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Alexander G. Bick
Harvard University
50Publications
19H-index
2,197Citations
Publications 51
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Background: Genetic variation can predispose to disease both through (i) monogenic risk variants in specific genes that disrupt a specific physiologic pathway and have a large effect on disease risk and (ii) polygenic risk that involves large numbers of variants of small effect that affect many different pathways. Few studies have explored the interaction between monogenic risk variants and polygenic risk. Methods: We identified monogenic risk variants and calculated polygenic scores for three d...
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Background: Clonal hematopoiesis of indeterminate potential (CHIP) refers to clonal expansion of hematopoietic stem cells due to acquired leukemic mutations in genes such as DNMT3A or TET2. In huma...
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#1Erik L. Bao (Harvard University)H-Index: 4
#2Satish K Nandakumar (Boston Children's Hospital)H-Index: 1
Last.Vijay G. Sankaran (Boston Children's Hospital)H-Index: 33
view all 33 authors...
Myeloproliferative neoplasms (MPNs) are blood cancers characterized by excessive production of mature myeloid cells that result from the acquisition of somatic driver mutations in hematopoietic stem cells (HSCs). While substantial progress has been made to define the causal somatic mutation profile for MPNs, epidemiologic studies indicate a significant heritable component for the disease that is among the highest known for all cancers. However, only a limited set of genetic risk loci have been i...
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#1Alexander G. Bick (Harvard University)H-Index: 19
#2Joshua S. Weinstock (UM: University of Michigan)H-Index: 1
Last.Sekar Kathiresan (Broad Institute)H-Index: 106
view all 123 authors...
Age is the dominant risk factor for most chronic human diseases; yet the mechanisms by which aging confers this risk are largely unknown. Recently, the age-related acquisition of somatic mutations in regenerating hematopoietic stem cell populations was associated with both hematologic cancer incidence and coronary heart disease prevalence. Somatic mutations with leukemogenic potential may confer selective cellular advantages leading to clonal expansion, a phenomenon termed 9Clonal Hematopoiesis ...
2 CitationsSource
#1Alexander G. Bick (Broad Institute)H-Index: 19
#2E.A. Akwo (VUMC: Vanderbilt University Medical Center)H-Index: 5
Last.Scott M. Damrauer (UPenn: University of Pennsylvania)H-Index: 17
view all 36 authors...
Background: Approximately 13% of black individuals carry 2 copies of the apolipoprotein L1 (APOL1) risk alleles G1 or G2, which are associated with 1.5- to 2.5-fold increased risk of chronic kidney...
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#1James P. Pirruccello (Harvard University)H-Index: 11
#2Alexander G. Bick (Broad Institute)H-Index: 19
Last.Amit Khera (Harvard University)H-Index: 52
view all 13 authors...
Background: Cross-sectional studies of various forms of dilated cardiomyopathy have noted a truncating mutation in the gene encoding titin (9TTNtv9) in 7-30% of patients, but the clinical importance of identifying a TTNtv in an asymptomatic adult is largely unknown. In contrast to cross-sectional studies, prospective cohort studies allow for unbiased estimates of the disease risks associated with a genotype exposure. Objectives: To determine the prevalence of cardiac imaging abnormalities and ri...
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#1Sumeet A. KhetarpalH-Index: 13
#2Arman Qamar (Brigham and Women's Hospital)H-Index: 15
Last.Pradeep NatarajanH-Index: 24
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Highlights •Aging remains the strongest risk factor for ASCVD. •However, the mechanisms underlying how aging and the aging immune system predispose to atherosclerosis remain poorly understood. •CHIP, wherein the hematopoietic stem cell progenitor population clonally expands due to the acquisition of somatic mutations, has implications for ASCVD. •Recent human genetics, epidemiology, and mechanistic investigation in animal models have provided key initial support and hypotheses linking CHIP to AS...
1 CitationsSource
#1Amit KheraH-Index: 52
#2Mark Chaffin (Broad Institute)H-Index: 12
Last.Sekar KathiresanH-Index: 106
view all 19 authors...
Summary Severe obesity is a rapidly growing global health threat. Although often attributed to unhealthy lifestyle choices or environmental factors, obesity is known to be heritable and highly polygenic; the majority of inherited susceptibility is related to the cumulative effect of many common DNA variants. Here we derive and validate a new polygenic predictor comprised of 2.1 million common variants to quantify this susceptibility and test this predictor in more than 300,000 individuals rangin...
27 CitationsSource
#1Connor A. Emdin (Broad Institute)H-Index: 16
#2Mary E. Haas (Broad Institute)H-Index: 10
Last.Sekar Kathiresan (Broad Institute)H-Index: 106
view all 29 authors...
Analyzing 5770 all-cause cirrhosis cases and 572,850 controls from seven cohorts, we identify a missense variant in the Mitochondrial Amidoxime Reducing Component 1 gene (MARC1 p.A165T) that associates with protection from all-cause cirrhosis (OR 0.88, p=2.1*10-8). This same variant also associates with lower levels of hepatic fat on computed tomographic imaging and lower odds of physician-diagnosed fatty liver as well as lower blood levels of alanine transaminase (-0.012 SD, 1.4*10-8), alkaline...
1 CitationsSource
Background: Approximately 13% of African-American individuals carry two copies of the APOL1 risk alleles G1 or G2, which are associated with 1.5-2.5 fold increased risk of chronic kidney disease (C...
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