Michael B Miller
University of Minnesota, Psychology, Department Member
- I study psychology, evolution, genetics, statistics, economics, political science and history of science.edit
Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide... more
Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environment...
Research Interests: Genetics, Intelligence, Bipolar Disorder, Cognition, Computational Biology, and 15 moreBehavior Genetics, Biology, Medicine, Multidisciplinary, Individual Differences, Nature, Brain, Humans, Educational Attainment, Great Britain, Educational Status, Genetic Association, Fetus, Alzheimer Disease, and Gene Expression Regulation
Spontaneous dizygotic (DZ) twinning occurs in 1%-4% of women, with familial clustering and unknown physiological pathways and genetic origin. DZ twinning might index increased fertility and has distinct health implications for mother and... more
Spontaneous dizygotic (DZ) twinning occurs in 1%-4% of women, with familial clustering and unknown physiological pathways and genetic origin. DZ twinning might index increased fertility and has distinct health implications for mother and child. We performed a GWAS in 1,980 mothers of spontaneous DZ twins and 12,953 control subjects. Findings were replicated in a large Icelandic cohort and tested for association across a broad range of fertility traits in women. Two SNPs were identified (rs11031006 near FSHB, p = 1.54 × 10(-9), and rs17293443 in SMAD3, p = 1.57 × 10(-8)) and replicated (p = 3 × 10(-3) and p = 1.44 × 10(-4), respectively). Based on ∼90,000 births in Iceland, the risk of a mother delivering twins increased by 18% for each copy of allele rs11031006-G and 9% for rs17293443-C. A higher polygenic risk score (PRS) for DZ twinning, calculated based on the results of the DZ twinning GWAS, was significantly associated with DZ twinning in Iceland (p = 0.001). A higher PRS was a...
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Postural change in systolic blood pressure (SBP) is prospectively associated with several disease outcomes including hypertension, stroke, and coronary heart disease. The objective of this study was to characterize further a possible... more
Postural change in systolic blood pressure (SBP) is prospectively associated with several disease outcomes including hypertension, stroke, and coronary heart disease. The objective of this study was to characterize further a possible quantitative trait locus on chromosome 18q21 influencing SBP response to a postural challenge. A prior genome scan of postural SBP response in 636 subjects of white ethnicity from 285 hypertensive sibships in the Hypertension Genetic Epidemiology Network (HyperGEN) indicated suggestive evidence for linkage on chromosome 18q21. This study included a de novo set of 452 African American pedigrees from the HyperGEN study and an expanded set of 372 white pedigrees. Variance components linkage analysis of postural SBP change was conducted using microsatellite markers on chromosome 18, and association studies were performed with a common single nucleotide polymorphism (variant 13) in the gene encoding NEDD4L, a key regulator of fine sodium reabsorption in the ...
Research Interests: Genetic Epidemiology, Medicine, Association study, Humans, African American, and 15 moreHypertension, Blood Pressure, Female, Male, American, Clinical Sciences, Aged, Middle Aged, Genotype, Adult, Coronary heart disease, Genetic Polymorphism, Linkage Analysis, Calcium Channel Blocker, and Antihypertensive agents
Antisaccade deficits reflect abnormalities in executive function linked to various disorders including schizophrenia, externalizing psychopathology, and neurological conditions. We examined the genetic bases of antisaccade error in a... more
Antisaccade deficits reflect abnormalities in executive function linked to various disorders including schizophrenia, externalizing psychopathology, and neurological conditions. We examined the genetic bases of antisaccade error in a sample of community-based twins and parents (N = 4,469). Biometric models showed that about half of the variance in the antisaccade response was due to genetic factors and half due to nonshared environmental factors. Molecular genetic analyses supported these results, showing that the heritability accounted for by common molecular genetic variants approximated biometric estimates. Genome-wide analyses revealed several SNPs as well as two genes-B3GNT7 and NCL-on Chromosome 2 associated with antisaccade error. SNPs and genes hypothesized to be associated with antisaccade error based on prior work, although generating some suggestive findings for MIR137, GRM8, and CACNG2, could not be confirmed.
Research Interests: Psychology, Psychophysiology, Adolescent, Medicine, Twins, and 15 moreBiological Sciences, Endophenotypes, Humans, Saccades, Heritability, Aged, Middle Aged, Parents, Adult, Single Nucleotide Polymorphism, Neuropsychological Tests, Molecular Sequence Data, Endophenotype, Psychology and Cognitive Sciences, and Medical and Health Sciences
Available evidence suggests that male homosexuality is both familial and somewhat heritable and that some cases may be caused by an X-linked gene. However, most studies have recruited subjects in a relatively unsystematic manner,... more
Available evidence suggests that male homosexuality is both familial and somewhat heritable and that some cases may be caused by an X-linked gene. However, most studies have recruited subjects in a relatively unsystematic manner, typically via advertisements, and hence suffer from the potential methodological flaw of ascertainment bias due to volunteer self-selection. In the present study we assessed the familiality of male homosexuality using two carefully ascertained samples and attempted to replicate findings consistent with X-linkage in three samples. The percentage of siblings of the probands rated as either homosexual or bisexual, with a high degree of certainty, ranged from 7 to 10% for brothers and 3 to 4% for sisters. These estimates are higher than recent comparable population-based estimates of homosexuality, supporting the importance of familial factors for male homosexuality. Estimates of lambda s for male homosexuality ranged from 3.0 to 4.0. None of the samples showed a significantly greater proportion of maternal than paternal homosexual uncles or homosexual male maternal first cousins. Although our results differed significantly with those of some prior studies, they do not exclude the possibility of moderate X-linkage for male sexual orientation.
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Premorbid risk for major depressive disorder (MDD) and predictors of an earlier onset and recurrent course were examined in two studies in a large, community-based sample of parents and offspring, prospectively assessed from late... more
Premorbid risk for major depressive disorder (MDD) and predictors of an earlier onset and recurrent course were examined in two studies in a large, community-based sample of parents and offspring, prospectively assessed from late childhood into adulthood. In Study 1 (N = 2,764 offspring and their parents), parental psychiatric status, offspring personality at age 11, and age 11 offspring internalizing and externalizing symptoms predicted the subsequent development of MDD, as did poor quality parent–child relationships, poor academic functioning, early pubertal development, and childhood maltreatment by age 11. Parental MDD and adult antisocial behavior, offspring negative emotionality and disconstraint, externalizing symptoms, and childhood maltreatment predicted an earlier onset of MDD, after accounting for course; lower positive emotionality, trait anxiety, and childhood maltreatment predicted recurrent MDD, after accounting for age of onset. In Study 2 (N = 7,146), we examined mo...
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... Disorders Michael B. Miller, J. David Useda, Timothy J. Trull, Rachel M. Burr, and Christa Minks-Brown Introduction ... Michael B. Miller, J. David Useda, Timothy J. Trull, Rachel M. Burr, andChrista Minks-Brown University of... more
... Disorders Michael B. Miller, J. David Useda, Timothy J. Trull, Rachel M. Burr, and Christa Minks-Brown Introduction ... Michael B. Miller, J. David Useda, Timothy J. Trull, Rachel M. Burr, andChrista Minks-Brown University of Missouri-Columbia, Columbia, Missouri 6●●●●. ...
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Background and Purpose— Atherothrombotic diseases, including stroke and myocardial infarction, share a common pathogenesis. Chromosomal regions have been linked to atherothrombotic diseases in family studies, and association studies have... more
Background and Purpose— Atherothrombotic diseases, including stroke and myocardial infarction, share a common pathogenesis. Chromosomal regions have been linked to atherothrombotic diseases in family studies, and association studies have identified candidate gene polymorphisms that affect the risk of stroke and/or myocardial infarction. Using data from the Family Blood Pressure Program, we tested for chromosomal regions linked to the composite phenotype of stroke or myocardial infarction in a large set of hypertensive families. Methods— Nonparametric linkage analysis was implemented in MERLIN, which tests for excess allele-sharing among affected siblings. Empirical distributions based on gene dropping simulations were constructed for each test statistic, and the −log 10 of the associated probability values were compared. Results— Analyses were based on 9607 individuals in 226 black, 395 Hispanic, and 207 white families; 106 families had multiple affected individuals. Several regions...
Research Interests: Genetics, Genomics, Medicine, Association study, Humans, and 15 moreInternal Medicine, Blood Pressure, Female, Male, Clinical Sciences, Aged, Middle Aged, Family Health, Myocardial Infarction, Adult, European Continental Ancestry Group, Family Study, Cerebrovascular Accident, Linkage Analysis, and Cardiovascular medicine and haematology
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Research Interests: Genetics, Human Genetics, Complementary and Alternative Medicine, Biology, Humans, and 15 moreInternal Medicine, African American, Hypertension, Blood Pressure, Female, Individual variation, Aged, Genotype, Linear Regression, Allele, Epidemiologic Studies, angiotensinogen, Genetic factors, Gene frequency, and Antihypertensive agents
Research Interests: Genetics, Human Genetics, Complementary and Alternative Medicine, Family, Biology, and 15 moreCardiovascular disease, Medicine, Humans, Internal Medicine, Blood Pressure, Cholesterol, Female, Alcohol Drinking, Male, Body Mass Index, Genetic linkage analysis, Aged, Human Genome, Adult, and Coronary heart disease
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Research Interests: Endocrinology, Genetics, Biology, Atherosclerosis, Humans, and 15 moreInternal Medicine, Blood Pressure, Cholesterol, Female, Male, Apolipoprotein B, Alcohol Consumption, Clinical Sciences, Aged, Family Health, Genotype, High Density Lipoprotein, Linkage Analysis, Allele Frequency, and Cardiovascular medicine and haematology
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Research Interests: Genetics, Cardiology, Epidemiology, Clinical Trial, Cardiovascular disease, and 15 moreGenetic counseling, Heart Failure, Humans, Hypertension, Female, Insertion, Aged, Genotype, Coronary heart disease, Angiotensin Converting Enzyme, Cardiovascular Events, Antihypertensive agents, High risk, Cardiovascular medicine and haematology, and Cox proportional hazards model
Research Interests: Cardiology, Medicine, Humans, Internal Medicine, Hypertension, and 14 moreFemale, Male, Body Mass Index, African Americans, Middle Aged, Public health systems and services research, Left ventricular hypertrophy, Genetic Polymorphism, European Continental Ancestry Group, Calcineurin, American Heart Association, Base Sequence, systole, and Cardiovascular medicine and haematology
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Research Interests: Psychology, Psychophysiology, Electroencephalography, Adolescent, Medicine, and 15 moreBiological Sciences, Endophenotypes, Brain, Humans, Female, Male, Heritability, Aged, Middle Aged, Genotype, Adult, Genetic Association, Endophenotype, Psychology and Cognitive Sciences, and Medical and Health Sciences
Research Interests: Genetics, Pharmacogenomics, Polymorphism, Clinical Trial, Cardiovascular disease, and 12 moreMedicine, Cardiovascular Risk, Internal Medicine, Gender Difference, Genotype, Coronary heart disease, Allele, Relative Risk, High risk, Pharmacology and pharmaceutical sciences, Doxazosin, and antihypertensive therapy
The utility of genotype imputation in genome-wide association studies is increasing as progressively larger reference panels are improved and expanded through whole-genome sequencing. Developing general guidelines for optimally... more
The utility of genotype imputation in genome-wide association studies is increasing as progressively larger reference panels are improved and expanded through whole-genome sequencing. Developing general guidelines for optimally cost-effective imputation, however, requires evaluation of performance issues that include the relative utility of study-specific compared with general/multipopulation reference panels; genotyping with various array scaffolds; effects of different ethnic backgrounds; and assessment of ranges of allele frequencies. Here we compared the effectiveness of study-specific reference panels to the commonly used 1000 Genomes Project (1000G) reference panels in the isolated Sardinian population and in cohorts of European ancestry including samples from Minnesota (USA). We also examined different combinations of genome-wide and custom arrays for baseline genotypes. In Sardinians, the study-specific reference panel provided better coverage and genotype imputation accurac...
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Research Interests: Psychology, Clinical Psychology, Psychiatry, Psychosis, Psychometrics, and 15 morePsychopathology, Medicine, Humans, Hallucinations, College Students, Risk factors, Rating Scale, Longitudinal Studies, Analysis of Variance, Longitudinal Study, Psychotic Disorders, Risk Factors, Psychiatric Status Rating Scales, Psychology and Cognitive Sciences, and Medical and Health Sciences
Research Interests: Psychology, Abnormal Psychology, Clinical Psychology, Borderline Personality Disorder, Medicine, and 15 moreDisease susceptibility, Humans, Female, Personality Disorder, College Students, Male, Ideation, Interpersonal Relations, Anhedonia, Abnormal, Adult, Control Group, Psychiatric Status Rating Scales, interpersonal relation, and Affective symptoms
Previous analysis in the Hypertension Genetic Epidemiology Network (HyperGEN) of the National Heart Lung and Blood Institute (NHLBI) Family Blood Pressure Program, a multicenter study of genetic and environmental factors related to... more
Previous analysis in the Hypertension Genetic Epidemiology Network (HyperGEN) of the National Heart Lung and Blood Institute (NHLBI) Family Blood Pressure Program, a multicenter study of genetic and environmental factors related to hypertension, indicated regions of linkage for blood pressure traits together with several coincident regions for phenotypically correlated traits, including systolic blood pressure (SBP) response to a postural challenge and body mass index (BMI). Motivated by these findings and by our desire to better understand the physiology of these traits, we conducted bivariate linkage analysis of postural SBP change and BMI. Sibships in HyperGEN were recruited from 5 field centers in Massachusetts, North Carolina, Minnesota, Utah, and Alabama. All available affected siblings, their parents, and selected nonmedicated offspring were recruited. Among 1636 whites and 1747 blacks, we performed a maximum likelihood bivariate genome scan for quantitative trait loci influe...
Research Interests: Genetics, Genetic Epidemiology, Humans, Hypertension, Blood Pressure, and 15 moreFemale, Heritability, Body Mass Index, Clinical Sciences, Aged, Family Health, Genotype, Adult, European Continental Ancestry Group, Body Weight, Genetic Markers, Allele Frequency, alleles, Gene frequency, and Cardiovascular medicine and haematology
Several studies have shown an association between single nucleotide polymorphisms (SNPs) in the angiotensinogen (AGT) gene and hypertension. Because hypertension is a risk factor for left ventricular (LV) hypertrophy and because evidence... more
Several studies have shown an association between single nucleotide polymorphisms (SNPs) in the angiotensinogen (AGT) gene and hypertension. Because hypertension is a risk factor for left ventricular (LV) hypertrophy and because evidence from animal models suggests that AGT may play a role in the growth and hypertrophy of the heart, we chose to conduct a population association study examining the relationship of 10 SNPs in the AGT gene with 7 different LV phenotypes measured by echocardiography. Participants (336 whites and 441 blacks) were drawn from the Hypertension Genetic Epidemiology Network (HyperGEN) study. Individuals were genotyped for 10 previously identified SNPs within the AGT gene. SNP genotype results were regressed against continuous LV phenotypes to test associations separately in each race. Using a cutoff of P <0.005 to account for multiple testing, we found 1 SNP (rs943580) significantly associated with transmitral early peak filling velocity (MVE) in the black ...
Research Interests: Genetics, Genetic Epidemiology, Biology, Echocardiography, Association study, and 15 moreHumans, Hypertension, Haplotypes, Female, Animal Model, Clinical Sciences, Aged, Genotype, Left ventricular hypertrophy, Heart Ventricles, Blood Flow Velocity, Haplotype, angiotensinogen, Left Ventricular, and Cardiovascular medicine and haematology
It remains unclear whether genetic factors contribute to the susceptibility to valve calcification. Accordingly, echocardiograms and genotyping were performed in 1871 hypertensive siblings who participated in the Hypertension Genetic... more
It remains unclear whether genetic factors contribute to the susceptibility to valve calcification. Accordingly, echocardiograms and genotyping were performed in 1871 hypertensive siblings who participated in the Hypertension Genetic Epidemiology Network Study. Genome-wide affected sibpair nonparametric linkage analysis was conducted using the allele-sharing method implemented in the Merlin computer program. A total of 1014 sibships from 858 families were evaluated for aortic valve sclerosis or mitral annular calcification. Of these, 78 sibships from 68 families contained ≥2 affected siblings with ≥1 type of valve calcification (142 affected siblings). All 3 of the traits showed a modest degree of familial aggregation, with sibling recurrence risk (SD) and sibling recurrence risk ratio (95% CI) being 0.25 (0.035) and 2.31 (1.72 to 3.11) for aortic valve sclerosis, 0.25 (0.035) and 1.78 (1.36 to 2.33) for mitral annular calcification, and 0.31 (0.030) and 1.52 (1.24 to 1.85) for aort...
Research Interests: Genetics, Cardiology, Genetic Epidemiology, Biology, Humans, and 15 moreHypertension, Genetic Testing, Bicuspid Aortic Valve, Female, Genetic linkage analysis, Clinical Sciences, Computer Program, Aged, Human Genome, Genotype, Calcinosis, Adult, Aortic Valve, Calcification, and Cardiovascular medicine and haematology
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Background— Previous studies have reported that blood pressure response to antihypertensive medications is influenced by genetic variation in the renin-angiotensin-aldosterone system, but no clinical trails have tested whether the ACE... more
Background— Previous studies have reported that blood pressure response to antihypertensive medications is influenced by genetic variation in the renin-angiotensin-aldosterone system, but no clinical trails have tested whether the ACE insertion/deletion (I/D) polymorphism modifies the association between the type of medication and multiple cardiovascular and renal phenotypes. Methods and Results— We used a double-blind, active-controlled randomized trial of antihypertensive treatment that included hypertensives ≥55 years of age with ≥1 risk factor for cardiovascular disease. ACE I/D genotypes were determined in 37 939 participants randomized to chlorthalidone, amlodipine, lisinopril, or doxazosin treatments and followed up for 4 to 8 years. Primary outcomes included fatal coronary heart disease (CHD) and/or nonfatal myocardial infarction. Secondary outcomes included stroke, all-cause mortality, combined CHD, and combined cardiovascular disease. Fatal and nonfatal CHD occurred in 309...