scholarly journals Association of timing of menarche with depressive symptoms and depression in adolescence: Mendelian randomisation study

2017 ◽  
Vol 210 (1) ◽  
pp. 39-46 ◽  
Author(s):  
Maija-Eliina Sequeira ◽  
Sarah J. Lewis ◽  
Carolina Bonilla ◽  
George Davey Smith ◽  
Carol Joinson
Keyword(s):  
Depressive Symptoms ◽  
Risk Score ◽  
Causal Effect ◽  
Genetic Risk Score ◽  
Mendelian Randomisation ◽  
Age At Menarche ◽  
Genetic Score ◽  
Early Menarche ◽  
Timing Of Menarche ◽  
Effect Of Age

BackgroundObservational studies report associations between early menarche and higher levels of depressive symptoms and depression. However, no studies have investigated whether this association is causal.AimsTo determine whether earlier menarche is a causal risk factor for depressive symptoms and depression in adolescence.MethodThe associations between a genetic score for age at menarche and depressive symptoms at 14, 17 and 19 years, and depression at 18 years, were examined using Mendelian randomisation analysis techniques.ResultsUsing a genetic risk score to indicate earlier timing of menarche, we found that early menarche is associated with higher levels of depressive symptoms at 14 years (odds ratio per risk allele 1.02, 95% CI 1.005–1.04,n=2404). We did not find an association between the early menarche risk score and depressive symptoms or depression after age 14.ConclusionsOur results provide evidence for a causal effect of age at menarche on depressive symptoms at age 14.

scholarly journals Mendelian Randomisation Study of Childhood BMI and Early Menarche

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Hannah S. Mumby ◽  
Cathy E. Elks ◽  
Shengxu Li ◽  
Stephen J. Sharp ◽  
Kay-Tee Khaw ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Instrumental Variable ◽  
Causal Effect ◽  
Absolute Risk ◽  
Mendelian Randomisation ◽  
Age At Menarche ◽  
Causal Association ◽  
Common Variants ◽  
European Descent ◽  
Early Menarche

To infer the causal association between childhood BMI and age at menarche, we performed a mendelian randomisation analysis using twelve established “BMI-increasing” genetic variants as an instrumental variable (IV) for higher BMI. In 8,156 women of European descent from the EPIC-Norfolk cohort, height was measured at age 39–77 years; age at menarche was self-recalled, as was body weight at age 20 years, and BMI at 20 was calculated as a proxy for childhood BMI. DNA was genotyped for twelve BMI-associated common variants (in/nearFTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, ETV5, MTCH2, SEC16B, FAIM2andSH2B1), and for each individual a “BMI-increasing-allele-score” was calculated by summing the number of BMI-increasing alleles across all 12 loci. Using this BMI-increasing-allele-score as an instrumental variable for BMI, each 1 kg/m2increase in childhood BMI was predicted to result in a 6.5% (95% CI: 4.6–8.5%) higher absolute risk of early menarche (before age 12 years). While mendelian randomisation analysis is dependent on a number of assumptions, our findings support a causal effect of BMI on early menarche and suggests that increasing prevalence of childhood obesity will lead to similar trends in the prevalence of early menarche.

Vitamin D-related genes and cardiometabolic markers in healthy children: a Mendelian randomisation study

2020 ◽  
Vol 123 (10) ◽  
pp. 1138-1147
Author(s):  
Ania Lopez-Mayorga ◽  
Hanne Hauger ◽  
Rikke A. Petersen ◽  
Ulla Vogel ◽  
Camilla T. Damsgaard ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vitamin D ◽  
Risk Score ◽  
Cardiometabolic Risk ◽  
Plasma Lipids ◽  
Genetic Risk Score ◽  
Mendelian Randomisation ◽  
Healthy Children ◽  
Genetic Score ◽  
Cardiometabolic Markers

AbstractObservational studies show associations between low serum 25-hydroxyvitamin D (25(OH)D) and cardiometabolic risk markers. This Mendelian randomisation study examined associations between cardiometabolic markers in children and SNP in genes related to vitamin D metabolism (DHCR7; group-specific complement (GC); cytochrome P450 subfamily IIR1 (CYP2R1); and CYP24A1) and action (CYP27B1 and VDR). In 699 healthy 8–11-year-old children, we genotyped eleven SNP. We generated a genetic risk score based on SNP associated with low 25(OH)D and investigated associations between this and blood pressure, plasma lipids and insulin. Furthermore, we examined whether SNP related to vitamin D actions modified associations between 25(OH)D and the cardiometabolic markers. All GC and CYP2R1 SNP influenced serum 25(OH)D. A risk score based on four of the six SNP was associated with 3·4 (95 % CI 2·6, 4·2) mmol/l lower 25(OH)D per risk allele (P < 0·001), but was not associated with the cardiometabolic markers. However, interactions were indicated for the three VDR SNP (Pinteraction < 0·081) on associations between 25(OH)D and TAG, systolic blood pressure and insulin, which all decreased with increasing 25(OH)D only in major allele homozygotes (β –0·02 (95 % CI –0·04, –0·01) mmol/l; β –0·5 (95 % CI –0·9, –0·1) mmHg; and β –0·5 (95 % CI –1·4, 0·3) pmol/l, respectively). In conclusion, genetic variation affected 25(OH)D substantially, but the genetic score was not associated with cardiometabolic markers in children. However, VDR polymorphisms modified associations with vitamin D, which warrants further investigation of VDR's role in the relationship between vitamin D and cardiometabolic risk.

scholarly journals Is a large eye size a risk factor for myopia? A Mendelian randomization study

2017 ◽  
Author(s):  
Keyword(s):  
Risk Factor ◽  
Risk Score ◽  
Refractive Error ◽  
Axial Length ◽  
Genetic Risk ◽  
Causal Effect ◽  
Genetic Risk Score ◽  
Mendelian Randomisation ◽  
Corneal Curvature ◽  
Eye Size

AbstractMyopia (nearsightedness) is an increasingly common cause of irreversible visual impairment. The ocular structures with greatest impact on refractive error are corneal curvature and axial length. Emmetropic eyes range in size within and across species, yet possess a balance between corneal curvature and axial length that is under genetic control. This scaling goes awry in myopia: 1 mm axial elongation is associated with ~3 Dioptres (D) myopia. Evidence that eye size prior to onset is a risk factor for myopia is conflicting. We applied Mendelian randomisation to test for a causal effect of eye size on refractive error. Genetic variants associated with corneal curvature identified in emmetropic eyes (22,180 individuals) were used as instrumental variables and tested for association with refractive error (139,697 individuals). A genetic risk score for the variants was tested for association with corneal curvature and axial length in an independent sample (315 emmetropes). The genetic risk score explained 2.3% (P=0.007) and 2.7% (P=0.002) of the variance in corneal curvature and axial length, respectively, in the independent sample, confirming these variants are predictive of eye size in emmetropes. The estimated causal effect of eye size on refractive error was + 1.41 D (95% CI. 0.65 to 2.16) less myopic refractive error per mm flatter cornea (P<0.001), corresponding to +0.48 D (95% CI. 0.22 to 0.73) more hypermetropic refractive error for an eye with a 1mm longer axial length. These results do not support the hypothesis that a larger eye size is a risk factor for myopia. We conclude the genetic determinants of normal eye size are not shared with those influencing susceptibility to myopia.

scholarly journals Dopamine Genetic Risk Score Predicts Depressive Symptoms in Healthy Adults and Adults with Depression

PLoS ONE ◽  
2014 ◽  
Vol 9 (5) ◽  
pp. e93772 ◽  
Author(s):  
Kristin M. Pearson-Fuhrhop ◽  
Erin C. Dunn ◽  
Sarah Mortero ◽  
William J. Devan ◽  
Guido J. Falcone ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Healthy Adults

scholarly journals Systemic evaluation of the relationship between psoriasis, psoriatic arthritis and osteoporosis: observational and Mendelian randomisation study

2020 ◽  
Vol 79 (11) ◽  
pp. 1460-1467 ◽  
Author(s):  
Jiangwei Xia ◽  
Shu-Yang Xie ◽  
Ke-Qi Liu ◽  
Lin Xu ◽  
Pian-Pian Zhao ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Causal Effect ◽  
Genetic Risk Score ◽  
Final Analysis ◽  
Ultrasound Measurement ◽  
Mendelian Randomisation ◽  
Mineral Density ◽  
Medication Treatment ◽  
Weighted Genetic Risk Score ◽  
The Relationship

Objectives and methodsWith 432 513 samples from UK Biobank dataset, multivariable linear/logistic regression were used to estimate the relationship between psoriasis/psoriatic arthritis (PsA) and estimated bone mineral density (eBMD)/osteoporosis, controlling for potential confounders. Here, confounders were set in three ways: model0 (including age, height, weight, smoking and drinking), model1 (model0 +regular physical activity) and model2 (model1 +medication treatments). The eBMD was derived from heel ultrasound measurement. And 4904 patients with psoriasis and 847 patients with PsA were included in final analysis. Mendelian randomisation (MR) approach was used to evaluate the causal effect between them.ResultsLower eBMD were observed in patients with PsA than in controls in both model0 (β-coefficient=−0.014, p=0.0006) and model1 (β-coefficient=−0.013, p=0.002); however, the association disappeared when conditioning on treatment with methotrexate or ciclosporin (model2) (β-coefficient=−0.005, p=0.28), mediation analysis showed that 63% of the intermediary effect on eBMD was mediated by medication treatment (p<2E-16). Patients with psoriasis without arthritis showed no difference of eBMD compared with controls. Similarly, the significance of higher risk of osteopenia in patients with PsA (OR=1.27, p=0.002 in model0) could be eliminated by conditioning on medication treatment (p=0.244 in model2). Psoriasis without arthritis was not related to osteopenia and osteoporosis. The weighted Genetic Risk Score analysis found that genetically determined psoriasis/PsA were not associated with eBMD (p=0.24 and p=0.88). Finally, MR analysis showed that psoriasis/PsA had no causal effect on eBMD, osteoporosis and fracture.ConclusionsThe effect of PsA on osteoporosis was secondary (eg, medication) but not causal. Under this hypothesis, psoriasis without arthritis was not a risk factor for osteoporosis.

scholarly journals Age at menarche and depression: results from the NHANES 2005–2016

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7150 ◽  
Author(s):  
Yun Shen ◽  
Deepthi S. Varma ◽  
Yi Zheng ◽  
Jenny Boc ◽  
Hui Hu
Keyword(s):  
Depressive Symptoms ◽  
Smoking Status ◽  
Small Sample ◽  
Age At Menarche ◽  
Early Age ◽  
Adult Women ◽  
Early Menarche ◽  
Increased Risk ◽  
Significant Difference ◽  
Adjusted Model

Objective The association between early age at menarche and depression among adolescent girls and adult women has been examined in many studies. However, inconsistent results and limitations such as small sample size, low generalizability, and measurement error exist. We aimed to address these issues to assess the association between age at menarche and depressive symptoms in a nationally representative sample of US women aged 18 years and older. Methods We used the 2005–2016 National Health and Nutrition Examination Survey (NHANES) data with a total of 15,674 women aged 18 years and older included in our study. Logistic regression models were used after adjusting for sociodemographic and health-related factors. Results The crude-adjusted model suggests that women with early age of menarche had 1.36 (95% CI [1.16–1.61]) times the odds of current depressive symptoms compared with the normal menarche group, after controlling for age, race/ethnicity, education, poverty income ratio (PIR) and marital status. In the fully-adjusted model, women with early menarche had 1.25 (95% CI [1.05–1.48]) times the odds of current depressive symptoms, after additionally adjusting for smoking status and body mass index (BMI). However, no significant difference was observed between the normal and late menarche groups. Conclusion Further studies are warranted to determine the causal relationship and mechanisms between early menarche and increased risk of depression.

Abstract 18093: Bleeding Events in Clopidogrel-Treated Patients with STEMI is Associated with a Genetic Risk Score Based on High-Risk Genetic Polymorphisms

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jia-Hui Zhang ◽  
Jin-Qing Yuan ◽  
Xian-Min Meng ◽  
Xiao-Fang Tang ◽  
Jing Wang ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Major Bleeding ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Multivariate Logistic Regression Analysis ◽  
Bleeding Events ◽  
Genetic Score ◽  
Clinical Safety ◽  
Increased Risk

Introduction: Gene polymorphisms of ABCB1, CYP2C19, PON1 and P2Y12 may influence pharmacodynamics and clinical events of clopidogrel treatment. Hypothesis: We assessed the hypothesis that a genetic risk score based on identified high-risk single nucleotide polymorphisms (SNPs) would be associated with bleedings in clopidogrel-treated Chinese STEMI patients after percutaneous coronary intervention (PCI). Methods: A total of 503 consecutive patients with STEMI who received an uneventful PCI and were exposed to clopidogrel treatment for 12 months, were enrolled in the single-center registry. There were 38 tag SNPs selected from ABCB1, CYP2C19, PON1 and P2Y12 genes, which were detected by the ligase detection reaction. The primary clinical safety endpoint was the incidence of major bleeding events. Major bleeding was quantified according to bleeding academic research consortium definition (BARC) criteria, including type 3 and 5 in the analysis. The follow-up period was 12 months. Results: Overall, 46 BARC≥3 bleeding events (9.1%) occurred, which included 11 (2.1%) cases of BARC 3b bleedings and 35 (7.0%) cases of BARC 3a bleedings. After adjustment for traditional clinical risk factors, multivariate logistic regression analysis identified SNPs significantly associated with bleedings were ABCB1 (rs1045642, rs2235047, rs7779562), P2Y12 (rs6809699) and CYP2C19*17. A genetic risk score was constructed by summing the number of risk alleles. Bleedings were significantly associated with increased genetic risk score tertile. Patients in the top tertile of the genetic score were estimated to have a 3.268-fold (95%CI=1.198-8.929, p=0.021) increased risk of bleedings compared with those in the bottom tertile. As a continuous variable, the risk score resulted in an OR of 1.326 per unit increase in score (95%CI=1.098-1.601, p=0.003). Conclusions: This genetic score was significantly associated with bleedings after PCI in our study population.

Will patient’s genetic profile help to choose treatment method of atrial fibrillation?

2019 ◽  
Vol 3 (52) ◽  
pp. 29-30
Author(s):  
Artur Fuglewicz
Keyword(s):  
Atrial Fibrillation ◽  
Single Nucleotide Polymorphisms ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Treatment Method ◽  
Genetic Profile ◽  
Nucleotide Polymorphisms ◽  
Genetic Score ◽  
Single Nucleotide

The paper comments an attempt of genetic score creation of potential atrial fibrillation ablation failure or recurrence AF. This genetic risk score is based on single nucleotide polymorphisms (SNPs) analysis.

scholarly journals Effect of age at puberty on risk of multiple sclerosis

Neurology ◽  
2019 ◽  
Vol 92 (16) ◽  
pp. e1803-e1810 ◽  
Author(s):  
Adil Harroud ◽  
John A. Morris ◽  
Vincenzo Forgetta ◽  
Ruth Mitchell ◽  
George Davey Smith ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Weight Status ◽  
Genome Wide Association Study ◽  
Causal Effect ◽  
Pubertal Timing ◽  
Sensitivity Analyses ◽  
Age At Menarche ◽  
A Genome ◽  
Age At Puberty ◽  
Effect Of Age

ObjectiveTo investigate the potential for a causal effect of age at puberty on multiple sclerosis (MS) susceptibility using a mendelian randomization (MR) approach.MethodsWe used 372 genetic variants strongly associated with age at menarche in a genome-wide association study (GWAS) involving 329,245 women. The genetic architecture of pubertal timing across both sexes is highly correlated (genetic correlation [rg] = 0.75, p = 1.2 × 10−79), allowing these variants to provide reliable insight into pubertal timing in males as well. The effect of pubertal timing on risk of MS was measured with summary statistics from a GWAS of 14,802 cases with MS and 26,703 controls from the International Multiple Sclerosis Genetics Consortium. Multivariable MR controlling for effects of body mass index (BMI) using genetic data from additional consortia investigated whether pubertal effects on MS were dependent on weight status.ResultsA 1-year increase in genetically predicted age at puberty decreased odds of MS by 8% (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.86–0.99, p = 0.03). However, multivariable MR analysis showed that after accounting for effects on adult BMI, the association of age at puberty with MS susceptibility attenuated (OR 0.96, 95% CI 0.88–1.04, p = 0.36). Similar results were obtained when childhood BMI was incorporated. Sensitivity analyses provided no evidence of major bias from genetic pleiotropy.ConclusionsWe found support for an association between higher age at puberty and decreased risk of MS with a magnitude comparable to that reported in observational studies. This effect appears to be largely mediated by the strong association between age at puberty and obesity. A large causal effect of pubertal timing independent of BMI is unlikely.

Early menarche and its relationship to paternal migrant work among middle-school-aged students in China

2019 ◽  
Vol 52 (1) ◽  
pp. 108-116 ◽  
Author(s):  
Bingzheng Zhang ◽  
Ting Yu ◽  
Qiuxing Chen ◽  
Kaye Wellings ◽  
Theresa M. Oniffrey ◽  
...  
Keyword(s):  
Middle School ◽  
Family Relationships ◽  
Paternal Care ◽  
Critical Role ◽  
Age At Menarche ◽  
Early Menarche ◽  
Menarcheal Age ◽  
Migrant Work ◽  
Timing Of Menarche

AbstractAssociations have been shown between father’s absence and menarcheal age, but most studies have focused on absence resulting from divorce, abandonment or death. Little research has been conducted to evaluate the effect on menarcheal age of paternal absence through migrant work. In a sample of 400 middle school students, this study examined the association between paternal migrant work and menarcheal age against a backdrop of extensive rural-to-urban migration in China. Data were collected through a self-reported questionnaire, including social-demographic characteristics, aspects of family relationships, information about father’s migrant work and age at menarche. After adjusting for BMI, parent marital status and perceived relationship with mother, lower self-perceived quality of father–daughter relationship (both ‘father present, relationship poor’ and ‘father absent, relationship poor’) and lower frequency of contact with the father were associated with higher odds for early menarche. These findings suggest that the assumption that father’s absence for work influences the timing of menarche needs to be examined in the context of the quality of the father–daughter relationship and paternal care, which appear to play a critical role in the timing of menarche. These findings also emphasize the importance of enhancing paternal involvement and improving father–daughter relationships in the development of appropriate reproductive strategy in daughters.

Sign in / Sign up

Export Citation Format

Share Document