Parental Age of Onset of Cardiovascular Disease as a Predictor for Offspring Age of Onset of Cardiovascular Disease

Allport, Shannon A.; Kikah, Ngum; Saif, Nessim Abu; Fonkem, Ekokobe; Atem, Folefac

doi:10.1371/journal.pone.0163334

Cited by 16 publications

(9 citation statements)

References 43 publications

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“…Overall, the RR was 3.79 under the age of 65 and 2.21 over the age of 65; the HR for ischemic stroke was 5.45 under the age of 65 and 2.47 over the age of 65. Additional implicit information from this data, which supports the same conclusion, is listed in Allport et al (2016) The heritability patterns for these diseases are summarized in Table 3. There is qualitative and, increasingly, quantitative knowledge about the progressively declining heritability of these diseases at ages above 50, as well as the decreasing associated familial and GWAS predictive power; see Table 1.…”

Section: Lods With Decreasing Heritability With Agesupporting

confidence: 72%

Age-related late-onset disease heritability patterns and implications for genome-wide association studies

Oliynyk

2018

Preprint

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Background: Genome-wide association studies and other computational biology techniques are gradually discovering the causal gene variants that contribute to late-onset human diseases. After more than a decade of genome-wide association study efforts, these can account for only a fraction of the heritability implied by familial studies, the so-called "missing heritability" problem. Methods:Computer simulations of polygenic late-onset diseases in an aging population have quantified the risk allele frequency decrease at older ages caused by individuals with higher polygenic risk scores becoming ill proportionately earlier. This effect is most prominent for diseases characterized by high cumulative incidence and high heritability, examples of which include Alzheimer's disease, coronary artery disease, cerebral stroke, and type 2 diabetes. Results:The incidence rate for late-onset diseases grows exponentially for decades after early onset ages, guaranteeing that the cohorts used for genomewide association studies overrepresent older individuals with lower polygenic risk scores, whose disease cases are disproportionately due to environmental causes such as old age itself. This mechanism explains the decline in clinical predictive power with age and the lower discovery power of familial studies of heritability and genome-wide association studies. It also explains the relatively constant-with-age heritability found for late-onset diseases of lower prevalence, exemplified by cancers. Conclusions:For late-onset polygenic diseases showing high cumulative incidence together with high initial heritability, rather than using relatively old agematched cohorts, study cohorts combining the youngest possible cases with the oldest possible controls may significantly improve the discovery power of genomewide association studies.Algorithm 1: Sampling individuals diagnosed with a disease proportionately to their polygenic odds ratio and incidence rate. for age = 1 to M axAge do number I ll T hisYear = I(age)· N // N is unaffected population for i = 1 to number I ll T hisYear do HRsum = 0 // will recalculate sum of all HRs for u = 1 to N do HRsum = HRsum + ORt oHR(G u ) // calculate the HR total LOOKU P(add, HRsum, u) // add u th individual to the lookup table r and = RandomN umber(0, HRsum) // pick a random number ill = LOOKU P( f ind, r and, N ) // found newly diagnosed N = N − 1 // decrement in number of healthy individuals P r ocessAndAnal yze(ill) Note: an individual makes a sampling target proportionate to the hazard ratio (HR) in the LOOKU P() table.Odds ratios (ORs) are converted to HRs, similar to the approach taken by . An individual with an HR of 15 will be 150 times more likely to be sampled than an individual with an HR of 0.1. P r ocessAndAnal yze() moves newly diagnosed individual from the healthy to the ill population pool, accounts for allele distribution, case/control ORs, etc.Descriptively, the algorithm works as follows. In this prospective simulation, each next individual to be diagnosed with an LOD is chosen propo...

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Section: Lods With Decreasing Heritability With Agesupporting

confidence: 72%

Age-related late-onset disease heritability patterns and implications for genome-wide association studies

Oliynyk

2018

Preprint

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“…Although the highest cardiovascular risk was associated with a maternal history at age < 50 years and a paternal history at age < 55 years, no substantial differences were seen between maternal and paternal positive CVD history [16]. In a Dutch cohort study, a particularly high incidence of CVD was revealed in people with parental onset of MI before age 70, with maternal history of MI before age 60 being the strongest predictor of CVD incidence [17].The offspring age of onset of CVD is significantly associated with both maternal and paternal age of CVD onset [18]. Nevertheless, data regarding the role of a family history of CVD that includes relatives other than parents or the number of affected family members are scarce.…”

Section: Discussionmentioning

confidence: 96%

Younger age of patients with myocardial infarction is associated with a higher number of relatives with a history of premature atherosclerosis

Ambroziak

Niewczas-Wieprzowska

Maicka

et al. 2020

BMC Cardiovasc Disord

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Background Premature coronary artery disease is one of the most pressing global issues in modern cardiology. The aim of the study was to investigate the role of family history of premature cardiovascular disease (CVD) in patients aged < 50 years with myocardial infarction (MI) compared to that in patients aged ≥50 years with MI and to that in young people without MI (no-MI < 50). Methods The studied group (MI < 50) consisted of 240 patients aged 26–49 years with MI. The control groups consisted of 240 patients (MI ≥ 50) with MI aged 50–92 years and 240 healthy people aged 30–49 years without a history of MI (no-MI < 50). Results There were statistically significant differences between the MI < 50 and MI ≥ 50 and no-MI < 50 groups regarding the family history of premature MI/ischaemic stroke and the percentage of patients with ≥2 relatives affected (10.8, 2.9, and 3.7%, respectively; p < 0.0001). There was a statistically significant difference in the patient age at the first MI occurrence among patients without a family history of premature CVD, those with 1 affected relative, and those with ≥2 affected first-degree relatives (56.6, 48.6 and 41.8 years, respectively) as well as those with affected first- and second-degree relatives (56.5, 50.7 and 47.0 years, respectively). Conclusions A younger age of patients with myocardial infarction is associated with a higher number of relatives with a history of premature MI/ischaemic stroke. Thus, the family history of premature atherosclerosis involving not only first- but also second-degree relatives seems to be a valuable factor in CVD risk evaluation in young people. Graphical Abstract

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“…Although the highest cardiovascular risk was associated with a maternal history at age <50 years and a paternal history at age <55 years, no substantial differences were seen between maternal and paternal positive CVD history [16]. In a Dutch cohort study, a particularly high incidence of CVD was revealed in people with parental onset of MI before age 70, with maternal history of MI before age 60 being the strongest predictor of CVD incidence [17].The offspring age of onset of CVD is signi cantly associated with both maternal and paternal age of CVD onset [18]. Nevertheless, data regarding the role of a family history of CVD that includes relatives other than parents or the number of affected family members are scarce.…”

Section: Discussionmentioning

confidence: 98%

Younger age of patients with myocardial infarction is associated with a higher number of relatives with a history of premature atherosclerosis.

Ambroziak¹,

Niewczas-Wieprzowska²,

Maicka³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background. Premature coronary artery disease is one of the most pressing global issues in modern cardiology. The aim of the study was to investigate the role of family history of premature cardiovascular disease (CVD) in patients aged <50 years with myocardial infarction (MI) compared to that in patients aged ≥50 years with MI and to that in young people without MI (no-MI<50). Methods. The studied group (MI<50) consisted of 240 patients aged 26-49 years with MI. The control groups consisted of 240 patients (MI≥50) with MI aged 50-92 years and 240 healthy people aged 30-49 years without a history of MI (no-MI<50). Results. There were statistically significant differences between the MI<50 and MI≥50 and no-MI<50 groups regarding the family history of premature MI/ischaemic stroke and the percentage of patients with ≥2 relatives affected (10.8%, 2.9%, and 3.7%, respectively; p<0.0001). There was a statistically significant difference in the patient age at the first MI occurrence among patients without a family history of premature CVD, those with 1 affected relative, and those with ≥2 affected first-degree relatives (56.6, 48.6 and 41.8 years, respectively) as well as those with affected first- and second-degree relatives (56.5, 50.7 and 47.0 years, respectively). Conclusions. A younger age of patients with myocardial infarction is associated with a higher number of relatives with a history of premature MI/ischaemic stroke. Thus, the family history of premature atherosclerosis involving not only first- but also second-degree relatives seems to be a valuable factor in CVD risk evaluation in young people.

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Parental Age of Onset of Cardiovascular Disease as a Predictor for Offspring Age of Onset of Cardiovascular Disease

Cited by 16 publications

References 43 publications

Age-related late-onset disease heritability patterns and implications for genome-wide association studies

Age-related late-onset disease heritability patterns and implications for genome-wide association studies

Younger age of patients with myocardial infarction is associated with a higher number of relatives with a history of premature atherosclerosis

Younger age of patients with myocardial infarction is associated with a higher number of relatives with a history of premature atherosclerosis.

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