Lazzeroni Biostatistics &
Statistical Genetics Lab
Departments
of Psychiatry & Behavioral Sciences and of Pediatrics
On
this page:
What we do
Who we are
Algorithms and Software
We welcome opportunities for collaboration or consultation.
|
Translational Statistics: We work at the crossroads of statistical science and
contemporary medical and biological research. Our goal is to advance
medical knowledge by engaging as full intellectual partners with colleagues
in Psychiatry, Pediatrics and elsewhere to provide integrated, statistical
solutions to research-generated problems. An important element of our work is the invention and
implementation of new statistical methodology, using high-level computational
skills to translate fundamental concepts, models and principles of statistics
into unique scientific contexts. We are especially interested in
statistical genetics and genomics (including family data); multiple
hypothesis testing and simultaneous inference in complex settings; and
problems that require non-standard statistical models. A notable example can be found in the
seminal paper (below) introducing the Plaid model for identifying two-way
"bi-clusters" in gene expression data. In recent work, we have addressed the
implications of ever-increasing numbers of hypothesis tests in
high-throughput biology and have developed a new, efficient and flexible,
statistical framework for analyzing twin data. |
Laura C. Lazzeroni, PhD (CAP) Associate Professor 650-723-0947 Amrita Ray, PhD Research Associate 650-725-5594 |
The Consortium
on the Genetics of Schizophrenia (COGS; David Braff, Director)
The Department of Veterans Affairs Mental Illness
Research, Education and Clinical Center (VISN 21) (Jerome Yesavage, Director)
The Department
of Veterans Affairs Cooperative Studies Program DNA Bank Coordinating Center
(Ying Lu, Director)
A partial list
of currently funded NIH projects:
·
R01MH086135
(Lazzeroni) 6/6 - The Genetics of Endophenotypes and
Schizophrenia
·
R01DA023063
(Clark) Opioid Efficacy in Humans: A Twin Study
·
R01MH083972
(Hardan) A Neuroimaging Study of Twin Pairs with Autism
·
R01MH073914
(Murphy) Pharmacogenetics of Antidepressant Response
in Geriatric Major Depression
·
RC2HL101748
(O'Brodovich) Genomic Influences on Bronchopulmonary
Dysplasia - A Population-Based Study
·
R01NS070308
(Zhou) Long-term Cognitive Effects of Microembolization
Associated with Carotid Stenting
·
K24MH074467
(Lock) Mentoring and Research in Adolescent Eating Disorders
·
T32MH019938
(Schatzberg) A Biobehavioral Training Program
This
is a partial list of papers by our members. Papers are listed as methods or
applications, however, some or our methods can be found within the
“applied papers” for which they were developed.
Methodological
Papers
Applications in Medicine and Biology
Psychiatry, Pediatrics and
Related Complex Traits
Cancer
Diabetes
Heart Disease
Human Immunodeficiency Virus
(HIV)
Immunology
Liver
Disease
Genomics
Methodological Papers
·
Lazzeroni LC,
Owen A. Plaid models for gene expression
data. Statistica Sinica 12:61-86
·
Lazzeroni LC,
Ray A. The cost of large numbers of
hypothesis tests on power, effect size and sample size.
Molecular Psychiatry Epub ahead of
print
·
Lazzeroni LC,
Lange K. A conditional inference framework
for extending the transmission/disequilibrium test. Human Heredity 48(2):67-81
·
Lazzeroni LC.
Allele sharing and allelic
association: sib pair tests with increased power. Genetic Epidemiology 22(4):328-44
·
Lazzeroni LC.
Linkage disequilibrium and gene
mapping: an empirical least-squares approach. American Journal of Human Genetics
62(1):159-70
·
Lazzeroni LC.
A chronology of fine-scale gene
mapping by linkage disequilibrium. Statistical Methods in Medical Research
10(1):57-76
·
Lazzeroni LC,
Lange K. Markov chains for Monte Carlo tests
of genetic equilibrium. Annals of Statistics 25:136-168
·
Tibshirani R, Lazzeroni
L, Hastie T, Olshen A, Cox C. The global pairwise
approach to radiation hybrid mapping. Stanford
University Division of Biostatistics Technical Report Series No. 201
·
Lazzeroni LC,
Arnheim N, Schmitt K, Lange K. Multipoint mapping calculations for
sperm-typing data. American Journal of Human Genetics 55 (3): 431-6
·
Lazzeroni LC,
Little RJA. Random-effects models for smoothing post-stratification
weights. Journal
of Official Statistics 14:61-78
·
Lazzeroni LC,
Schenker N, Taylor JMG. Robustness of
multiple-imputation techniques to model misspecification. Proceedings of the Survey Research Methods Section, ASA (1990)
260-265
·
Bengtsson H, Ray A,
Spellman P, Speed TP. A single-sample method for normalizing and combining
full-resolution copy numbers from multiple platforms, labs and analysis
methods. Bioinformatics 25(7):861-7
·
Ray A, Weeks
DE. Relationship uncertainty linkage statistics (RULS): affected relative pair
statistics that model relationship uncertainty. Genetic Epidemiology 32(4):313-24
Applications IN MEDICINE AND BIOLOGY
PsychiatrY, Pediatrics and Related Complex Traits
·
Greenwood TA,
Lazzeroni LC, Murray SS, Cadenhead KS, Calkins ME, Dobie DJ, Green MF, Gur RE,
Kelsoe JR, Leonard S, Light GA, Nuechterlein KH, Olincy A, Radant AD, Schork
NJ, Seidman LJ, Siever LJ, Silverman JM, Stone WS, Swerdlow NR, Tsuang DW,
Tsuang MT, Turetsky BI, Freedman R, Braff DL. Analysis of 94 candidate genes and
12 endophenotypes for schizophrenia from the
Consortium on the Genetics of Schizophrenia. American Journal of Psychiatry Epub ahead of
print (doi: 10.1176/appi.ajp.2011.10050723)
·
Selwood SP, Parvathy S, Cordell B, Ryan HS, Oshidari
F, Vincent V, Yesavage J, Lazzeroni LC, Murphy GM. Gene expression profile of the PDAPP
mouse model for Alzheimer's disease with and without Apolipoprotein
E. Neurobiology
of Aging 30(4):574-90.
·
Casper RC,
Gilles AA, Fleisher BE, Baran J, Enns
G, Lazzeroni LC. Length of prenatal exposure to
selective serotonin reuptake inhibitor (SSRI) antidepressants: Effects on neonatal adaptation and
psychomotor development. Psychopharmacology
Epub
ahead of print (doi:10.1007/s00213-011-2270-z)
·
Sarginson JE,
Lazzeroni LC, Ryan HS, Schatzberg AF, Murphy GM. FKBP5 polymorphisms and
antidepressant response in geriatric depression. American Journal of Medical Genetics B,
Neuropsychiatric Genetics 153B(2):554-60.
·
Sarginson JE, Lazzeroni LC, Ryan
HS, Ershoff BD, Schatzberg AF, Murphy GM. ABCB1 MDR1)
polymorphisms and antidepressant response in geriatric depression. Pharmacogenetics and Genomics 20(8):467-75.
·
Sarginson JE,
Killen JD, Lazzeroni LC, Fortmann SP, Ryan HS,
Schatzberg AF, Murphy GM. Markers in the 15q24 Nicotinic
receptor subunit gene cluster (CHRNA5-A3-B4) predict severity of nicotine
addiction and smoking cessation treatment outcomes. American Journal of Medical Genetics B,
Neuropsychiatric Genetics 156(3):275-284.
·
Angst MS,
Phillips NG, Drover DR, Tingle M, Galinkin JL,
Christians U, Swan GE, Lazzeroni LC, Clark JD. Opioid pharmacogenomics
using a twin study paradigm: Methods and procedures for determining familial
aggregation and heritability. Twin Research and Human Genetics 13(5):412-25
·
Taylor JL,
Kennedy Q, Adamson MM, Lazzeroni LC, Noda A, Murphy GM, Yesavage JA. Influences
of APOE e4 and expertise on
performance of older pilots. Psychology
and Aging in press
·
Wroolie TE, Kenna
HA, Williams KE, Powers BN, Holcomb M, Lazzeroni L, Rasgon NL. Cognitive
effects of memantine in postmenopausal women at risk of dementia: a pilot
study. Acta Neurologica Scandinavica. 119 (3):172-9
·
Singh J,
Illes J, Lazzeroni L, Hallmayer J. Trends in US autism research funding. Journal of Autism and Developmental
Disorders 39(5):788-95
·
Hall SS, Lightbody AA, Huffman LC, Lazzeroni LC, Reiss AL. Physiological correlates of social
avoidance behavior in children and adolescents with fragile X syndrome.
Journal of the American Academy of Child
Adolescent Psychiatry 48(3):320-9
·
Traynor J, Agarwal P, Lazzeroni L, Francke
U. Gene expression patterns vary in clonal cell cultures from Rett
syndrome females with eight different MECP2 mutations.
BMC Medical Genetics 3:12
·
Ray A, Weeks
D. No convincing evidence of linkage for restless legs syndrome on chromosoome 9p.
American Journal of Human Genetics
76(4):705-7
·
Casselbrant ML, Mandel EM, Jung
J, Ferrell RE, Tekely K, Szatkiewicz
JP, Ray A, Weeks DE. Otitis media: a genome-wide linkage scan
with evidence of susceptibility loci within the 17q12 and 10q22.3 regions. BMC Medical Genetics 10:85
·
Wu HI, Brown
JA, Dorie MJ, Lazzeroni L, Brown JM. Genome-wide identification of genes
conferring resistance to the anticancer agents cisplatin,
oxaliplatin, and mitomycin
C. Cancer
Research 64(11):3940-8
·
Cancer Genome
Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455(7216):1061-8
·
Hodgson JG, Yeh RF, Ray A, Wang NJ, Smirnov I, Yu M, Hariono S, Silber J, Feiler HS,
Gray JW, Spellman PT, Vandenberg SR, Berger MS, James CD. Comparative analyses
of gene copy number and mRNA expression in glioblastoma
multiforme tumors and xenografts.
Neuro-Oncology 11(5):477-487.
·
Noble JA,
White AM, Lazzeroni LC, Valdes AM, Mirel DB, Reynolds
R, Grupe A, Aud D, Peltz G, Erlich HA. A polymorphism in the TCF7 gene,
C883A, is associated with type 1 diabetes. Diabetes 52(6):1579-82
·
Mirel DB, Valdes AM,
Lazzeroni LC, Reynolds RL, Erlich HA, Noble JA.
Association of IL4R haplotypes with type 1 diabetes. Diabetes 51(11):3336-4
·
Taylor MR, Slavov D, Humphrey K, Zhao L, Cockroft J, Zhu X, Lavori P,
Bristow MR, Mestroni L, Lazzeroni LC. Pharmacogenetic effect of an endothelin-1 haplotype on response to bucindolol
therapy in chronic heart failure. Pharmacogenetics and Genomics. 19(1):35-43
·
Kolek MJ, Carlquist JF, Thaneemit-Chen S,
Lazzeroni LC, Whiting BM, Horne BD, Muhlestein JB,
Lavori P, Anderson JL. The role of a common adenosine monophosphate
deaminase (AMPD)-1 polymorphism in outcomes of
ischemic and nonischemic heart failure. Journal of Cardiac Failure 11(9):677-83
·
Bristow MR,
Murphy GA, Krause-Steinrauf H, Anderson JL, Carlquist JF, Thaneemit-Chen S,
Krishnan V, Abraham WT, Lowes BD, Port JD, Davis GW, Lazzeroni LC, Robertson
AD, Lavori PW, Liggett SB. An {alpha}2C-Adrenergic Receptor Polymorphism Alters
the Norepinephrine Lowering Effects and Therapeutic
Response of the Beta Blocker Bucindolol in Chronic
Heart Failure. Circulation.- Heart
Failure 3(1):21-8.
·
Liggett SB, Mialet-Perez J, Thaneemit-Chen S,
Weber SA, Greene SM, Hodne D, Nelson B, Morrison J, Domanski MJ, Wagoner LE, Abraham WT, Anderson JL, Carlquist JF, Krause-Steinrauf HJ
Lazzeroni LC, Port JD, Lavori PW, Bristow MR. A polymorphism within a conserved
beta(1)-adrenergic receptor motif alters cardiac function and beta-blocker
response in human heart failure. Proceedings
of the National Academy of Science U S A. 103(30):11288-93
·
Sanders GD, Bayoumi AM, Sundaram V, Bilir SP,
Neukermans CP, Rydzak CE,
Douglass LR, Lazzeroni LC, Holodniy M, Owens DK. Cost-effectiveness of screening
for HIV in the era of highly active antiretroviral therapy. New England Journal of Medicine
352(6):570-85
·
Sundaram V,
Lazzeroni LC, Douglass LR, Sanders GD, Tempio P,
Owens DK. A randomized trial of computer-based reminders and audit and feedback
to improve HIV screening in a primary care setting. International Journal of STDs and AIDS 20(8):527-33
·
Owens DK,
Sundaram V, Lazzeroni LC, Douglass LR, Sanders GD, Taylor K, Van Groningen R, Shadle VM, McWhorter VC, Agoncillo
T, Haren N, Nyland J, Tempio P, Khayr W, Dietzen DJ, Jensen P, Simberkoff
MS, Bozzette SA, Holodniy M. Prevalence of HIV infection among
inpatients and outpatients in Department of Veterans Affairs health care
systems: implications for screening programs for HIV.
American Journal of Public Health
97(12):2173-8
·
Owens DK,
Sundaram V, Lazzeroni LC, Douglass LR, Tempio P,
Holodniy M, Sanders GD, Shadle VM, McWhorter VC, Agoncillo T, Haren N, Chavis D, Borowsky LH, Yano EM,
Jensen P, Simberkoff MS, Bozzette
SA. HIV testing of at risk patients in a large integrated health care system. Journal of General Internal Medicine
22(3):315-20
·
Honiden S,
Sundaram V, Nease RF, Holodniy M, Lazzeroni LC, Zolopa A, Owens DK. The effect of diagnosis with HIV
infection on health-related quality of Life. Quality of Life Research (2006) 15 (1):69-82
·
Zolopa AR, Lazzeroni LC, Rinehart A, Vezinet FB, Clavel F, Collier A, Conway B, Gulick
RM, Holodniy M, Perno CF, Shafer RW, Richman DD, Wainberg MA, Kuritzkes DR.
Accuracy, precision, and consistency of expert HIV type 1 genotype
interpretation: an international comparison (The GUESS Study). Clinical Infectious Diseases (2005)
41(1):92-9
·
Lin DY,
Warren JF, Lazzeroni LC, Wolitz RA, Mansour SE. Cytomegalovirus retinitis after
initiation of highly active antiretroviral therapy in HIV infected patients:
natural history and clinical predictors. Retina 22(3):268-77
·
Lech WJ, Wang
G, Yang YL, Chee Y, Dorman K, McCrae D, Lazzeroni LC,
Erickson JW, Sinsheimer JS, Kaplan AH. In vivo
sequence diversity of the protease of human immunodeficiency virus type 1:
presence of protease inhibitor-resistant variants in untreated subjects. Journal of Virology 70(3):2038-43
·
Cao TM,
Lazzeroni LC, Tsai S, Pang WW, Kao A, Camp NJ, Thomas A, Shizuru JA. Identification of a major
susceptibility locus for lethal graft-versus-host disease in MHC-matched mice.
Journal of Immunology 183 (1): 462-9
·
Tsao GJ,
Allen JA, Logronio KA, Lazzeroni LC, Shizuru JA.
Purified hematopoietic stem cell allografts
reconstitute immunity superior to bone marrow. Proceedings of the National Academy of Sciences U S A. 106 (9):
3288-93
·
Bhattacharya
S, Shen-Orr S, Maecker H, Lazzeroni L, Swan GE, Clark
JD, Angst MS, Butte AJ, Davis MM. Immunological response in normal healthy
twins across age. BCB'10 Proceedings of
the First ACM International Conference on Bioinformatics and Computational
Biology
·
Strnad P, Zhou Q, Hanada S, Lazzeroni LC, Zhong BH,
So P, Davern TJ, Lee WM, Acute Liver Failure Group,
Omary MB. Keratin variants predispose to acute liver failure and adverse
outcome: race and ethnic associations. Gastroenterology
139(3):828-35, 835.e1-3
·
Strnad P, Lienau TC, Tao GZ, Lazzeroni LC, Stickel
F, Schuppan D, Omary MB. Keratin variants associate
with progression of fibrosis during chronic hepatitis C infection. Hepatology 43
(6): 1354-63
·
Olivier M, Aggarwal A, Allen J, Almendras
AA, Bajorek ES, Beasley EM, Brady SD, Bushard JM, Bustos VI, Chu A,
Chung TR, De Witte A, Denys ME, Dominguez R, Fang NY, Foster BD, Freudenberg
RW, Hadley D, Hamilton LR, Jeffrey TJ, Kelly L, Lazzeroni L, Levy MR, Lewis SC,
Liu X, Lopez FJ, Louie B, Marquis JP, Martinez RA, Matsuura MK, Misherghi NS, Norton JA, Olshen A, Perkins SM, Perou AJ, Piercy C, Piercy M, Qin F, Reif T, Sheppard
K, Shokoohi V, Smick GA,
Sun WL, Stewart EA, Fernando J, Tejeda, Tran NM,
Trejo T, Vo NT, Yan SC, Zierten DL, Zhao S, Sachidanandam R, Trask BJ, Myers
RM, Cox DR. A high-resolution radiation hybrid
map of the human genome draft sequence. Science 291: 1298-302
·
Beasley EM,
Myers RM, Cox DR, Lazzeroni LC. Statistical refinement of primer
design parameters. In PCR Applications: Protocols for
Functional Genomics. Innis M, Gelfand D, Sninsky J, editors, Academic Press
·
Yu J,
Lazzeroni L, Qin J, Huang MM, Navidi W, Erlich H, Arnheim N. Individual variation in
recombination among human males. American Journal of Human Genetics 59 (6): 1186-92
·
Schmitt K,
Lazzeroni LC, Foote S, Vollrath D, Fisher EM, Goradia TM, Lange K, Page DC, Arnheim
N. Multipoint linkage map of the human pseudoautosomal region, based on single-sperm typing: do
double crossovers occur during male meiosis? American Journal of Human Genetics 55
(3): 423-30
·
Ray A,
Spellman P, Speed TP. Genome-wide associations between SNP genotypes and gene
expression, detected by both frequentist and Bayesian
approaches. JSM Proceedings,
Biometrics Section, American Statistical Association.
Below is a partial list of
novel algorithms and software developed by our members. There are no links yet. Please contact us directly for more
information or to obtain software.
|
PROGRAM |
DESCRIPTION |
WRITTEN IN |
PUBLICATION INTRODUCING THE METHOD |
|
GDF |
Fits
a new generalized Defries-Fulker regression model
for twin data. |
Stata |
Lazzeroni,
Ray. Under review |
|
Cost
of Multiple Tests |
A
user-friendly power, effect size and sample size calculator to compare the
effects of changing different numbers of hypothesis tests or, more
specifically, different genomic platforms. |
Excel |
Lazzeroni,
Ray. Molecular Psychiatry |
|
TST |
Implements
the Total Significance Test for the total number of positive findings among
multiple tests with a complex data structure, based on a sequential step-down
bootstrap algorithm. |
MatLab |
Greenwood,
Lazzeroni ... Braff. American Journal of Psychiatry |
|
TWFIT |
Implements
the Total Significance Test for the total number of positive findings among
multiple tests with a complex data structure, based on a sequential step-down
bootstrap algorithm. |
Stata |
Angst,
... Lazzeroni, Clark. Twin Research and Human Genetics |
|
BOOTCI |
Implements
simultaneous bootstrap confidence intervals for interaction effects. |
MatLab |
Selwood, ...Lazzeroni, Murphy. Neurobiology
of Aging |
|
RANKPERM |
For
quantitative array data and very small samples (e.g. n=6), where it is
impossible for standard permutation tests to reach significance. Performs within-array permutations for
multiple testing of genes that rank consistently high (or low) across samples
or experiments. |
MatLab |
Wu,
... Lazzeroni, Brown. Cancer Research |
|
Plaid |
Fits
the Plaid bi-clustering model, in which rows and columns (genes and samples)
can belong to one, no or more than one cluster, with different ANOVA effects
for each row and column. |
C |
Lazzeroni,
Owen. Statistica Sinica |
|
ESP |
Implements
the Elliptical Sib Pair test, an exact probability test for combined genetic
association and linkage analysis in nuclear families. |
MatLab |
Lazzeroni. Genetic
Epidemiology |
|
ELS |
Fits
the Empirical Least Squares regression model for fine-scale linkage
disequilibrium mapping. |
SPlus |
Lazzeroni. American Journal of Human Genetics |
|
GEN |
Markov
Chain Monte Carlo sampling for large, sparse multidemensional
contingency-tables. Used to test
Hardy-Weinberg and linkage equilibrium on multilocus
genotype data. |
Fortran |
Lazzeroni,
Lange, Annals of Statistics |
|
MCTDT |
Monte
Carlo sampling in parent-child trios to implement the Transmission-Disequilibrium
Test for testing genetic association at multiple loci. |
Fortran |
Lazzeroni,
Lange. Human Heredity |
|
SPERM |
Maximum
likelihood analysis of a hidden Markov model for linkage analysis in sperm
data, accounting for PCR amplification and contamination genotype errors. |
Fortran |
Lazzeroni,
... Lange. American Journal of Human Genetics |
|
RULS |
Relationship
Uncertainty Linkage Statistics in affected relative pairs |
Shell,
R |
Ray,
Weeks. Genetic Epidemiology |
Last update: April 4, 2011
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