Family History Information Research Articles

Bringing personalized medicine to the community through public engagement.

There is growing expectation that advances in genomics herald the age of personalized medicine. Medicine has always been personal; however, the growing availability of genomic tools and technologies enable more precise risk stratification and disease management than ever before. Notably, a key aspect of the success of personalized medicine is related to public acceptance and engagement. For example, the public must be willing to collect and utilize family history and other genomic information, and individuals must be able to interpret and comprehend the significance of genomic information for their health and well-being. In this article, we review public engagement initiatives with personalized medicine, outline some of the challenges to engaging the public with personalized and genomic medicine and offer suggestions for future engagement initiatives. As genomic advances continue, the need for public input in the development of appropriate institutional practices and public policy about personalized medicine is ever important.

PTH-005 Verifying Patient Reported Family History in the Colorectal Family History Screening Clinic (CFHSC)

IntroductionNational Colorectal Family History Screening guidelines categorise risk based on incidence of familial cancer, type of cancer, age and genetic proximity. High and Medium risk patients are recommended regular or...

Nurses' attitudes, abilities and educational preference related to using family pedigrees in clinical practice

There is growing worldwide interest in using family pedigrees to assess health risks for diseases and implementing potential preventive interventions for health promotion. Nurses have been identified as key professionals in the process of collecting family history information and constructing pedigrees, and there is a gap in the literature related to these activities. The purpose of this study was to determine nurses' knowledge about, attitudes towards, perceived ability to use, and educational preference related to inclusion of family pedigrees in clinical practice. The study utilized a survey method with 174 nurses and correlational descriptive design. Results showed 74% of the nurses were interested in learning about family pedigrees and 64% responded positively to including them in clinical practice with the belief by 88% that they are helpful for preventive health care. Findings may be used to advance education and utilization of family pedigrees for nurses in clinical practice.

Using web-based familial risk information for diabetes prevention: a randomized controlled trial

BackgroundIt has been suggested that family history information may be effective in motivating people to adopt health promoting behaviour. The aim was to determine if diabetic familial risk information by using a web-based tool leads to improved self-reported risk-reducing behaviour among individuals with a diabetic family history, without causing false reassurance among those without a family history.MethodsAn online sample of 1,174 healthy adults aged 35–65 years with a BMI ≥ 25 was randomized into two groups receiving an online diabetes risk assessment. Both arms received general tailored diabetes prevention information, whilst the intervention arm also received familial risk information after completing a detailed family history questionnaire. Separate analysis was performed for four groups (family history group: 286 control versus 288 intervention group; no family history: 269 control versus 266 intervention group). Primary outcomes were self-reported behavioural outcomes: fat intake, physical activity, and attitudes towards diabetes testing. Secondary outcomes were illness and risk perceptions.ResultsFor individuals at familial risk there was no overall intervention effect on risk-reducing behaviour after three months, except for a decrease in self-reported saturated fat intake among low-educated individuals (Beta (b) -1.01, 95% CI −2.01 to 0.00). Familial risk information resulted in a decrease of diabetes risk worries (b −0.21, -0.40 to −0.03). For individuals without family history no effect was found on risk-reducing behaviour and perceived risk. A detailed family history assessment resulted in a greater percentage of individuals reporting a familial risk for diabetes compared to a simple enquiry.ConclusionsWeb-based familial risk information reduced worry related to diabetes risk and decreased saturated fat intake of those at greatest need of preventative care. However, the intervention was not effective for the total study population on improving risk-reducing behaviour. The emphasis on familial risk does not seem to result in false reassurance among individuals without family history. Additionally, a detailed family history questionnaire identifies more individuals at familial risk than a simple enquiry.Trial registrationNTR1938

Self-reported family history of leiomyoma: not a reliable marker of high risk

PurposeTo examine the importance of self-reported family history of uterine leiomyoma (fibroids) as a marker of risk. MethodsWomen, aged 35 to 49, were randomly selected from the membership of a large, urban health plan. Participants completed a self-administered questionnaire about family history of fibroids. Ultrasound screening for fibroids followed, regardless of whether participants had been previously diagnosed (660 black, 412 white). Data for each ethnic group were analyzed separately using Poisson regression. ResultsIn both ethnic groups, women who reported a family history of fibroids had an elevated risk of fibroids compared with those without family history. However, no elevated risk was apparent for cases who did not know they had fibroids when they reported the family history information. ConclusionsMany women may first learn about their family history of fibroids when discussing their own clinical diagnosis with family members. Such bias would invalidate self-reported family history as a predictor of fibroid risk. As new pharmacologic treatments for fibroids are developed, women at high risk of fibroids would benefit from early screening and pharmacologic treatment to delay development of large fibroids and reduce the need for invasive treatments. Self-reported family history is not useful for identifying high-risk women.

Clinical predictors of genetic testing outcomes in hypertrophic cardiomyopathy

Genetic testing for hypertrophic cardiomyopathy has been commercially available for almost a decade; however, low mutation detection rate and cost have hindered uptake. This study sought to identify clinical variables that can predict probands with hypertrophic cardiomyopathy in whom a pathogenic mutation will be identified. Probands attending specialized cardiac genetic clinics across Australia over a 10-year period (2002-2011), who met clinical diagnostic criteria for hypertrophic cardiomyopathy and who underwent genetic testing for hypertrophic cardiomyopathy were included. Clinical, family history, and genotype information were collected. A total of 265 unrelated individuals with hypertrophic cardiomyopathy were included, with 138 (52%) having at least one mutation identified. The mutation detection rate was significantly higher in the probands with hypertrophic cardiomyopathy with an established family history of disease (72 vs. 29%, P < 0.0001), and a positive family history of sudden cardiac death further increased the detection rate (89 vs. 59%, P < 0.0001). Multivariate analysis identified female gender, increased left-ventricular wall thickness, family history of hypertrophic cardiomyopathy, and family history of sudden cardiac death as being associated with greatest chance of identifying a gene mutation. Multiple mutation carriers (n = 16, 6%) were more likely to have suffered an out-of-hospital cardiac arrest or sudden cardiac death (31 vs. 7%, P = 0.012). Family history is a key clinical predictor of a positive genetic diagnosis and has direct clinical relevance, particularly in the pretest genetic counseling setting.

Heritability and sibling recurrent risk of developmental dysplasia of the hip in Chinese population

Previous familial segregation studies supported that developmental dysplasia of the hip (DDH) is a multifactorial genetic disease. However, the exact extent of genetic effects has not been fully evaluated, especially in Asian population. The aim of this study is to estimate the sibling recurrent risk and heritability of DDH in a large Chinese cohort. Four hundred and twenty-nine DDH probands and 534 matched normal controls were recruited from a screening programme for DDH, including 628 siblings in families of probands and 889 siblings in those of controls, respectively. The detailed information of family history was obtained, and the prevalence of DDH among siblings of probands, as well as controls, was determined. The sibling recurrent risk and heritability was estimated using classical liability threshold model. Eighty-seven siblings (13.85%) in families of proband and 14 siblings (1.57%) in normal control families were diagnosed as DDH. The recurrent risk in siblings of probands was at least tenfolds that in siblings of controls. Compared with the normal controls, the sibling recurrent risk was about 12-fold increase in male sib, and 9-fold increase in female sib. Overall, a high heritability of 83.59 ± 4.90% (h(2) ± SE) was observed. When stratified by genders, it was even higher for female siblings (91.02 ± 7.25%). This study for the first time exhibits a high sibling recurrent risk and heritability for DDH in Asian population. It also shows there is a high probability to identify the underlying predisposition genes in future genetic study.

An inexpensive family index of risk for mood issues improves identification of pediatric bipolar disorder.

Family history of mental illness provides important information when evaluating pediatric bipolar disorder (PBD). However, such information is often challenging to gather within clinical settings. This study investigates the feasibility and utility of gathering family history information using an inexpensive method practical for outpatient settings. Families (N=273) completed family history, rating scales, and the Mini-International Neuropsychiatric Interview (Sheehan et al., 1998) and the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children (Kaufman et al., 1997) about youths 5-18 (median=11) years of age presenting to an outpatient clinic. Primary caregivers completed a half-page Family Index of Risk for Mood issues (FIRM). All families completed the FIRM quickly and easily. Most (78%) reported 1+ relatives having a history of mood or substance issues (M=3.7, SD=3.3). A simple sum of familial mood issues discriminated cases with PBD from all other cases (area under receiver operating characteristic [AUROC]=.63, p=.006). FIRM scores were specific to youth mood disorder and not attention-deficit/hyperactivity disorder or disruptive behavior disorder. FIRM scores significantly improved the detection of PBD even controlling for rating scales. No subset of family risk items performed better than the total. Family history information showed clinically meaningful discrimination of PBD. Two different approaches to clinical interpretation showed validity in these clinically realistic data. Inexpensive and clinically practical methods of gathering family history can help to improve the detection of PBD.

Using a state cancer registry to recruit young breast cancer survivors and high-risk relatives: protocol of a randomized trial testing the efficacy of a targeted versus a tailored intervention to increase breast cancer screening

BackgroundThe Michigan Prevention Research Center, the University of Michigan Schools of Nursing, Public Health, and Medicine, and the Michigan Department of Community Health propose a multidisciplinary academic-clinical practice three-year project to increase breast cancer screening among young breast cancer survivors and their cancer-free female relatives at greatest risk for breast cancer.Methods/designThe study has three specific aims: 1) Identify and survey 3,000 young breast cancer survivors (diagnosed at 20–45 years old) regarding their breast cancer screening utilization. 2) Identify and survey survivors’ high-risk relatives regarding their breast cancer screening utilization. 3) Test two versions (Targeted vs. Enhanced Tailored) of an intervention to increase breast cancer screening among survivors and relatives. Following approval by human subjects review boards, 3,000 young breast cancer survivors will be identified through the Michigan Cancer Registry and mailed an invitation letter and a baseline survey. The baseline survey will obtain information on the survivors’: a) current breast cancer screening status and use of genetic counseling; b) perceived barriers and facilitators to screening; c) family health history. Based on the family history information provided by survivors, we will identify up to two high-risk relatives per survivor. Young breast cancer survivors will be mailed consent forms and baseline surveys to distribute to their selected high-risk relatives. Relatives’ baseline survey will obtain information on their: a) current breast cancer screening status and use of genetic counseling; and b) perceived barriers and facilitators to screening. Young breast cancer survivors and high-risk relatives will be randomized as a family unit to receive two versions of an intervention aiming to increase breast cancer screening and use of cancer genetic services. A follow-up survey will be mailed 9 months after the intervention to survivors and high-risk relatives to evaluate the efficacy of each intervention version on: a) use of breast cancer screening and genetic counseling; b) perceived barriers and facilitators to screening; c) self-efficacy in utilizing cancer genetic and screening services; d) family support related to screening; e) knowledge of breast cancer genetics; and f) satisfaction with the intervention.DiscussionThe study will enhance efforts of the state of Michigan surrounding cancer prevention, control, and public health genomics.Trial registrationNCT01612338

Proposed roadmap to stepwise integration of genetics in family medicine and clinical research

We propose A step-by-step roadmap to integrate genetics in the Electronic Patient Record in Family Medicine and clinical research. This could make urgent operationalization of readily available genetic knowledge feasible in clinical research and consequently improved medical care.Improving genomic literacy by training and education is needed first. The second step is the improvement of the possibilities to register the family history in such a way that queries can identify patients at risk. Adding codes to the ICPC chapters “A21 Personal/family history of malignancy” and “A99 Disease carrier not described further” is proposed. Multidisciplinary guidelines for referral must be unambiguous. Electronical patient records need possibilities to add (new) family history information, including links between individuals who are family members. Automatic alerts should help general practitioners to recognize patients at risk who satisfy referral criteria. We present a familial breast cancer case with a BRCA1 mutation as an example.

Use of a Web-based Risk Appraisal Tool for Assessing Family History and Lifestyle Factors in Primary Care

Primary care clinicians can play an important role in identifying individuals at increased risk of cancer, but often do not obtain detailed information on family history or lifestyle factors from their patients. We evaluated the feasibility and effectiveness of using a web-based risk appraisal tool in the primary care setting. Five primary care practices within an academic care network were assigned to the intervention or control group. We included 15,495 patients who had a new patient visit or annual exam during an 8-month period in 2010-2011. Intervention patients were asked to complete a web-based risk appraisal tool on a laptop computer immediately before their visit. Information on family history of cancer was sent to their electronic health record (EHR) for clinicians to view; if accepted, it populated coded fields and could trigger clinician reminders about colon and breast cancer screening. The main outcome measure was new documentation of a positive family history of cancer in coded EHR fields. Secondary outcomes included clinician reminders about screening and discussion of family history, lifestyle factors, and screening. Among eligible intervention patients, 2.0% had new information on family history of cancer entered in the EHR within 30 days after the visit, compared to 0.6% of eligible control patients (adjusted odds ratio = 4.3, p = 0.03). There were no significant differences in the percent of patients who received moderate or high risk reminders for colon or breast cancer screening. Use of this tool was associated with increased documentation of family history of cancer in the EHR, although the percentage of patients with new family history information was low in both groups. Further research is needed to determine how risk appraisal tools can be integrated with workflow and how they affect screening and health behaviors.

Using genetic information from candidate gene and genome-wide association studies in risk prediction for alcohol dependence.

Family-based and genome-wide association studies (GWAS) of alcohol dependence (AD) have reported numerous associated variants. The clinical validity of these variants for predicting AD compared with family history information has not been reported. Using the Collaborative Study on the Genetics of Alcoholism (COGA) and the Study of Addiction: Genes and Environment (SAGE) GWAS samples, we examined the aggregate impact of multiple single nucleotide polymorphisms (SNPs) on risk prediction. We created genetic sum scores by adding risk alleles associated in discovery samples, and then tested the scores for their ability to discriminate between cases and controls in validation samples. Genetic sum scores were assessed separately for SNPs associated with AD in candidate gene studies and SNPs from GWAS analyses that met varying P-value thresholds. Candidate gene sum scores did not exhibit significant predictive accuracy. Family history was a better classifier of case-control status, with a significant area under the receiver operating characteristic curve (AUC) of 0.686 in COGA and 0.614 in SAGE. SNPs that met less stringent P-value thresholds of 0.01-0.50 in GWAS analyses yielded significant AUC estimates, ranging from mean estimates of 0.549 for SNPs with P < 0.01 to 0.565 for SNPs with P < 0.50. This study suggests that SNPs currently have limited clinical utility, but there is potential for enhanced predictive ability with better understanding of the large number of variants that might contribute to risk.

Improving identification of lynch syndrome patients: A comparison of research data with clinical records

Current evidence suggests poor identification and referral of Lynch syndrome patients. This study evaluated the strategies by which patients with endometrial cancer were referred to genetics services. Data from clinic-based patients with endometrial cancer enrolled through the Australian National Endometrial Cancer population-based research study with detailed family history information were analyzed. The Amsterdam II criteria, the revised Bethesda guidelines, and criteria adapted for this study was assessed using personal/family history information. The percentages of patients referred and who could have been referred to genetics services, and the performance of each criterion for identifying possible mismatch-repair (MMR) gene mutation carriers, based on tumor MMR immunohistochemistry (IHC), were determined. Research data indicated that 236/397(59%) of patients with endometrial cancer had family/personal history of cancer, including 14 (4%) who fulfilled Amsterdam II criteria. Family history information was noted in the hospital records for only 61(15%) patients, including 7/14 (50%) of patients meeting Amsterdam criteria, and always less extensively than that recorded in the research setting. Only 13 patients (two meeting Amsterdam criteria) were referred for genetic assessment. Of 58 patients with tumor MMR protein-IHC loss, the Amsterdam criteria and Bethesda guidelines identified only three and 34% of these possible germline mutation carriers, respectively. Greater sensitivity (60%) was obtained using a single criterion proposed by our study, ≥2 first-degree or second-degree relatives reporting Lynch cancers. Hospital records indicate poor recognition of family history. Application of research methods show improved identification and may facilitate appropriate referrals of endometrial cancer patients with possible Lynch syndrome.

Family History: Impact on Coronary Heart Disease Risk Assessment beyond Guideline-Defined Factors

Objective: Family history (FH) provides insights into the effects of shared genomic susceptibilities, environments and behaviors, making it a potentially valuable risk assessment tool for chronic diseases. We assessed whether coronary heart disease (CHD) risk assessment is improved when FH information is added to other clinical information recommended in guidelines. Methods: We applied logistic regression analyses to cross-sectional data originally obtained from a UK study of women who delivered a live-born infant between 1951 and 1970. We developed 3 models: Model 1 included only the covariates in a guideline applicable to the population, Model 2 added FH to Model 1, and Model 3 included a fuller range of risk factors. For each model, its ability to discriminate between study subjects with and those without CHD was evaluated and its impact on risk classification examined using the net reclassification index. Results: FH was an independent risk factor for CHD (odds ratio = 1.7, 95% confidence interval = 1.26-2.47) and improved discrimination beyond guideline-defined clinical factors (p < 0.0006). However, the difference in the area under the curve of 2.8% and the extent of patient reclassification resulting from the inclusion of FH were small (p = 0.11). Conclusion: While FH were a significant independent risk factor for CHD, it added little to risk factors typically included in guidelines.

From Citizens to Enemy Aliens: Oregon Women, Marriage, and the Surveillance State during the First World War

Between the days of June 17 and June 26, 1918, Oregon government officials under U.S. Presidential Proclamation collected family and work history information, photographs, and finger prints of 1,484 women from across the state of Oregon. These women were considered “enemy aliens” because they had emigrated from Germany, or, as was the case for 394 of these women, because they married German men thereby forfeiting their U.S. Citizenship. In this article, historian Kimberly Jensen brings to life this collection of Female Enemy Alien Registration records. During a time when a woman's citizenship relied on that of her husband's, Jensen reveals the expressions of life, character, and subtle forms of protest among the registration records of file boxes in the Oregon Historical Society Research Library collections.

From Citizens to Enemy Aliens: Oregon Women, Marriage, and the Surveillance State during the First World War

Between the days of June 17 and June 26, 1918, Oregon government officials under U.S. Presidential Proclamation collected family and work history information, photographs, and finger prints of 1,484 women from across the state of Oregon. These women were considered “enemy aliens” because they had emigrated from Germany, or, as was the case for 394 of these women, because they married German men thereby forfeiting their U.S. Citizenship. In this article, historian Kimberly Jensen brings to life this collection of Female Enemy Alien Registration records. During a time when a woman's citizenship relied on that of her husband's, Jensen reveals the expressions of life, character, and subtle forms of protest among the registration records of file boxes in the Oregon Historical Society Research Library collections.

Association of family history and consanguinity with permanent hearing impairment

Background: Risk factors for hearing impairment can offer important information for both the family and health-care providers regarding etiology, other associated health problems, and risk of recurrence in sub-sequent pregnancy. Family history and consanguinity indicates the possible involvement of genetic factors. Objective: The aim of the study is to find the strength of association of family history and consanguinity with permanent hearing impairment in infants. Materials and Methods: A case-control study was designed on 420 infants with permanent hearing impairment and normal hearing from the year 2008 to 2012. The case control ratio was 1:1. Alternate sampling method was used in a hospital for selecting the control group. Parent interview was carried out to collect the information of family history of hearing impairment and consanguineous marriage. Results: Family history and consanguinity was seen in 18.6% and 39.5% of the hearing-impaired group. These factors were associated with hearing impairment with a high significance (odds ratio (OR) 6.5; 95% Confidence interval (CI) 2.8, 15.1; P = 0.000 and OR: 2.7; 95% CI 1.9-3.9; P = 0.000). The combination of risk-factors is seen in 10% of the hearing-impaired group, whereas only 0.5% had it in the control group. Conclusion: Family history and consanguinity seems to be an important risk factor of hearing impairment both in isolation and in combination.

Primary Care Physician Management, Referral, and Relations with Specialists Concerning Patients at Risk for Cancer due to Family History

Background: Risk stratification based on family history is a feature of screening guidelines for a number of cancers and referral guidelines for genetic counseling/testing for cancer risk. Aims: Our aim was to describe primary care physician perceptions of their role in managing cancer risk based on family history. Methods: Structured interviews were conducted by a medical anthropologist with primary care physicians in 3 settings in 2 north-eastern states. Transcripts were systematically analyzed by a research team to identify major themes expressed by participants. Results: Forty interviews were conducted from May 2003 through May 2006. Physicians provided a diversity of views on roles in management of cancer risk based on family history, management practices and patient responses to risk information. They also provided a wide range of perspectives on criteria used for referral to specialists, types of specialists referred to and expected management roles for referred patients. Conclusion: Some primary care physicians appeared to make effective use of family history information for cancer risk management, but many in this sample did not. Increased focus on efficient assessment tools based on recognized guidelines, accessible guides to management options, and patient education and decision aids may be useful directions to facilitate broader use of family history information for cancer risk management.

Risk prediction for complex diseases: application to Parkinson disease.

The aim of this study was to evaluate the risk of Parkinson disease using clinical and demographic data alone and when combined with information from genes associated with Parkinson disease. A total of 1,967 participants in the dbGAP NeuroGenetics Research Consortium data set were included. Single-nucleotide polymorphisms associated with Parkinson disease at a genome-wide significance level in previous genome-wide association studies were included in risk prediction. Risk allele scores were calculated as the weighted count of the minor alleles. Five models were constructed. Discriminatory capability was evaluated using the area under the curve. Both family history and genetic risk scores increased risk for Parkinson disease. Although the fullest model, which included both family history and genetic risk information, resulted in the highest area under the curve, there were no significant differences between models using family history alone and those using genetic information alone. Adding genome-wide association study-derived genotypes, family history information, or both to standard demographic risk factors for Parkinson disease resulted in an improvement in discriminatory capacity. In the full model, the contributions of genotype data and family history information to discriminatory capacity were similar, and both were statistically significant. This suggests that there is limited overlap between genetic risk factors identified through genome-wide association study and unmeasured susceptibility variants captured by family history. Our results are similar to those of studies of other complex diseases and indicate that genetic risk prediction for Parkinson disease requires identification of additional genetic risk factors and/or better methods for risk prediction in order to achieve a degree of risk prediction that is clinically useful.Genet Med 2013:15(5):361-367.

Abstract 28: Characterization of SNPs associated with prostate cancer in men of Ashkenazic descent from the set of GWAS identified SNPs: Impact of cancer family history.

Abstract Background: Genome-wide association studies (GWAS) have identified several SNPs that are independently associated with prostate cancer (PrCa) in Caucasian men. Population isolates with unique allele frequencies are likely to have different sets of risk alleles for PrCa constituting personalized population risk stratification in addition to individual risk profiles. Methods: To test this hypothesis, we examined associations between 31 GWAS SNPs and PrCa among 979 cases and 1,251 controls of Ashkenazic descent. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated for each SNP using logistic regression models adjusted for age. We also investigated risk in strata by age at diagnosis, pathological features of PrCa, as well as family history of PrCa and other cancers. Results: Of 31 SNPs, 19 (62%) were associated with PrCa at p&amp;lt;0.05 in one or more genetic risk models. The strongest associations with PrCa were for rs6983267 at 8q24 (OR=1.78, p=5.7 x 10−7;comparison of GG vs. TT genotype), and rs1465618 at 2p21 (OR=2.19; p=0.003; AA vs. AG/GG). Six SNPs were associated with aggressive PrCa, while six others with less aggressive cancer. Four SNPs showed statistically significant interactions between PrCa and family history of PrCa (rs8102476 at 19q13), lung cancer (rs17021918 at 4q22), colorectal cancer (rs6983267 at 8q24), and breast cancer (rs10896449 at 11q13). Conclusion: These data define a specific set of risk alleles associated with PrCa in Ashkenazic men. Results demonstrate differences between men of European and Ashkenazic ancestry in relation to genetic susceptibility of PrCa. Interactions of genetic variants with family history of specific cancers indicate a complex network of inherited cancer risk syndromes still to be defined. Use of genetic markers to identify men at higher risk of PrCa will provide an opportunity for personalized care of PrCa prevention through screening of high-risk individuals, independent of family history information. Citation Format: Ilir Agalliu, Zhaoming Wang, Anne Dunn, Hemang Parikh, Timothy Myers, Robert Burk, Laufey Amundadottir. Characterization of SNPs associated with prostate cancer in men of Ashkenazic descent from the set of GWAS identified SNPs: Impact of cancer family history. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 28.