specifically colorectal cancer among men and female breast cancer. Understanding behavioral changes due to acculturation is warranted to mitigate cancer risks in migrant populations.

Association Between the Copper-to-Zinc Ratio and Cardiovascular Disease Among Chinese Adults: A China Multi-ethnic Cohort (CMEC) Study.

The impact of metal exposure on cardiovascular diseases has become an increasingly concerning topic. To date, few studies have investigated the relationship between the copper-to-zinc ratio and CVD (Cardiovascular disease). This China multi-ethnic cohort study explored the association between the copper-to-zinc ratio and CVD in Chinese adults. The study included a sample size of 9878 people. Logistic regression analysis was used to examine the correlation between urinary copper, urinary zinc, and the copper-to-zinc ratio and CVD prevalence. Restricted cubic spline (RCS) analysis was used to investigate the potential dose-response relationships among copper-to-zinc ratio, urinary copper, urinary zinc, and CVD prevalence. In addition, the least absolute shrinkage and selection operator (LASSO) regression method was used to identify significant risk factors associated with CVD, leading to the development of a nomogram. The predictive performance of the nomogram model for CVD was assessed using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Compared with the copper-to-zinc ratio in Q1, the copper-to-zinc ratio in Q4 was associated with CVD after adjusting for all potential confounders (Model 3) (Q4, odds ratio [OR] 0.608, 95% confidence interval [CI] 0.416-0.889, P = 0.010). After adjusting for all potential confounders (Model 3), urinary copper levels in Q4 were associated with CVD (Q4, odds ratio [OR] 0.627, 95% confidence interval [CI] 0.436-0.902, P = 0.012). No significant difference was found between urinary zinc levels and CVD. The RCS showed a linear dose-response relationship between the copper-to-zinc ratio and CVD (P for overall = 0.01). The nomogram based on the influencing factors examined with LASSO showed good predictive power, and the AUC was 76.3% (95% CI 73.7-78.9%). Our results suggest that there is a significant linear negative correlation between the copper-to-zinc ratio and CVD in Chinese adults and that it has good predictive value for CVD.

Association of Adiposity Phenotypes with 27-Hydroxycholesterol and Sex Hormones: The Multiethnic Cohort Study.

The distribution of body fat has been linked to circulating levels of lipids and sex-steroid hormones. The cholesterol metabolite and endogenous selective estrogen receptor modulator, 27-hydroxychlolesterol (27HC), may be influenced by adiposity phenotypes, particularly among females. No study has examined the relationships of 27HC and steroid hormones with adiposity phenotypes. To investigate the associations of 27HC and steroid hormones with detailed adiposity phenotypes among a multiethnic population of postmenopausal females. A cross-sectional study was conducted among 912 postmenopausal females from the Multiethnic Cohort- Adiposity Phenotype study. Multivariable linear regression examined the associations of circulating levels of 27HC, steroid hormones, and sex hormone-binding globulin (SHBG) with detailed adiposity phenotypes, adjusting for demographics, lifestyle factors, diabetes status, and use of lipid lowering drugs. Subgroup analyses were conducted across race and ethnicity. Total fat mass (P-trend=0.003), subcutaneous adipose tissue (SAT) (P-trend=0.006), and superficial subcutaneous adipose tissue (sSAT) (P-trend=4.41x10-4) were inversely associated with circulating 27HC levels. In contrast, visceral adipose tissue (VAT) (P-trend=0.003) and liver fat (P-trend=0.005) were positively associated with 27HC levels. All adiposity phenotypes were associated with higher levels of free estradiol, testosterone and lower levels of SHBG. Generally, similar patterns of associations were observed across race and ethnicity. Adiposity phenotypes, such as SAT, VAT, and liver fat, were differentially associated with circulating 27HC, while consistent directions of associations were seen for circulating hormones among postmenopausal females. Future studies are warranted to further understand the biology and relationships of 27HC and adiposity-related diseases.

Socioeconomic Status, Lifestyle, and DNA Methylation Age Among Racially and Ethnically Diverse Adults

Variation in DNA methylation at specific loci estimates biological age, which is associated with morbidity, mortality, and social experiences. Aging estimates known as epigenetic clocks, including the Dunedin Pace of Aging Calculated From the Epigenome (DunedinPACE), were trained on data predominately from individuals of European ancestry; however, limited research has explored DunedinPACE in underrepresented populations experiencing health disparities. To investigate associations of neighborhood and individual sociobehavioral factors with biological aging in a racially and ethnically diverse population. This cohort study, part of the Multiethnic Cohort study conducted from May 1993 to September 1996 to examine racial and ethnic disparities in chronic diseases, integrated biospecimen and self-reported data collected between April 2004 and November 2005 from healthy Hawaii residents aged 45 to 76 years. These participants self-identified as of Japanese American, Native Hawaiian, or White racial and ethnic background. Data were analyzed from January 2022 to May 2024. DNA methylation data were generated from monocytes enriched from cryopreserved lymphocytes and used to derive DunedinPACE scores from November 2017 to June 2021. Neighborhood social economic status (NSES) was estimated from 1990 US Census Bureau data to include factors such as educational level, occupation, and income. Individual-level factors analyzed included educational level, body mass index (BMI), physical activity (PA), and diet quality measured by the Healthy Eating Index (HEI). Linear regression analysis of DunedinPACE scores was used to examine their associations with NSES and sociobehavioral variables. A total of 376 participants were included (113 [30.1%] Japanese American, 144 [38.3%] Native Hawaiian, and 119 [31.6%] White; 189 [50.3%] were female). Mean (SE) age was 57.81 (0.38) years. Overall, mean (SE) DunedinPACE scores were significantly higher among females than among males (1.28 [0.01] vs 1.25 [0.01]; P = .005); correlated negatively with NSES (R = -0.09; P = .08), HEI (R = -0.11; P = .03), and educational attainment (R = -0.15; P = .003) and positively with BMI (R = 0.31; P < .001); and varied by race and ethnicity. Native Hawaiian participants exhibited a higher mean (SE) DunedinPACE score (1.31 [0.01]) compared with Japanese American (1.25 [0.01]; P < .001) or White (1.22 [0.01]; P < .001) participants. Controlling for age, sex, HEI, BMI, and NSES, linear regression analyses revealed a negative association between educational level and DunedinPACE score among Japanese American (β, -0.005 [95% CI, -0.013 to 0.002]; P = .03) and Native Hawaiian (β, -0.003 [95% CI, -0.011 to 0.005]; P = .08) participants, yet this association was positive among White participants (β, 0.007; 95% CI, -0.001 to 0.015; P = .09). Moderate to vigorous PA was associated with lower DunedinPACE scores only among Native Hawaiian participants (β, -0.006; 95% CI, -0.011 to -0.001; P = .005), independent of NSES. In this study of a racially and ethnically diverse sample of 376 adults, low NSES was associated with a higher rate of biological aging measured by DunedinPACE score, yet individual-level factors such as educational level and physical activity affected this association, which varied by race and ethnicity. These findings support sociobehavioral interventions in addressing health inequities.

Temporal relationship between hepatic steatosis and fasting blood glucose elevation: a longitudinal analysis from China and UK

BackgroundThe link between nonalcoholic fatty liver disease and type 2 diabetes has not been fully established. We investigated the temporal relationship between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), quantitatively assessed the impact, and evaluated the related mediation effect.MethodsThis study involved participants from the China Multi-Ethnic Cohort Study and the UK Biobank. We performed cross-lagged path analysis to compare the relative magnitude of the effects between NAFLD and T2D using two-period biochemical data. Hepatic steatosis and fasting blood glucose elevation (FBG) represented NAFLD and T2D respectively. We fitted two separate Cox proportional-hazards models to evaluate the influence of hepatic steatosis on T2D. Furthermore, we applied the difference method to assess mediation effects.ResultsIn cross-lagged path analyses, the path coefficients from baseline hepatic steatosis to first repeat FBG (βCMEC = 0.068, βUK−Biobank = 0.033) were significantly greater than the path coefficients from baseline FBG to first repeat hepatic steatosis (βCMEC = 0.027, βUK−Biobank = -0.01). Individuals with hepatic steatosis have a risk of T2D that is roughly three times higher than those without the condition (HR = 3.478 [3.314, 3.650]). Hepatic steatosis mediated approximately 69.514% of the total effect between obesity and follow-up T2D.ConclusionsOur findings contribute to determining the sequential relationship between NAFLD and T2D in the causal pathway, highlighting that the dominant pathway in the relationship between these two early stages of diseases was the one from hepatic steatosis to fasting blood glucose elevation. Individuals having NAFLD face a significantly increased risk of T2D and require long-term monitoring of their glucose status as well.