Case–control association mapping by proxy using family history of disease

AbstractFamily history of disease can provide valuable information about an individual’s genetic liability for disease in case-control association studies, but it is currently unclear how to best combine case-control status and family history of disease. We developed a new association method based on posterior mean genetic liabilities under a liability threshold model, conditional on both case-control status and family history (LT-FH); association statistics are computed via linear regression of genotypes and posterior mean genetic liabilities, equivalent to a score test. We applied LT-FH to 12 diseases from the UK Biobank (average N=350K). We compared LT-FH to genome-wide association without using family history (GWAS) and a previous proxy-based method for incorporating family history (GWAX). LT-FH was +63% (s.e. 6%) more powerful than GWAS and +36% (s.e. 4%) more powerful than the trait-specific maximum of GWAS and GWAX, based on the number of independent genome-wide significant loci detected across all diseases (e.g. 690 independent loci for LT-FH vs. 423 for GWAS); the second best method was GWAX for lower-prevalence diseases and GWAS for higher-prevalence diseases, consistent with simulations. We also confirmed that LT-FH was well-calibrated (assessed via stratified LD score regression attenuation ratio), consistent with simulations. When using BOLT-LMM (instead of linear regression) to compute association statistics for all three methods (increasing the power of each method), LT-FH was +67% (s.e. 6%) more powerful than GWAS and +39% (s.e. 4%) more powerful than the trait-specific maximum of GWAS and GWAX. In summary, LT-FH greatly increases association power in case-control association studies when family history of disease is available.

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Liability threshold modeling of case–control status and family history of disease increases association power

Nature Genetics ◽

10.1038/s41588-020-0613-6 ◽

2020 ◽

Vol 52 (5) ◽

pp. 541-547 ◽

Cited By ~ 3

Author(s):

Margaux L. A. Hujoel ◽

Steven Gazal ◽

Po-Ru Loh ◽

Nick Patterson ◽

Alkes L. Price

Keyword(s):

Family History ◽

Case Control ◽

History Of Disease ◽

History Of ◽

Threshold Modeling

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The association between diabetes and thyroid cancer risk: a hospital-based case-control study in China

BMC Endocrine Disorders ◽

10.1186/s12902-021-00684-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Meng Wang ◽

Wei-Wei Gong ◽

Feng Lu ◽

Ru-Ying Hu ◽

Qing-Fang He ◽

...

Keyword(s):

Thyroid Cancer ◽

Family History ◽

Case Control Study ◽

Positive Family History ◽

Case Control ◽

Diabetes Duration ◽

Family History Of Diabetes ◽

Thyroid Cancer Risk ◽

History Of ◽

Control Study

Abstract Background Previous studies have indicated inconsistent relationships of diabetes with thyroid cancer risk, yet little is known in China. In this study, we aimed to investigate the associations between diabetes, diabetes duration and the risk of thyroid cancer in Chinese population. Methods A 1:1 matched case-control study was performed between 2015 and 2017 in Zhejiang Province including 2,937 thyroid cancer cases and 2,937 healthy controls. Odds ratios (ORs) with 95 % confidence intervals (CIs) for thyroid cancer were estimated in logistic regression models. Specific effects stratified by age, as well as sex, body mass index (BMI) and family history of diabetes were also examined. Results Overall, neither diabetes (OR = 0.75, 95 % CI: 0.21–2.73) nor diabetes duration (OR = 0.14, 95 % CI: 0.02–1.22 for diabetes duration ≦ 5 years; OR = 2.10, 95 % CI: 0.32–13.94 for diabetes duration > 5 years) was significantly associated with thyroid cancer. In stratified analyses, significant lower risk of thyroid cancer was observed among subjects with diabetes and shorter diabetes duration ( ≦ 5 years), but limited to those who were aged more than 40 years, female, overweight/obese and had positive family history of diabetes. Conclusions Diabetes and shorter diabetes duration were significantly associated with decreased risk of thyroid cancer in individuals characterized by older age, female sex, higher BMI and positive family history of diabetes.

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Leveraging Family History in Population-Based Case-Control Association Studies

Genetic Epidemiology ◽

10.1002/gepi.21785 ◽

2014 ◽

Vol 38 (2) ◽

pp. 114-122 ◽

Cited By ~ 1

Author(s):

Arpita Ghosh ◽

Patricia Hartge ◽

Peter Kraft ◽

Amit D. Joshi ◽

Regina G. Ziegler ◽

...

Keyword(s):

Family History ◽

Association Studies ◽

Population Based ◽

Case Control ◽

Control Association

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Family history of hypertension increases risk of preeclampsia in pregnant women: a case-control study

Zinc supplementation improves heme biosynthesis in rats exposed to lead ◽

10.18051/univmed.2016.v35.181-191 ◽

2016 ◽

Vol 35 (3) ◽

pp. 181 ◽

Cited By ~ 1

Author(s):

Mulualem Endeshaw ◽

Fantu Abebe ◽

Melkamu Bedimo ◽

Anemaw Asrat ◽

Abebaw Gebeyehu ◽

...

Keyword(s):

Family History ◽

Pregnant Women ◽

Case Control Study ◽

Multiple Logistic Regression Analysis ◽

Multiple Pregnancy ◽

Case Control ◽

Outcome Variable ◽

History Of ◽

Family History Of Hypertension ◽

Control Study

Background Preeclampsia is one of the leading causes of maternal and fetal morbidity and mortalities worldwide. Despite extensive research, the underlying cause of preeclampsia remains poorly understood. This study aimed to offer compelling evidence on the important risk factors of preeclampsia in Amhara region, Ethiopia. Methods A case control study was conducted in public health facilities of Bahir Dar city from September 2014 to January 2015. A total of 453 (151 cases and 302 controls) pregnant women were enrolled in this study. Hemoglobin level and urinary tract infection (UTI) status were collected from clinical notes. Oral examination was performed by a dentist for detection of periodontal diseases. Univariate and multiple logistic regression analysis was conducted to determine the relationship of all the independent variables with the outcome variable. A p-value <0.05 was declared statistically significant. Result Advanced maternal age (AOR=4.79;95% CI 1.031-22.18), family history of hypertension (AOR=11.16;95% CI 5.41-41.43), history of diabetes mellitus (AOR=6.17;95% CI 2.11-20.33), UTI in the current pregnancy (AOR=6.58;95% CI 2.93-14.73), failure to comply with iron and folic acid supplement during pregnancy (AOR=8.32;95% CI 3.35-20.62), lack of exercise (AOR=3.33;95% CI 1.35-8.17), multiple pregnancy (AOR=4.05;95% CI 1.57-12.27), anemia (AOR=4.19;95% CI 1.27-13.92), and periodontal disease or gingivitis (AOR =3.51;95% CI 1.14-10.83) were associated with preeclampsia. Conclusion Family history of hypertension was the most dominant risk factor for preeclampsia in pregnant women. Encouraging pregnant women to have health seeking behavior during pregnancy would provide a chance to diagnose preeclampsia as early as possible.

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Risk of Dysglycemia in Pregnancy amongst Kenyan Women with HIV Infection: A Nested Case-Control Analysis from the STRiDE Study

Journal of Diabetes Research ◽

10.1155/2021/8830048 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Sonak D. Pastakia ◽

Wycliffe K. Kosgei ◽

Astrid Christoffersen-Deb ◽

Benson Kiragu ◽

John N. Hector ◽

...

Keyword(s):

Family History ◽

Pregnant Women ◽

Gestational Age ◽

Fasting Glucose ◽

Case Control ◽

Oral Glucose ◽

Control Analysis ◽

History Of ◽

Women With Hiv ◽

Nested Case Control

Introduction. Gestational diabetes is a common complication, whose incidence is growing globally. There is a pressing need to obtain more data on GDM in low- and middle-income countries, especially amongst high-risk populations, as most of the data on GDM comes from high-income countries. With the growing awareness of the role HIV plays in the progression of noncommunicable diseases and the disproportionate HIV burden African countries like Kenya face, investigating the potential role HIV plays in increasing dysglycemia amongst pregnant women with HIV is an important area of study. Methods. The STRiDE study is one of the largest ever conducted studies of GDM in Kenya. This study enrolled pregnant women aged between 16 and 50 who were receiving care from public and private sector facilities in Eldoret, Kenya. Within this study, women received venous testing for glycosylated hemoglobin (HbA1c) and fasting glucose between 8- and 20-week gestational age. At their 24-32-week visit, they received a venous 75 g oral glucose tolerance test (OGTT). Because of the pressing need to assess the burden of GDM within the population of pregnant women with HIV, a nested case-control study design was used. Pregnant women with HIV within the larger STRiDE cohort were matched to non-HIV-infected women within the STRiDE cohort at a 1 : 3 ratio based on body mass index, parity, family history of GDM, gestational age, and family history of hypertension. The measurements of glucose from the initial visit (fasting glucose and HbA1c) and follow-up visit (OGTT) were compared between the two groups of HIV+ cases and matched HIV- controls. Results. A total of 83 pregnant women with HIV were well matched to 249 non-HIV-infected women from the STRiDE cohort with marital status being the only characteristic that was statistically significantly different between the two groups. Statistically significant differences were not observed in the proportion of women who developed GDM, the fasting glucose values, the HbA1c, or OGTT measurements between the two groups. Discussion. Significant associations were not seen between the different measures of glycemic status between pregnant women with and without HIV. While significant differences were not seen in this cohort, additional investigation is needed to better describe the association of dysglycemia with HIV, especially in Kenyan populations with a higher prevalence of GDM.

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Analysis of pulmonary features and treatment approaches in the COPA syndrome

ERJ Open Research ◽

10.1183/23120541.00017-2018 ◽

2018 ◽

Vol 4 (2) ◽

pp. 00017-2018 ◽

Cited By ~ 32

Author(s):

Jessica L. Tsui ◽

Oscar A. Estrada ◽

Zimu Deng ◽

Kristin M. Wang ◽

Christopher S. Law ◽

...

Keyword(s):

Family History ◽

Lung Disease ◽

Alveolar Haemorrhage ◽

Diffuse Alveolar Haemorrhage ◽

Diffuse Parenchymal Lung Disease ◽

History Of Disease ◽

History Of ◽

Parenchymal Lung Disease ◽

Copa Syndrome ◽

Parenchymal Lung

The COPA syndrome is a monogenic, autoimmune lung and joint disorder first identified in 2015. This study sought to define the main pulmonary features of the COPA syndrome in an international cohort of patients, analyse patient responses to treatment and highlight when genetic testing should be considered.We established a cohort of subjects (N=14) with COPA syndrome seen at multiple centres including the University of California, San Francisco, CA, USA. All subjects had one of the previously established mutations in the COPA gene, and had clinically apparent lung disease and arthritis. We analysed cohort characteristics using descriptive statistics.All subjects manifested symptoms before the age of 12 years, had a family history of disease, and developed diffuse parenchymal lung disease and arthritis. 50% had diffuse alveolar haemorrhage. The most common pulmonary findings included cysts on chest computed tomography and evidence of follicular bronchiolitis on lung biopsy. All subjects were positive for anti-neutrophil cytoplasmic antibody, anti-nuclear antibody or both and 71% of subjects had rheumatoid factor positivity. All subjects received immunosuppressive therapy.COPA syndrome is an autoimmune disorder defined by diffuse parenchymal lung disease and arthritis. We analysed an international cohort of subjects with genetically confirmed COPA syndrome and found that common pulmonary features included cysts, follicular bronchiolitis and diffuse alveolar haemorrhage. Common extrapulmonary features included early age of onset, family history of disease, autoantibody positivity and arthritis. Longitudinal data demonstrated improvement on chest radiology but an overall decline in pulmonary function despite chronic treatment.

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