Polycystic Ovary Syndrome
Introduction
Section titled “Introduction”Background
Section titled “Background”Polycystic Ovary Syndrome (PCOS) is a common, complex endocrine disorder affecting women of reproductive age worldwide. It is characterized by a combination of hormonal imbalances, metabolic dysfunction, and often the presence of multiple small, fluid-filled sacs (cysts) on the ovaries. The underlying causes of PCOS are not fully understood, but it is believed to result from a multifaceted interplay of genetic predispositions and environmental factors.
Biological Basis
Section titled “Biological Basis”The biological underpinnings of PCOS involve a complex interplay of hormonal dysregulation, including insulin resistance, hyperandrogenism (elevated levels of male hormones like testosterone), and ovulatory dysfunction. Insulin resistance, a key feature in many individuals with PCOS, leads to higher circulating insulin levels, which can stimulate the ovaries to produce excess androgens. These elevated androgen levels contribute to many of the clinical symptoms.
PCOS is recognized as a complex genetic disorder with a polygenic nature, meaning multiple genes and genetic variants contribute to an individual’s susceptibility. Research into the genetic architecture of PCOS often employs genome-wide association studies (GWAS) to identify common genetic variants, such as Single Nucleotide Polymorphisms (SNPs), that are associated with the condition. These studies typically involve a rigorous quality control process for SNPs, which includes filtering out variants with low call rates, significant deviations from Hardy-Weinberg equilibrium in control groups, or minor allele frequencies (MAF) below a certain threshold.[1] Statistical analyses, such as logistic regression, are then performed to test for associations between SNPs and the trait, often adjusting for potential population stratification using principal components analysis.[1] Different genetic models, including additive, dominant, and recessive, may be evaluated to determine the most significant mode of inheritance.[1] Furthermore, meta-analyses are frequently conducted to combine results from multiple independent studies, enhancing statistical power and the ability to identify robust genetic associations.[2]
Clinical Relevance
Section titled “Clinical Relevance”PCOS presents a diverse range of clinical manifestations, impacting various aspects of women’s health. Key reproductive issues include irregular menstrual cycles, anovulation (lack of ovulation), and infertility. Androgenic symptoms, resulting from excess male hormones, can manifest as hirsutism (excess body hair), acne, and androgenic alopecia (pattern hair loss). Beyond reproductive and cosmetic concerns, PCOS is significantly associated with metabolic health issues, such as insulin resistance, an increased risk of developing type 2 diabetes, obesity, and dyslipidemia. These metabolic disturbances can also contribute to an elevated risk of cardiovascular disease. Early diagnosis and comprehensive management are essential to mitigate these diverse symptoms and prevent long-term health complications associated with the syndrome.
Social Importance
Section titled “Social Importance”PCOS affects a substantial proportion of women globally, making it a significant public health challenge. Its chronic nature and broad spectrum of symptoms can profoundly impact an individual’s quality of life, body image, and mental well-being, often leading to increased rates of anxiety and depression. The condition’s prevalence and its wide-ranging health implications underscore the critical need for increased public awareness, improved diagnostic protocols, and effective treatment strategies. Enhanced understanding and support for individuals with PCOS are vital to address both the physical and psychosocial burdens of the syndrome.
Methodological and Statistical Constraints
Section titled “Methodological and Statistical Constraints”Genetic studies of complex traits like polycystic ovary syndrome (PCOS) face inherent methodological and statistical challenges. While large-scale genome-wide association studies (GWAS) increase statistical power, they can also introduce heterogeneity, especially when combining diverse cohorts. A significant concern is the potential for effect-size inflation in initial discoveries, which can contribute to replication failures, particularly for variants with low allele frequencies or modest effects.[3] Furthermore, the stringent statistical thresholds required to address the massive multiple testing burden in GWAS may lead to overlooking genuine genetic associations with subtle effects that do not reach genome-wide significance.
The comprehensive capture of genetic variation remains a challenge, as standard GWAS primarily focus on common single nucleotide polymorphisms (SNPs) and may miss the contributions of rare variants, structural variants, or those not adequately represented in imputation reference panels.[4] Additionally, methods like Mendelian Randomization, while powerful for inferring causality, are susceptible to biases from horizontal pleiotropy, where a genetic variant affects multiple traits independently of the exposure of interest, or from weak genetic instruments.[5] These factors can complicate the accurate estimation of genetic effects and the identification of true causal pathways in PCOS.
Phenotypic Heterogeneity and Population Generalizability
Section titled “Phenotypic Heterogeneity and Population Generalizability”The definition and ascertainment of complex conditions such as PCOS introduce significant phenotypic heterogeneity across studies. Different diagnostic criteria (e.g., varying thresholds for oligo-anovulation, hyperandrogenism, or polycystic ovarian morphology) can lead to varied case definitions, potentially diluting genetic signals and making cross-study comparisons difficult. While some research indicates that different ascertainment methods, such as clinician diagnosis versus research-based assessment, may yield similar patterns of effect sizes for associated loci, the underlying phenotypic diversity remains a critical consideration.[6] This is particularly relevant for PCOS, a female-specific condition, where the omission of sex-specific genetic analyses in broader studies could result in undetected associations unique to females.[4] A major limitation in the generalizability of genetic findings is the historical overrepresentation of individuals of European ancestry in large-scale GWAS.[7] This demographic imbalance restricts the applicability of identified genetic risk factors to other populations, as allele frequencies, linkage disequilibrium patterns, and the overall genetic architecture of diseases can vary substantially across different ancestries. Consequently, the current understanding of PCOS genetics may be incomplete for diverse global populations, contributing to potential disparities in genetic risk prediction and therapeutic strategies.
Incomplete Etiological Understanding
Section titled “Incomplete Etiological Understanding”Despite the advancements in identifying genetic loci associated with PCOS, a substantial portion of its heritability remains unexplained, a phenomenon known as “missing heritability.” This gap suggests that standard GWAS, which primarily focus on common variants, may not fully account for the genetic complexity, including the roles of rare variants, structural variants, gene-gene interactions, or epigenetic modifications.[4] A comprehensive understanding of PCOS etiology is further complicated by the intricate interplay between genetic predispositions and environmental factors.
Environmental influences, such as diet, lifestyle, and exposure to endocrine disruptors, are known to contribute significantly to the development and severity of PCOS, yet these gene-environment interactions are challenging to systematically measure and model in large genetic studies. Unaccounted environmental confounders can obscure true genetic effects or lead to spurious associations, making it difficult to disentangle genetic risk from environmental exposures. Moreover, the widespread phenomenon of horizontal pleiotropy, where single genetic variants can influence multiple seemingly unrelated traits, adds complexity to interpreting causal relationships and fully elucidating the biological mechanisms underlying PCOS.[5] Addressing these gaps requires integrative approaches that combine detailed genetic, environmental, and phenotypic data.
Variants
Section titled “Variants”Genetic variations, or single nucleotide polymorphisms (SNPs), contribute to an individual’s susceptibility to complex conditions like Polycystic Ovary Syndrome (PCOS) by influencing gene function and biological pathways. Genome-wide association studies (GWAS) are instrumental in identifying such genetic loci, although their associations can vary across different traits and populations.[8] For instance, variants in the FTO gene, including rs8050136 , rs9930501 , and rs8047587 , are well-known for their strong association with obesity and metabolic traits. Given that obesity and insulin resistance are common features of PCOS, theseFTOvariants can exacerbate the metabolic dysfunction seen in affected individuals by influencing appetite regulation and energy expenditure. TheRAB5B-SUOX intergenic region, represented by rs705702 , may also play a role in metabolic regulation, potentially affecting cellular transport or sulfur metabolism, which can indirectly contribute to the complex endocrine environment of PCOS. Furthermore, the GIPR gene, with its variant rs2238689 , encodes the receptor for glucose-dependent insulinotropic polypeptide, a hormone vital for insulin secretion; variations here can impact glucose homeostasis and insulin sensitivity, key aspects of PCOS pathophysiology.[9] Another set of critical variants associated with PCOS are found in the DENND1A gene, including rs7030193 , rs2479106 , and rs3945628 . DENND1A is involved in endocytosis and has been identified as a significant genetic risk factor for PCOS, particularly influencing ovarian androgen production, a hallmark of the syndrome. These variants are believed to alter DENND1A expression or function, leading to increased androgen synthesis in ovarian cells and contributing to hyperandrogenism, a primary diagnostic criterion for PCOS.[8] Similarly, the THADA gene, with variants like rs13429458 and rs12478601 , has been implicated in PCOS susceptibility. While its exact mechanism in PCOS is still under investigation, THADA is thought to influence cell proliferation and growth, potentially affecting ovarian follicular development and contributing to the characteristic polycystic morphology of the ovaries.[9] Further genetic insights into PCOS involve genes like YAP1, HMGA2, CHEK2, and the STON1-GTF2A1L, LHCGR locus. Variants in YAP1, such as rs1894116 , rs11225154 , and rs111520626 , are associated with the Hippo signaling pathway, which is crucial for organ size control and cell proliferation; dysregulation in this pathway could impact ovarian development and folliculogenesis in PCOS. TheHMGA2 gene, represented by rs2272046 , is known for its role in growth and development, and has been linked to various metabolic parameters and body fat distribution, which are often disturbed in women with PCOS.[8] Moreover, CHEK2 variants (rs17879961 , rs182075939 ) encode a kinase involved in cell cycle arrest and DNA repair. While less directly associated with reproductive hormones, alterations in cell cycle control could affect ovarian cell health and function. Critically, the rs13405728 variant located within the STON1-GTF2A1L and LHCGR region points to the LHCGRgene (Luteinizing Hormone/Choriogonadotropin Receptor), which is indispensable for ovarian steroidogenesis and ovulation. Genetic variations here can impair the ovary’s response to LH, leading to anovulation and hyperandrogenism, central features of PCOS.[9]
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs8050136 rs9930501 rs8047587 | FTO | age at menarche type 2 diabetes mellitus body weight body mass index obesity |
| rs705702 | RAB5B - SUOX | polycystic ovary syndrome forced expiratory volume, gastroesophageal reflux disease eosinophil count Nasal Cavity Polyp level of neural cell adhesion molecule 1 in blood serum |
| rs2238689 | GIPR | polycystic ovary syndrome low density lipoprotein cholesterol , free cholesterol:total lipids ratio phospholipids:totallipids ratio, high density lipoprotein cholesterol body mass index type 2 diabetes mellitus |
| rs7030193 rs2479106 rs3945628 | DENND1A | polycystic ovary syndrome |
| rs13429458 | THADA | polycystic ovary syndrome response to xenobiotic stimulus |
| rs12478601 | THADA | polycystic ovary syndrome systolic blood pressure osteoclast-associated immunoglobulin-like receptor signal-regulatory protein beta-1 blood urea nitrogen amount |
| rs1894116 rs11225154 rs111520626 | YAP1 | polycystic ovary syndrome |
| rs2272046 | HMGA2 | polycystic ovary syndrome body height |
| rs17879961 rs182075939 | CHEK2 | breast carcinoma lung carcinoma squamous cell carcinoma upper aerodigestive tract neoplasm squamous cell lung carcinoma |
| rs13405728 | STON1-GTF2A1L, LHCGR | polycystic ovary syndrome |
Endocrine and Metabolic Profile
Section titled “Endocrine and Metabolic Profile”The comprehensive assessment of health phenotypes often includes a detailed evaluation of endocrine and metabolic markers. This involves objective measurements such as fasting blood glucose levels, triglycerides, HDL cholesterol, LDL cholesterol, total cholesterol, and hemoglobin A1c, all typically assessed through blood tests.[10]Additionally, specific hormonal markers like Thyroid-Stimulating Hormone are routinely measured, providing insight into endocrine function.[10] The presence of broader metabolic conditions, including metabolic syndrome, diagnosed diabetes, and diagnosed dyslipidemia, are also considered as significant indicators within this category, reflecting systemic metabolic health and potential underlying imbalances.[10] These biomarkers are crucial for understanding an individual’s endocrine landscape and its implications for various health outcomes.
Physical and Imaging Assessments
Section titled “Physical and Imaging Assessments”Clinical presentation also involves a range of physical and structural evaluations, combining both objective and subjective data. Anthropometric measures, such as those derived from body composition analyzers like the InBody® system, provide quantitative data on physical characteristics.[10] For internal organ assessment, abdominal ultrasonography is employed as a diagnostic tool to visualize anatomical structures.[10]Complementing these objective methods, subjective participant-reported phenotypic data is collected through questionnaire interviews, capturing symptoms and lifestyle factors that may not be apparent through physical examination alone.[10] This multi-modal approach helps in characterizing the diverse physical manifestations of various conditions.
Phenotypic Heterogeneity and Diagnostic Considerations
Section titled “Phenotypic Heterogeneity and Diagnostic Considerations”The presentation of clinical phenotypes is marked by significant inter-individual variation and heterogeneity, which necessitates careful consideration during assessment. Factors such as age and sex are frequently included as covariates in analyses to account for observed phenotypic diversity.[11] This variability means that individuals may present with a wide spectrum of symptom severity and patterns, making a comprehensive and nuanced diagnostic approach essential. The diagnostic significance of these phenotypes lies in their ability to inform differential diagnoses and identify “red flags” that may indicate specific health conditions. The “extreme phenotype approach,” for example, can be utilized to distinguish between mild and severe manifestations, thereby contributing to a better understanding of the condition’s full clinical spectrum and guiding prognostic indicators.[12]
Causes of Polycystic Ovary Syndrome
Section titled “Causes of Polycystic Ovary Syndrome”The etiology of polycystic ovary syndrome (PCOS) is multifactorial, arising from a complex interplay of genetic predispositions, environmental exposures, and developmental programming. While the precise mechanisms are still being elucidated, research into metabolic traits, which frequently overlap with the clinical presentation of PCOS, provides insights into these contributing factors. These investigations highlight how various influences converge to affect endocrine and reproductive health.
Genetic Predisposition and Gene-Environment Interactions
Section titled “Genetic Predisposition and Gene-Environment Interactions”Genetic factors are understood to contribute significantly to the susceptibility of developing complex conditions such as PCOS. While specific inherited variants for PCOS are a focus of ongoing research, studies analyze how an individual’s genotype, encompassing various genetic loci, interacts with their environment to influence metabolic traits relevant to the syndrome.[13] This includes evaluating interactions between genotype and variables like sex, the use of oral contraceptives, and an individual’s overweight status (defined as BMI > 25).[13] Such analyses aim to uncover how genetic predispositions are expressed or modified by external factors, contributing to the diverse phenotypes observed in PCOS.
The investigation of gene-environment interactions is crucial for a comprehensive understanding of complex endocrine disorders. Researchers examine how the effect size of specific genetic loci varies across different demographic and lifestyle groups, such as comparing effects in males versus females or in individuals using oral contraceptives.[13]Furthermore, the interplay between genotype and factors like overweight status, gestational age, birth BMI, and early growth is analyzed, often adjusting for other covariates to isolate the specific interactive effects.[13] These studies illustrate that genetic susceptibility to metabolic and reproductive dysregulation is not static but dynamically influenced by an individual’s surrounding environment and physiological state.
Early Life and Developmental Influences
Section titled “Early Life and Developmental Influences”Early life experiences and developmental factors play a critical role in programming an individual’s long-term metabolic and reproductive health, thereby influencing susceptibility to conditions like PCOS. Key early life covariates, such as gestational age (whether birth was pre-term or full-term), birth BMI, and patterns of early growth, are recognized as significant variables for understanding an individual’s risk profile.[13]These factors can impact developmental trajectories and metabolic programming, which may predispose individuals to the endocrine imbalances characteristic of PCOS later in life. Although specific details on epigenetic modifications like DNA methylation or histone modifications are not always explicitly defined in all studies, the focus on these early life variables underscores the importance of developmental origins.
The influence of these developmental factors is often intertwined with an individual’s genetic makeup, demonstrating complex gene-environment interactions from an early age. For instance, the impact of specific genotypes on metabolic outcomes can be modulated by an individual’s conditions at birth or their growth patterns during infancy.[13] A thorough understanding of how these early developmental signals interact with genetic predispositions is essential for deciphering the intricate origins and heterogeneity of complex conditions affecting reproductive and metabolic systems.
Lifestyle and Exogenous Factors
Section titled “Lifestyle and Exogenous Factors”Beyond inherent genetic and early developmental influences, various lifestyle and exogenous factors contribute significantly to the risk and manifestation of metabolic and endocrine conditions, including PCOS. An individual’s overweight status, characterized by a Body Mass Index (BMI) greater than 25, is a prominent epidemiological covariate frequently investigated for its interaction with genetic factors.[13]This suggests that dietary habits, physical activity levels, and other lifestyle choices contributing to body composition can modulate genetic predispositions, influencing the development and severity of metabolic dysregulation relevant to PCOS.
Furthermore, the use of specific exogenous agents, such as oral contraceptives, is also considered a critical factor in the analysis of metabolic traits.[13] Research examines how the effects of an individual’s genotype can vary depending on their use of oral contraceptives, indicating that hormonal influences or pharmacological interventions can modify the expression of genetic susceptibilities.[13]These lifestyle and exogenous elements do not act in isolation but rather engage in dynamic interactions with an individual’s genetic background and developmental history, collectively shaping the overall risk and clinical presentation of complex disorders.
Biological Background of Polycystic Ovary Syndrome
Section titled “Biological Background of Polycystic Ovary Syndrome”Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder affecting individuals with ovaries, characterized by a spectrum of reproductive and metabolic abnormalities. The underlying biology involves intricate dysregulation of hormonal pathways, genetic predispositions, and systemic metabolic disturbances that collectively contribute to its diverse manifestations.
Hormonal Dysregulation and Reproductive System Disruption
Section titled “Hormonal Dysregulation and Reproductive System Disruption”PCOS is fundamentally linked to imbalances in sex steroid hormones and their impact on reproductive organs. Estrogen receptor signaling plays a crucial role in the development and function of the reproductive system, influencing cell growth and differentiation in tissues like the uterus. For instance, the mitotic rates of endometrial tissue are significantly higher during the follicular phase of the menstrual cycle when estrogen levels are elevated and progesterone is low, leading to endometrial proliferation.[14] This imbalance, often seen in conditions associated with PCOS, can lead to hyperplasia, which can be reversed by progestin therapy.[14]Furthermore, ovarian function is critically dependent on gonadotropins, such as follicle-stimulating hormone (FSH), which accelerates oocyte development; mutations in theFSHBgene, encoding the beta-subunit of FSH, can lead to hypogonadism and delayed puberty.[15] This highlights the delicate hormonal control over ovarian processes, which can be disrupted in PCOS.
Genetic Underpinnings and Gene Regulation
Section titled “Genetic Underpinnings and Gene Regulation”The predisposition to PCOS and related gynecologic conditions involves a complex interplay of genetic mechanisms and regulatory elements. Genome-wide association studies (GWAS) have identified common genetic origins across various gynecologic diseases, suggesting shared susceptibility pathways.[16] For example, the CYP19A1gene, which encodes aromatase, an enzyme crucial for estrogen synthesis, contains polymorphic variants that may be associated with the risk of endometrial cancer, a condition often co-occurring with PCOS.[14]Beyond estrogen metabolism, genes likeGREB1are identified as androgen-regulated and are required for certain cancer growths, indicating a link between androgen signaling and cellular proliferation in hormone-sensitive tissues.[15]Other genetic factors, such as polymorphisms in vitamin D-related genes, have also been investigated in the context of uterine leiomyomata, suggesting broader genetic influences on reproductive health.[17] Moreover, the FOXO3gene, a transcription factor involved in cell fate decisions, has shown deregulation in uterine smooth muscle tumors, indicating its role in tissue development and disease pathogenesis within the reproductive system.[17]
Metabolic and Systemic Factors in Disease Pathogenesis
Section titled “Metabolic and Systemic Factors in Disease Pathogenesis”PCOS is frequently associated with metabolic disturbances that extend beyond the reproductive system, impacting overall systemic health. Obesity, a common comorbidity, has been identified as a causal risk factor for uterine endometrial cancer.[18]This connection underscores the role of metabolic processes in influencing hormone-sensitive cancers, linking systemic metabolic health to gynecologic disease risk. Hypertension has also been studied in relation to uterine leiomyomata, suggesting broader cardiovascular and metabolic influences on reproductive organ health.[18]These systemic disruptions, including alterations in fat metabolism and insulin signaling, contribute to a pro-inflammatory and hyperandrogenic environment that exacerbates the features of PCOS and increases the risk for associated conditions.
Cellular Proliferation and Tissue Development
Section titled “Cellular Proliferation and Tissue Development”At the cellular and tissue level, PCOS involves aberrant proliferation and differentiation processes within reproductive organs, particularly the ovaries and endometrium. The cellular functions of the endometrium are tightly regulated by steroid hormones, with progesterone counteracting the growth-stimulatory effects of estrogen by inducing glandular and stromal differentiation.[14]This delicate balance is crucial for maintaining normal endometrial health and preventing hyperplasia. In conditions like uterine fibroids, which share genetic origins with endometriosis, estrogen receptor alpha and beta play a role in altered estrogen responsiveness, leading to abnormal cell growth.[18] The interplay between hormonal signals and cellular regulatory networks, including genes like SLC16which are involved in various cellular processes and cancer, contributes to the pathophysiological changes observed in tissues affected by PCOS and its related conditions.[17]
Frequently Asked Questions About Polycystic Ovary Syndrome
Section titled “Frequently Asked Questions About Polycystic Ovary Syndrome”These questions address the most important and specific aspects of polycystic ovary syndrome based on current genetic research.
1. My mom has PCOS; will I definitely get it too?
Section titled “1. My mom has PCOS; will I definitely get it too?”Not necessarily, but your risk is higher. PCOS has a strong genetic component, meaning it often runs in families because multiple genes contribute to susceptibility. However, environmental factors also play a role, so having a family history doesn’t guarantee you’ll develop the syndrome.
2. Why is it so hard for me to lose weight with PCOS?
Section titled “2. Why is it so hard for me to lose weight with PCOS?”Many people with PCOS struggle with weight because of genetic predispositions that influence how your body handles insulin. Insulin resistance, a key feature, leads to higher insulin levels which can stimulate excess androgen production and make weight loss more challenging. Understanding your body’s unique metabolic response is key to managing weight effectively.
3. Why do I have more body hair than my friends?
Section titled “3. Why do I have more body hair than my friends?”This is a common symptom of PCOS called hirsutism, often driven by elevated male hormones (hyperandrogenism) in your body. Genetics can influence how sensitive your hair follicles are to these hormones and how much your ovaries produce. It’s a direct manifestation of the hormonal imbalances associated with the syndrome.
4. Can I still get pregnant easily with PCOS?
Section titled “4. Can I still get pregnant easily with PCOS?”PCOS can make getting pregnant more challenging because it often causes irregular ovulation or anovulation, meaning you don’t release an egg regularly. While genetics contribute to these ovulatory dysfunctions, many women with PCOS successfully conceive with medical management and lifestyle changes. Early diagnosis and treatment are crucial for improving fertility outcomes.
5. Does what I eat really affect my PCOS if it’s genetic?
Section titled “5. Does what I eat really affect my PCOS if it’s genetic?”Absolutely, lifestyle factors like diet significantly interact with your genetic predispositions. While your genes might make you more susceptible to insulin resistance or weight gain, a healthy diet can help manage these symptoms and improve your overall PCOS profile. It’s about workingwith your genetics, not against them.
6. Will I definitely get type 2 diabetes because of my PCOS?
Section titled “6. Will I definitely get type 2 diabetes because of my PCOS?”Having PCOS increases your risk for type 2 diabetes, especially due to the strong link with insulin resistance. However, it’s not a definite outcome. Your genetic background influences this susceptibility, but proactive management through diet, exercise, and sometimes medication can significantly lower your risk and prevent its development.
7. Why do some women with PCOS have worse symptoms than others?
Section titled “7. Why do some women with PCOS have worse symptoms than others?”PCOS is a complex condition, and its severity varies greatly due to the unique combination of genetic variants and environmental factors each person has. The polygenic nature of the disorder means that the specific genes involved and their interactions can lead to a wide range of symptoms and severities.
8. What can a genetic test tell me about my PCOS risk?
Section titled “8. What can a genetic test tell me about my PCOS risk?”Genetic tests could potentially identify specific genetic variants that increase your susceptibility to PCOS or certain symptoms, like insulin resistance. While not routinely used for diagnosis, understanding your genetic profile might help personalize prevention strategies and treatment approaches in the future. Research using genome-wide association studies (GWAS) is continually identifying these risk variants.
9. My sister doesn’t have PCOS, but I do. Why the difference?
Section titled “9. My sister doesn’t have PCOS, but I do. Why the difference?”Even with shared family genetics, individual susceptibility varies because PCOS is polygenic, meaning many different genes and environmental factors contribute. You and your sister might have inherited different combinations of these risk-contributing genes, or experienced different environmental influences that triggered the condition in you but not her.
10. Does my ethnic background influence my PCOS risk?
Section titled “10. Does my ethnic background influence my PCOS risk?”Yes, there can be differences in PCOS prevalence and presentation across various ethnic populations. Genetic variants associated with PCOS can differ, or have varying frequencies, depending on ancestry. This highlights the need for diverse research to understand how different backgrounds might influence risk and symptoms.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
Section titled “References”[1] Hinks, A. “Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis.”Nat Genet, vol. 45, no. 6, 2013, pp. 664-9.
[2] Wolber, LE, et al. “Salt-inducible kinase 3, SIK3, is a new gene associated with hearing.” Hum Mol Genet, vol. 23, no. 24, 2014, pp. 6619-27.
[3] Ishigaki, K. et al. “Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases.” Nat Genet, 2020.
[4] Yang, Q. et al. “Genome-wide association and linkage analyses of hemostatic factors and hematological phenotypes in the Framingham Heart Study.”BMC Med Genet, 2007.
[5] Verbanck, M. et al. “Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases.” Nat. Genet., 2018.
[6] Ripke, S. et al. “Biological insights from 108 schizophrenia-associated genetic loci.”Nature, 2014.
[7] Austin-Zimmerman, I. et al. “Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration.” Nat Commun, 2023.
[8] Wilk, JB. “Framingham Heart Study genome-wide association: results for pulmonary function measures.” BMC Med Genet, vol. 8, S8, 2007.
[9] Wu, X. “A comprehensive genome-wide cross-trait analysis of sexual factors and uterine leiomyoma.” PLoS Genet, 2024.
[10] Choe, E. K., et al. “Leveraging deep phenotyping from health check-up cohort with 10,000 Korean individuals for phenome-wide association study of 136 traits.” Sci Rep, vol. 12, 2022.
[11] McHenry, M. L., et al. “Resistance to TST/IGRA conversion in Uganda: Heritability and Genome-Wide Association Study.” EBioMedicine, vol. 74, 2021.
[12] Tao, F., et al. “Modifier Gene Candidates in Charcot-Marie-Tooth Disease Type 1A: A Case-Only Genome-Wide Association Study.”J Neuromuscul Dis, vol. 6, no. 2, 2019.
[13] Sabatti, C. “Genome-wide association analysis of metabolic traits in a birth cohort from a founder population.”Nat Genet, vol. 41, no. 1, 2009, p. 19060910.
[14] De Vivo, I. et al. “Genome-wide association study of endometrial cancer in E2C2.”Hum Genet, vol. 133, no. 2, 2014, pp. 211-24.
[15] Gallagher, C. S. et al. “Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis.”Nat Commun, vol. 10, no. 1, 2019, p. 4837.
[16] Masuda, T. et al. “GWAS of five gynecologic diseases and cross-trait analysis in Japanese.” Eur J Hum Genet, vol. 27, no. 12, 2019, pp. 1827-33.
[17] Kim, J. et al. “Genome-wide meta-analysis identifies novel risk loci for uterine fibroids within and across multiple ancestry groups.” Nat Commun, vol. 15, no. 1, 2024, p. 1105.
[18] Sliz, E. et al. “Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata.”Nat Commun, vol. 14, no. 1, 2023, p. 574.