Dataset Information

The Relationship Between Population Attributable Fraction and Heritability in Genetic Studies.

ABSTRACT: Population attributable fraction (PAF) has been widely used to quantify the proportion of disease risk in a population that can be attributed to risk factors in epidemiological studies. However, the use of PAF has been limited in assessing the contribution of genetic variants. Most notably, the PAF estimate is typically much larger than other commonly used measures, such as heritability, thereby raising the concern that PAF may overestimate the genetic contribution. In this paper, we show that PAF is a one-to-one function of heritability, and explain why PAF is larger than heritability. Further, we present an estimation procedure based on the summary statistics from genome-wide association studies (GWAS) to estimate the PAF of multiple correlated genetic variants for a binary outcome. Currently available estimation procedures only apply to a single variant or to multiple genetic variants that are independent from each other. Our simulation studies verified the relationship between PAF and heritability, and showed that the proposed estimation procedure for these two measures performed well. Finally, we applied the proposed method to the published data of two lung cancer GWAS to estimate the PAF and heritability of several newly identified variants. Our results demonstrate that the PAF estimate is a useful measure of the genetic contribution to the development of the disease. We hope this paper serves as an advocate for a wider use of PAF in genetic studies.

SUBMITTER: Wang T

PROVIDER: S-EPMC6174220 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The Relationship Between Population Attributable Fraction and Heritability in Genetic Studies.

Wang Tao T Hosgood H Dean HD Lan Qing Q Xue Xiaonan X

Frontiers in genetics 20181001

Population attributable fraction (PAF) has been widely used to quantify the proportion of disease risk in a population that can be attributed to risk factors in epidemiological studies. However, the use of PAF has been limited in assessing the contribution of genetic variants. Most notably, the PAF estimate is typically much larger than other commonly used measures, such as heritability, thereby raising the concern that PAF may overestimate the genetic contribution. In this paper, we show that P ...[more]

PMID: 30327663

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Project description:Chlamydia trachomatis infection is highly prevalent among young women in the United States. Prevention of long-term sequelae of infection, including tubal factor infertility, is a primary goal of chlamydia screening and treatment activities. However, the population-attributable fraction of tubal factor infertility associated with chlamydia is unclear, and optimal measures for assessing tubal factor infertility and prior chlamydia in epidemiological studies have not been established. Black women have increased rates of chlamydia and tubal factor infertility compared with White women but have been underrepresented in prior studies of the association of chlamydia and tubal factor infertility.The objectives of the study were to estimate the population-attributable fraction of tubal factor infertility associated with Chlamydia trachomatis infection by race (Black, non-Black) and assess how different definitions of Chlamydia trachomatis seropositivity and tubal factor infertility affect population-attributable fraction estimates.We conducted a case-control study, enrolling infertile women attending infertility practices in Birmingham, AL, and Pittsburgh, PA, during October 2012 through June 2015. Tubal factor infertility case status was primarily defined by unilateral or bilateral fallopian tube occlusion (cases) or bilateral fallopian tube patency (controls) on hysterosalpingogram. Alternate tubal factor infertility definitions incorporated history suggestive of tubal damage or were based on laparoscopic evidence of tubal damage. We aimed to enroll all eligible women, with an expected ratio of 1 and 3 controls per case for Black and non-Black women, respectively. We assessed Chlamydia trachomatis seropositivity with a commercial assay and a more sensitive research assay; our primary measure of seropositivity was defined as positivity on either assay. We estimated Chlamydia trachomatis seropositivity and calculated Chlamydia trachomatis-tubal factor infertility odds ratios and population-attributable fraction, stratified by race.We enrolled 107 Black women (47 cases, 60 controls) and 620 non-Black women (140 cases, 480 controls). Chlamydia trachomatis seropositivity by either assay was 81% (95% confidence interval, 73-89%) among Black and 31% (95% confidence interval, 28-35%) among non-Black participants (P < .001). Using the primary Chlamydia trachomatis seropositivity and tubal factor infertility definitions, no significant association was detected between chlamydia and tubal factor infertility among Blacks (odds ratio, 1.22, 95% confidence interval, 0.45-3.28) or non-Blacks (odds ratio, 1.41, 95% confidence interval, 0.95-2.09), and the estimated population-attributable fraction was 15% (95% confidence interval, -97% to 68%) among Blacks and 11% (95% confidence interval, -3% to 23%) among non-Blacks. Use of alternate serological measures and tubal factor infertility definitions had an impact on the magnitude of the chlamydia-tubal factor infertility association and resulted in a significant association among non-Blacks.Low population-attributable fraction estimates suggest factors in addition to chlamydia contribute to tubal factor infertility in the study population. However, high background Chlamydia trachomatis seropositivity among controls, most striking among Black participants, could have obscured an association with tubal factor infertility and resulted in a population-attributable fraction that underestimates the true etiological role of chlamydia. Choice of chlamydia and tubal factor infertility definitions also has an impact on the odds ratio and population-attributable fraction estimates.

Project description:BackgroundSevere maternal morbidity is an important proxy for maternal mortality. Population attributable fraction is the proportion of a disease that is attributable to a given risk factor and can be used to estimate the reduction in the disease that would be anticipated if a risk factor was reduced or eliminated.ObjectiveWe sought to determine the population-attributable fraction (PAF) of potentially modifiable risk factors for severe maternal morbidity.Study designWe used a retrospective cohort of 86,260 delivery hospitalizations from Magee-Womens Hospital, Pittsburgh, PA for this analysis (2003-2012). Severe maternal morbidity was defined as any of the following: Centers for Disease Control and Prevention International Classification of Diseases 9th Revision diagnosis and procedure codes for the identification of maternal morbidity; prolonged postpartum length of stay (defined as >3 standard deviations beyond the mean length of stay: >3 days for vaginal deliveries and >5 days for Cesarean deliveries); or maternal intensive care unit admission. We used multivariable logistic regression with generalized estimating equations to estimate the association of prepregnancy overweight or obesity, maternal age ≥35 years, preexisting hypertension, preexisting diabetes, excessive gestational weight gain, smoking, education, and marital status with severe maternal morbidity. We then calculated the PAF for each risk factor. We also examined the impact of modest reductions and elimination of risk factors on the PAF of severe maternal morbidity.ResultsThe overall rate of severe maternal morbidity was 2.0%. Overweight and obesity, maternal age ≥35 years, preexisting hypertension, excessive gestational weight gain, and lack of a college degree had PAF ranging from 4.5% to 13%. If all risk factors were eliminated, 36% of cases could have been prevented. Modest reductions in the prevalence of excessive BMI and advanced maternal age had minimal impact on preventing severe maternal morbidity. Smoking during pregnancy and marital status were not associated with severe maternal morbidity.ConclusionsOur data suggest maternal morbidity can be reduced by modifying common, individual-level risk factors. Nevertheless, the majority of cases were not attributable to the patient level risk factors we examined. These data support the need for large studies of patient-, provider-, system- and population-level factors to identify high-impact interventions to reduce maternal morbidity.

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The Relationship Between Population Attributable Fraction and Heritability in Genetic Studies.

Publications

The Relationship Between Population Attributable Fraction and Heritability in Genetic Studies.

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