Family history of dementia and brain health in childhood and middle age: a prospective community-based study.

We aimed to determine the association of family history of dementia with structural brain measures and cognitive performance in childhood and mid-life adulthood. We studied 1,259 parents (mean age: 47.3 years, range 31.9-67.4) and 866 of their children (mean age [range] at brain MRI: 9.9 years [8.8-11.9], and for cognition: 13.5 years [12.6-15.8]) of the population-based Generation R Study. Parents filled in a questionnaire on family history, and both parents and children underwent cognitive assessment and neuroimaging. Of all participants, 109 parents (8.6%) reported a parental family history of dementia and 73 children (8.4%) had a grandparental history of dementia with mean age of dementia diagnosis in those affected 75 years (± 7.3). We observed no associations of dementia family history with cognitive ability in either parents or their children, except for worse Purdue pegboard in parents with a parental history of dementia, compared to those without (mean difference [95%CI]: -1.23 [-2.15; -0.31], test range: 21-52). In parents and children, neuroimaging measures did not differ significantly by family history. Results did not depend on age, sex, and APOE genotype. Family history of dementia was associated with worse manual dexterity in mid-life adulthood, but not with any other measures of cognitive ability or subclinical brain health in childhood and mid-life. These findings suggest that the association of family history with dementia risk is due chiefly to neurodegenerative rather than neurodevelopmental processes, and might first present with reduced motor skills.

Early cancer screening surveillance in one medical center of China.

Objectives: Cancer screening aims to detect and treat malignant lesions at an early stage and to prolong patients' lifetime. There is still a lack of effective cancer screening programs in China. We initiated a screening project in 2018 and this study presented the cancer screening status in China. Methods: We conducted a cross-sectional study in one cancer-care medical center of China. The screening program included routine blood tests, plasma tumor markers, gastric endoscopy, colonoscopy, ultrasound, and computed tomography (CT) scans. Screening results were presented as sensitivity, specificity and positive predictive values (PPVs). Results: Twenty-three (1.46%) out of 1,576 participants were eventually diagnosed with malignant tumors or high-grade intraepithelial neoplasia (HGIN). A family history of malignancy (78.26% in diagnosed cancer and HGIN vs. 46.36% in the others) was the only statistically significant parameter associated with cancer detection (p = 0.002). None of the common tumor markers were associated with the cancers screened. Except for colonoscopy (50.00%) and ultrasound for renal cancer (66.67%), the sensitivities of most screening methods were 100%. The specificities of all the screening means were above 96%. Most PPVs ranged from 30-60%. Conclusion: We emphasized risk stratification for early cancer screening, such as a family history of cancer. The survey illustrated that gastric endoscopy, colonoscopy, ultrasound, and lung CT for early cancer screening had high specificity, reasonable sensitivity, and PPV. We anticipated this report would motivate larger-sample studies to estimate the risk-to-benefit ratio of cancer screening and urge the establishment of a native Chinese screening project and even guidelines.

The Value of Targeted Screening for Glaucoma: The University of Ilorin Teaching Hospital Experience.

BACKGROUND: Glaucoma is an irreversible silent and dangerous eye condition that leads to damage of the optic nerve head. This study aimed to determine the outcome of targeted glaucoma outreaches done in the University of Ilorin Teaching Hospital over three years with a view to early detection and timely institution of management. METHODS: The study is a retrospective review of 3 targeted hospital-based glaucoma screenings, World Sight Day of 2019 (140 participants), World Glaucoma Week of 2020 (176 participants), and World Glaucoma Week of 2022 (183 participants). The criteria for diagnosing glaucoma and glaucoma suspects were taken from the national study of prevalence and types of glaucoma from the Nigerian national blindness survey and International Society for Geographical and Epidemiological Ophthalmology criteria. RESULTS: The study population had a mean age of 45.54 years (SD 16.92) with individuals within the age group of 51-60 years comprising the majority of the participants (26.4%). Most participants had normal vision or mild visual impairment in the right eye (411, 86.1%) and left eye (405, 84.9%) while blindness was recorded in the right eye of 37 (7.7%) participants and left eye of 36 (7.5%). The prevalence of glaucoma cases and suspects among study participants was 29.4% and 42.5%, respectively. There was a statistically significant relationship between the diagnosis of glaucoma and older age, family history of glaucoma and elevated intraocular pressure. CONCLUSION: This study showed that targeted screening for glaucoma is an invaluable tool for ensuring early detection of the disease.

CONTEXTE: Le glaucome est une affection oculaire silencieuse et dangereuse qui entraîne des dommages au nerf optique. Cette étude visait à déterminer les résultats des campagnes de dépistage ciblé du glaucome menées à l'Hôpital universitaire d'Ilorin sur trois ans en vue d'un dépistage précoce et d'une institution rapide de la prise en charge. MÉTHODES: Cette étude est une revue rétrospective de trois dépistages hospitaliers ciblés du glaucome : la Journée mondiale de la vue de 2019 (140 participants), la Semaine mondiale du glaucome de 2020 (176 participants) et la Semaine mondiale du glaucome de 2022 (183 participants). Les critères de diagnostic du glaucome et des suspects de glaucome ont été tirés de l'étude nationale sur la prévalence et les types de glaucome de l'enquête nationale nigériane sur la cécité et des critères de la Société internationale de géographie et d'épidémiologie ophtalmologique. RÉSULTATS: La population étudiée avait un âge moyen de 45,54 ans (SD 16,92), les personnes âgées de 51 à 60 ans constituant la majorité des participants (26,4 %). La plupart des participants avaient une vision normale ou une légère déficience visuelle à l'œil droit (411, 86,1 %) et à l'œil gauche (405, 84,9 %), tandis que la cécité a été enregistrée à l'œil droit de 37 participants (7,7 %) et à l'œil gauche de 36 (7,5 %). La prévalence des cas de glaucome et des suspects de glaucome parmi les participants à l'étude était respectivement de 29,4 % et de 42,5 %. Il existait une relation statistiquement significative entre le diagnostic de glaucome et l'âge avancé, les antécédents familiaux de glaucome et l'élévation de la pression intraoculaire. CONCLUSION: Cette étude a montré que le dépistage ciblé du glaucome est un outil précieux pour assurer la détection précoce de la maladie. MOTS CLÉS: Dépistage du glaucome, Prévalence du glaucome, Cécité due au glaucome, Antécédents familiaux de glaucome.

49,XXXXY PATIENT AND INCIDENTAL FINDING OF LOW LEVEL MOSAIC 45,X IN THE MOTHER.

Context: 49,XXXXY syndrome is an aneuploidy that affects males and is commonly referred to as a variant of Klinefelter Syndrome. It presents a frequency of 1:85,000 to 100,000 births and an etiology related to non-disjunction of homologous chromosomes. Findings include skeletal abnormalities, hypogonadism, and cognitive impairment. Turner syndrome is also an aneuploidy of the sex chromosomes, which affects women, and has a prevalence of 1:2000 to 2500 births and a phenotype characterized by short stature and sexual infantilism. Objective: The objective of this article was to study the literature, investigate the family members and report the case. Subjects and Methods: Data collection was based on medical records, family history, karyotype analysis, and FISH analysis. Results: The karyotype of the proband revealed mos 49, XXXXY[45]/46, XY[5]. The patient's mother is affected by mosaic Turner Syndrome low level and the maternal grandmother by inversion of chromosome 9. The father, the younger brother, and the paternal grandmother present variations in the normality of their chromosomes. Conclusions: It is important to highlight that the early diagnosis of the syndrome and the initiation of therapy reduce biopsychosocial impairment. Investigation of other family members makes genetic counseling more effective.

Association between family history with lung cancer incidence and mortality risk in the Asia Cohort Consortium.

Family history of lung cancer (FHLC) has been widely studied but most prospective cohort studies have primarily been conducted in non-Asian countries. We assessed the association between FHLC with risk of lung cancer (LC) incidence and mortality in a population of East Asian individuals. A total of 478,354 participants from 11 population-based cohorts in the Asia Cohort Consortium were included. A Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 7,785 LC incident cases were identified. FHLC (any LC subtype) was associated with an increased risk of LC incidence (HR = 1.45, 95% CI = 1.30-1.63). The positive association was observed in men and women (HR = 1.44, 95% CI = 1.26-1.66 in men; HR = 1.47, 95% CI = 1.22-1.79 in women), and in both never-smokers and ever-smokers (HR = 1.43, 95% CI = 1.18-1.73 in never-smokers; HR = 1.46, 95% CI =1.27-1.67 in ever-smokers). FHLC was associated with an increased risk of lung adenocarcinoma (HR = 1.63, 95% CI: 1.36-1. 94), squamous cell carcinoma (HR = 1.88, 95% CI: 1.46-2.44), and other non-small cell LC (HR = 1.94, 95% CI: 1.02-3.68). However, we found no evidence of significant effect modification by sex, smoking status, and ethnic groups. In conclusion, FHLC was associated with increased risk of LC incidence and mortality, and the associations remained consistent regardless of sex, smoking status and ethnic groups among the East Asian population.

Motivators and Barriers to Joining a Lifestyle Change Program for Disease Prevention.

Introduction: Lifestyle change programs (LCPs) are effective in helping people adopt healthy lifestyles and maintain healthy weight for disease prevention. LCPs are known to be underutilized, but the nuances surrounding women's interest in using these programs for disease prevention need to be further explored so that enrollment and retention in these programs can be improved. Methods: The purpose of this study was to explore women's interest in and knowledge of LCPs and identify their motivators and barriers to joining these types of programs through a survey. The survey was administered both online and in person. The survey had 22 questions and included demographics, medical and family history, knowledge and interest in LCPs, and barriers and motivators to participating in LCPs. Results: Participants in this study included 1,606 women from 40 to 74 years of age. We found that respondents had limited knowledge about the benefits of LCPs in reducing risks of specific diseases, such as breast cancer and osteoarthritis. Respondents reported low-to-moderate interest in LCPs. We found that their interest in these programs was negatively associated with their weekly physical activity and positively associated with their body mass index (BMI) and the number of reported barriers to joining LCPs. The most common barriers cited were cost, location, time, and too many meetings. In addition, we found that respondents who had or were unsure about their family history of diabetes were more interested in LCPs compared with individuals who had no family history of diabetes. We did not find significant differences in respondent interest in LCPs across ethnicity. Conclusions: Our study suggests that specific barriers to LCPs-including women's knowledge of such programs-will need to be addressed before enrollment and retention in LCPs are increased.

Clinical characteristics of patients with a family history of psoriasis: an observational epidemiological study in Chinese Han population.

Introduction: Psoriasis, a chronic inflammatory skin disease, is believed to be influenced by both genetic and environmental factors. Despite this understanding, the clinical epidemiological status of psoriasis patients with a family history of the disease remains uncertain. Methods: In this study, we participated in a multicenter observational epidemiological study involved over 1,000 hospitals and enrolled a total of 5,927 psoriasis patients. These patients were categorized into two groups based on the presence or absence of a family history of psoriasis: family history cases (896) and sporadic cases (5,031). The clinical manifestations of these two groups were analyzed through clinical classification, comorbidities, treatment response, and other relevant factors. Results: The findings of our study indicate that individuals with a family history of psoriasis predisposition exhibit a notably elevated prevalence of psoriatic arthritis compared to those with sporadic occurrences. Moreover, patients with a family history of psoriasis display a more rapid and efficacious response to secukinumab. Additionally, individuals with moderate to severe psoriasis are at a heightened risk of developing cardiovascular and liver diseases in comparison to those with mild psoriasis, with no discernible impact of familial history on the likelihood of comorbidities. Discussion: Our study identified the clinical characteristics of individuals with a familial predisposition to psoriasis, offering novel insights into the management and therapeutic approaches for patients with this condition.

Anxiety and disease awareness in individuals with heredity for abdominal aortic aneurysm.

OBJECTIVE: The psychological consequences of being aware of an increased risk of developing abdominal aortic aneurysm as a first-degree relative of a person with abdominal aortic aneurysm are hitherto unexplored. This study investigates the awareness of heritability and anxiety in male and female adult offspring of abdominal aortic aneurysm patients compared to controls. Health-related quality of life among participants with aortic pathology was compared to participants with normal aortic diameters. METHODS: This was a cross-sectional point prevalence study based on the participants examined in the Detecting Abdominal Aortic Aneurysm in First Degree Relatives Trial (DAAAD; 752 adult offspring, 756 matched controls), 2020-2022. Questionnaires about health-related quality of life and study-specific questions regarding awareness of heritability were collected prior to the aortic ultrasound. RESULTS: Attendance rate was higher among individuals with heredity compared to controls (67% vs. 52%, p < 0.001). Of 1508 adult offspring examined, 65% reported having a close relative with abdominal aortic aneurysm (6% in controls). Female adult offspring reported higher awareness of heritability than controls (38% vs. 12%, p < 0.001), as did males (32% vs. 8%, p < 0.001). A slight majority of participants with awareness reported anxiety (54% of female offspring; 51% of male). There were no measured differences in health-related quality of life between the groups when standard health-related quality of life instruments were used. CONCLUSION: The higher-than-expected proportion of adult offspring with awareness of heritability and anxiety about such risk indicates that we fail to communicate risk to this group appropriately via the current channels of information within the healthcare system. This calls for the development of dedicated strategies for improved communication of abdominal aortic aneurysm risk to patients and their next of kin.

A 12-year comparison of patients with Alzheimer's dementia with their informants in eight Asian countries.

BACKGROUND: The number of patients with Alzheimer's disease (AD) has increased dramatically in Asia. OBJECTIVE: To update the demographic characteristics of patients with AD and their informants in eight Asian countries and compare them from 12 years prior. METHODS: The A1-A3 components of the Uniform Dataset (UDS), version 3.0, were administered in Taiwan, Beijing, Hong Kong, Korea, Japan, Philippines, Thailand, and Indonesia. Data were compared with patients with AD in the first registration using the UDS version 1.0 from 2010-2014 in the same regions. RESULTS: A total of 1885 patients with AD and their informants were recruited from 2022 to 2024 and were compared with 2042 patients recruited a decade prior. Each country had its own unique characteristics that changed between both eras. The mean age of the patients and informants was 79.8±8.2 years and 56.5±12.1 years, respectively. Compared with the first registration, the patients were older (79.8 vs 79.0, p=0.002) and had worse global function (mean CDR-SB scores 6.1 vs 5.8, p<0.001); more informants were children (56 % vs. 48 %, p<0.001), and their frequency of in-person visits increased significantly if not living together. A total of 11 %, 4.5 %, 11 %, and 0.4 % of the patients had a reported history of cognitive impairment in their mothers, fathers, siblings, and children, respectively; all percentages, except children, increased significantly over the past decade. CONCLUSION: The present study reports the heterogeneous characteristics of patients with AD and their informants in Asian countries, and the distinct changes in the past decade. The differences in dementia evaluation and care between developing and developed countries warrant further investigation.

Effect of family history of cancer on postoperative survival in patients with non-small cell lung cancer.

Background: Family history of cancer (FHC) has been reported to increase mortality of non-small cell lung cancer, mainly comprised of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). However, the impact of FHC on long-term survival remains controversial. This study aims to identify the impact of FHC on postoperative survival in LUAD and LUSC. Methods: Patients underwent lung resection for LUAD or LUSC in West China Hospital from 2009 to 2021 were enrolled. The 5-year overall survival (OS), lung cancer-specific survival (LCSS) and progression-free survival (PFS) were compared between the patients with and without FHC. Multivariable Cox regression was also performed. Results: A total of 6,253 patients were enrolled, including 5,685 LUAD and 568 LUSC. Altogether 18.9% (1,077/5,685) patients had FHC in LUAD, and 12.7% (72/568) patients had FHC in LUSC. In LUAD, the patients with FHC showed comparable survival compared with the patients without FHC regarding 5-year OS (87.9% vs. 86.5%, P=0.49), 5-year PFS (84.8% vs. 80.9%, P=0.06), and 5-year LCSS (89.2% vs. 88.0%, P=0.96). In LUSC, the patients with FHC had poorer survival compared with the patients without FHC according to 5-year OS (40.9% vs. 68.2%, P=0.007), 5-year PFS (42.3% vs. 66.2%, P=0.003), and 5-year LCSS (45.8% vs. 72.7%, P=0.003). Multivariate analyses indicated that FHC was an independent prognostic factor of OS, PFS, and LCSS in the patients with LUSC. Conclusions: FHC was associated with a poor survival after lung resection in LUSC not LUAD patients. More attention should be paid in postoperative monitoring and treatment in LUSC patients with FHC.

Family History in Parkinson's Disease: A National Cross-Sectional Study.

BACKGROUND: Family history of Parkinson's disease (PD) is a common finding in PD patients. However, a few studies have systematically examined this aspect. OBJECTIVES: We investigated the family history of PD patients, comparing demographic and clinical features between familial PD (fPD) and sporadic PD (sPD). METHODS: A cross-sectional study enrolling 2035 PD patients was conducted in 28 Italian centers. Clinical data and family history up to the third degree of kinship were collected. RESULTS: Family history of PD was determined in 21.9% of patients. fPD patients had earlier age at onset than sporadic patients. No relevant differences in the prevalence of motor and nonmotor symptoms were detected. Family history of mood disorders resulted more prevalently in the fPD group. CONCLUSIONS: fPD was found to recur more frequently than previously reported. Family history collection beyond the core family is essential to discover disease clusters and identify novel risk factors for PD.

Prevalence of Germline Pathogenic Variants in Renal Cancer Predisposition Genes in a Population-Based Study of Renal Cell Carcinoma.

Renal cell carcinoma (RCC) has been associated with germline pathogenic or likely pathogenic (PLP) variants in recognised cancer susceptibility genes. Studies of RCC using gene panel sequencing have been highly variable in terms of study design, genes included, and reported prevalence of PLP variant carriers (4-26%). Studies that restricted their analysis to established RCC predisposition genes identified variants in 1-6% of cases. This work assessed the prevalence of clinically actionable PLP variants in renal cancer predisposition genes in an Australian population-based sample of RCC cases. Germline DNA from 1029 individuals diagnosed with RCC who were recruited through the Victoria and Queensland cancer registries were screened using a custom amplicon-based panel of 21 genes. Mean age at cancer diagnosis was 60 ± 10 years, and two-thirds (690, 67%) of the participants were men. Eighteen participants (1.7%) were found to carry a PLP variant. Genes with PLP variants included BAP1, FH, FLCN, MITF, MSH6, SDHB, TSC1, and VHL. Most carriers of PLP variants did not report a family history of the disease. Further exploration of the clinical utility of gene panel susceptibility testing for all RCCs is warranted.

Comparison of isometric handgrip test among pregnant offspring of hypertensive parents and pregnant offspring of non-hypertensive parents.

Context: A family history of hypertension is one of the important risk factors for the development of pregnancy-induced hypertension (PIH). Offspring of hypertensive parents should be screened for PIH. The isometric handgrip (IHG) test is used to assess autonomic function among them. Autonomic function dysregulation can indicate their predisposition to develop PIH later in the course of pregnancy. Aim and Objectives: To compare the IHG among pregnant offspring of hypertensive parents (Group 1) and non-hypertensive parents (Group 2). Methods and Materials: This is a cross-sectional study done among 100 pregnant women in the second trimester (50 participants in each group). Blood pressure responses to sustained hand grip for 2 minutes of maximum voluntary contraction (MVC) were recorded, immediately at the end of the IHG test and after 5 minutes of the IHG test. Statistical Analysis: Independent t-test and Mann-Whitney U test were used to compare the responses in two groups. Results: There is no statistical difference in basal blood pressure and heart rate between the two groups. Group 1 exhibited a significant increase in systolic blood pressure (SBP) and diastolic blood pressure (DBP) compared to Group 2 immediately after 2 minutes of the IHG test. There is a significant increase in SBP after 5 minutes of the IHG in Group 2. Conclusions: Offspring of hypertensive parents have increased sympathetic reactivity and restoration of the blood pressure is significantly less compared to offspring of normotensive parents, which may predispose them for PIH. IHG can be applied as a convenient tool to screen the population who are at risk of PIH in places like primary health centres or field screenings where IHG is one possible option.

Clinical Characteristics of Patients with De Novo Parkinson's Disease and a Positive Family History.

Background/Objectives: A family history of Parkinson's disease (PD) is an important risk factor for developing PD. Because only a few studies have investigated the clinical characteristics of PD patients based on family history, this study compared the clinical characteristics of PD patients with and without a family history of PD. Methods: The study involved 356 patients with de novo PD. The data on the patients' PD family histories were obtained from the patients and their caregivers. Motor and non-motor PD symptoms were assessed using the appropriate scales. Results: Out of the 356 PD patients, 26 (7.3%) had a family history of PD. Compared with patients without a family history of PD, those with a family history of PD tended to be younger at diagnosis (67.9 years vs. 62.2 years, respectively; p = 0.009) and exhibited significantly more severe rigidity (p = 0.036). Motor subtype was not different between the PD patients with and without a family history. PD patients with a family history experienced significantly fewer falls/cardiovascular symptoms within the Non-Motor Symptoms Scale domains (p = 0.001) compared to their counterparts, although this was not statistically significant upon adjusting for age (p = 0.119). Conclusions: In de novo PD patients, having a family history of PD is associated with a younger age at diagnosis and more severe rigidity.

First-degree family history of cancers in patients with stage I endometrial carcinoma. Prevalence and prognostic impact.

BACKGROUND: We aimed to study the impact of first-degree family history on patients with endometrial cancer. METHODS: We conducted a retrospective chart review from January 1990 to June 2016, comparing stage I endometrial cancer patients with and without a sporadic family history of cancers. We collected the patients' demographic information, tumor characteristics, and treatment plans. During the follow-up period, patient information on tumor recurrence and survival was collected. The chi-square test was used to assess the associations between categorical variables. The Cox proportional hazards regression model was used to estimate multivariate-adjusted hazard ratios (95% confidence interval (CI)). RESULTS: Among the 1737 patients with stage I endometrial cancer, 709 had a positive first-degree family history of cancers and 1028 had negative family history (FH) of cancers. Patients with positive FH were more likely to be older, have stage IB disease, and receive adjuvant radiotherapy; however, the difference was not statistically significant. At 5 years follow up, patients with a positive family history had longer time to recurrence (TTR) than their negative FH counterparts. Maternal family history of cancer was the most common, followed by a sister's history of cancer, paternal history, brother's history, and offspring history of cancer. Breast, endometrial, and colon cancers are the most common cancers among first-degree relatives. CONCLUSION: Endometrial cancer patients with sporadic first-degree FH of cancers share similar demographics and tumor characteristics compared to their counterpart with slightly increased likelihood to be older, with stage IB disease and have a longer TTR compared to their negative counterpart.

The impact of family cancer history on tumor metabolism and prognosis in patients with non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality, and the role of family cancer history in disease progression and treatment response remains underexplored. This study aims to investigate the influence of family tumor history on disease-free survival, tumor metabolism, and treatment response in NSCLC patients. A retrospective, single-center study of 414 NSCLC patients was conducted, with 101 patients having a family history of cancer (FHC). Disease-free survival (DFS), tumor glucose metabolism assessed by 18F-FDG PET/CT, and treatment response to chemoradiotherapy, targeted therapy, and immunotherapy were analyzed. Multivariate modeling was performed to improve prognostic prediction. Patients with FHC exhibited higher TNM staging, increased susceptibility to lymph node invasion, and elevated tumor glucose metabolism levels. Family history of cancer, particularly colorectal and lung cancer, was a significant risk factor for disease-free survival. Targeted therapy and immunotherapy significantly improved patient prognosis, while family history of cancer affected the efficacy of chemoradiotherapy but not targeted therapy or immunotherapy. Multivariate modeling combining FHC, treatment, and tumor metabolism levels yielded improved predictive performance. Our study highlights the importance of considering a patient's family history when assessing risk profiles and formulating treatment decisions for NSCLC patients. Further research is needed to understand the molecular mechanisms underlying these observed associations and to develop more effective treatment strategies for NSCLC patients with a cancer family history.

Healthy First-Degree Relatives From Multiplex Families vs Simplex Families Have a Higher Subclinical Intestinal Inflammation, a Distinct Fecal Microbial Signature, and Harbor a Higher Risk of Developing Crohn's Disease.

BACKGROUND & AIMS: Unaffected first-degree relatives (FDRs) from families with ≥2 affected FDRs with Crohn's disease (CD, multiplex families) have a high risk of developing CD, although the underlying mechanisms driving this risk are poorly understood. We aimed to identify differences in biomarkers between FDRs from multiplex vs simplex families and investigate the risk of future CD onset accounting for potential confounders. METHODS: We assessed the Crohn's and Colitis Canada Genetic Environmental Microbial cohort of healthy FDRs of patients with CD. Genome-wide CD-polygenic risk scores, urinary fractional excretion of lactulose-to-mannitol ratio, fecal calprotectin (FCP), and fecal 16S ribosomal RNA microbiome were measured at recruitment. Associations between CD multiplex status and baseline biomarkers were determined using generalized estimating equations models. Cox models were used to assess the risk of future CD onset. RESULTS: There were 4051 participants from simplex families and 334 from CD multiplex families. CD multiplex status was significantly associated with higher baseline FCP (P = .026) but not with baseline CD-polygenic risk scores or the lactulose-to-mannitol ratio. Three bacterial genera were found to be differentially abundant between both groups. CD multiplex status at recruitment was independently associated with an increased risk of developing CD (adjusted hazard ratio, 3.65; 95% confidence interval, 2.18-6.11, P < .001). CONCLUSION: Within FDRs of patients with CD, participants from multiplex families had a 3-fold increased risk of CD onset, a higher FCP, and an altered bacterial composition, but not genetic burden or altered gut permeability. These results suggest that putative environmental factors might be enriched in FDRs from multiplex families.

3-generation family histories of mental, neurologic, cardiometabolic, birth defect, asthma, allergy, and autoimmune conditions associated with autism: An open-source catalog of findings.

The relatively few conditions and family member types (e.g., sibling, parent) considered in investigations of family health history in autism spectrum disorder (ASD, or autism) limits understanding of the role of family history in autism etiology. For more comprehensive understanding and hypothesis-generation, we produced an open-source catalog of autism associations with family histories of mental, neurologic, cardiometabolic, birth defect, asthma, allergy, and autoimmune conditions. All live births in Denmark, 1980-2012, of Denmark-born parents (1,697,231 births), and their 3-generation family members were followed through April 10, 2017 for each of 90 diagnoses (including autism), emigration or death. Adjusted hazard ratios (aHR) were estimated via Cox regression for each diagnosis-family member type combination, adjusting for birth year, sex, birth weight, gestational age, parental ages at birth, and number of family member types of index person; aHRs also calculated for sex-specific co-occurrence of each disorder. We obtained 6462 individual family history aHRS across autism overall (26,840 autistic persons; 1.6% of births), by sex, and considering intellectual disability (ID); and 350 individual co-occurrence aHRS. Results are cataloged in interactive heat maps and down-loadable data files: https://ncrr-au.shinyapps.io/asd-riskatlas/ and interactive graphic summaries: https://public.tableau.com/app/profile/diana.schendel/viz/ASDPlots_16918786403110/e-Figure5. While primarily for reference material or use in other studies (e.g., meta-analyses), results revealed considerable breadth and variation in magnitude of familial health history associations with autism by type of condition, family member type, sex of the family member, side of the family, sex of the index person, and ID status, indicative of diverse genetic, familial, and nongenetic autism etiologic pathways. Careful attention to sources of autism likelihood in family health history, aided by our open data resource, may accelerate understanding of factors underlying neurodiversity.

Prevalence of Non-communicable Disease Risk Factors Among Adults in a Rural Field Practice Area of a Tertiary Care Medical Center in Karnataka.

Background Non-communicable diseases (NCDs), also referred to as chronic diseases, typically have a long duration and arise from a combination of genetic, physiological, environmental, and behavioral factors. Each year, 17 million people under the age of 70 die from non-communicable diseases (NCDs), with 86% of these premature deaths occurring in low- and middle-income countries. Objectives To estimate the prevalence of NCD risk factors among adults (18-65 years) in a rural population. Methods A cross-sectional study was conducted by selecting 200 participants from 200 households using convenience sampling. Participants aged 18-65 years were included, and locked households were excluded. Sociodemographic profiles were assessed using semi-structured questionnaires, and NCD risk factors were assessed using a Community-Based Assessment Checklist (CBAC). Descriptive statistics and associations were analyzed. Results The majority of participants were men (53.5%), married (89.5%), and belonged to the class 2 socioeconomic classification. The prevalence of NCD risk factors was 17%, with smoking (12.5%), alcohol consumption (6%), and waist circumference (1.8% for men and 27.9% for women) being the most common risk factors. Older age, lower educational attainment, unemployment, and lower-income classes were associated with a higher risk of NCDs. Conclusion The study identifies key risk factors for non-communicable diseases (NCDs) as family history, waist circumference over 90 cm, daily alcohol consumption, and tobacco use, all significantly increasing the risk. Physical activity under 150 minutes per week and occupational exposure to crop residue showed no significant effect.

Family history and genetic risk score combined to guide cancer risk stratification: A prospective cohort study.

Family history (FH) of cancer and polygenic risk scores (PRS) are pivotal for cancer risk assessment, yet their combined impact remains unclear. Participants in the UK Biobank (UKB) were recruited between 2006 and 2010, with complete follow-up data updated until February 2020 for Scotland and January 2021 for England and Wales. Using UKB data (N = 442,399), we constructed PRS and incidence-weighted overall cancer PRS (CPRS). FH was assessed through self-reported standardized questions. Among 202,801 men (34.6% with FH) and 239,598 women (42.0% with FH), Cox regression was used to examine the associations between FH, PRS, and cancer risk. We found a significant dose-response relationship between FH of cancer and corresponding cancer risk (Ptrend < .05), with over 10 significant pairs of cross-cancer effects of FH. FH and PRS are positively correlated and independent. Joint effects of FH of cancer (multiple cancers) and PRS (CPRS) on corresponding cancer risk were observed: for instance, compared with participants with no FH of cancer and low PRS, men with FH of cancer and high PRS had the highest risk of colorectal cancer (hazard ratio [HR]: 3.69, 95% confidence interval [CI]: 3.01-4.52). Additive interactions were observed in prostate and overall cancer risk for men and breast cancer for women, with the most significant result being a relative excess risk of interaction (RERI) of 2.98, accounting for ~34% of the prostate cancer risk. In conclusion, FH and PRS collectively contribute to cancer risk, supporting their combined application in personalized risk assessment and early intervention strategies.