Study Report

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Basic Info

Reference	Murphy, V. E.,2000 PMID: 11121170
Citation	Murphy, V. E., L. A. Mynett-Johnson, et al. (2000). "Search for bipolar disorder susceptibility loci: the application of a modified genome scan concentrating on gene-rich regions." Am J Med Genet 96(6): 728-732.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	affected sib pairs
Study Type	Genome-wide linkage study
Sample Size	48 families with bipolar disorder, comprising a total of 82 affected sib-pairs.
SNP/Region/Marker Size	65 microsatellite markers throughout the genome, typically every 10 cM
Predominant Ethnicity	Caucasian
Population	Irish

Detail Info

Sample Diagnosis	DSM
Sample Status	The study presented here describes the genotyping of a new collection of 48 Irish families with Inglehearn's panel of markers. These families represent the initial families collected as part of a National Sib-Pair collection and as such each has at least one affected sib-pair grouping.The families, all of Irish origin, were collected as part of a systematic screen of bipolar mood disorder clinics from throughout Ireland by a single clinical team (The Depression Research Unit, St. Patrick's Hospital, Dublin, Ireland). To be included in the National Sib-Pair collection, each family must have a BP I proband plus at least one other sib with a diagnoses of affected under a broad definition (BP I, BP II, schizoaffective disorder [SA], and recurring unipolar depression [RUP]).A total of 205 DNA samples were available for genotyping, of which 130 came from affected individuals (broad affection status: 62% BP I, 23% BP II, 1.5% SA, and 13% RUP), creating a total of 82 (all possible) sib-pairs.
Technique	genotyping
Statistical Method	For each marker, genotypic data were analyzed using Genehunter (Version 1.2) [Kruglyak et al., 1996] to obtain a two-point nonparametric Lod (NPL) score and an associated P value. Heterogeneity Lod scores were also determined using three different genetic models; models I and II assumed autosomal dominant inheritance with low (I) and high (II) age-dependent penetrances, whereas model (III) was autosomal recessive with a high age-dependent penetrance [see Mynett- Johnson et al., 1997 for further details). Two affection models were used for all analyses; a broad model where individuals with BPI, BP II, schizoaffective mix, and recurring unipolar depression were all classed as affected, and a narrow model where only BP I individuals were classed as affected (individuals with other psychiatric diagnoses were classed as unknown).
Result Summary	From the results obtained a number of regions are highlighted for further study. One of these regions (17q11.1-q12) coincides with the location of a candidate gene, the serotonin transporter, whereas others concur with the findings of published studies.

Regions reported by this study for BD (count: 56)

Region	Statistical Values	Author Comments	Result Category
Chr 1	Linkage analysis: broad model, NPL = -0.193, P-value = 0.58; narrow model, NPL = 0.089, P-value = 0.45	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 1_11.25cM	Linkage analysis: broad model, NPL = 0.398, P-value = 0.33; narrow model, NPL = 0.255, P-value = 0.33	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 1_10.29cM	Linkage analysis: broad model, NPL = -0.685, P-value = 0.79; narrow model, NPL = -0.47, P-value = 0.77	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 1_24.5cM	Linkage analysis: broad model, NPL = -0.941, P-value = 0.85; narrow model, NPL = -0.707, P-value = 0.89	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 1_23.88cM	Linkage analysis: broad model, NPL = 0.047, P-value = 0.48; narrow model, NPL = 0.307, P-value = 0.33	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 1_30.42cM	Linkage analysis: broad model, NPL = 0.439, P-value = 0.31; narrow model, NPL = 0.73, P-value = 0.13	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 1_24.7cM	Linkage analysis: broad model, NPL = -0.005, P-value = 0.5; narrow model, NPL = 0.037, P-value = 0.48	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 1_8.34cM	Linkage analysis: broad model, NPL = -0.212, P-value = 0.58; narrow model, NPL = -0.028, P-value = 0.52	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 1_34.44cM	Linkage analysis: broad model, NPL = 0.135, P-value = 0.44; narrow model, NPL = 0.168, P-value = 0.39	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 11	Linkage analysis: broad model, NPL = 0.378, P-value = 0.34; narrow model, NPL = -0.207, P-value = 0.63	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 11_17.08cM	Linkage analysis: broad model, NPL = -1.056, P-value = 0.87; narrow model, NPL = -0.844, P-value = 0.9	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 1_9.05cM	Linkage analysis: broad model, NPL = 1.192, P-value = 0.11; narrow model, NPL = 0.995, P-value = 0.06	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 10	Linkage analysis: broad model, NPL = -0.943, P-value = 0.85; narrow model, NPL = -0.301, P-value = 0.68	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 11_9.08cM	Linkage analysis: broad model, NPL = 0.357, P-value = 0.35; narrow model, NPL = 0.394, P-value = 0.27	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 12	Linkage analysis: broad model, NPL = -0.533, P-value = 0.71; narrow model, NPL = -0.518, P-value = 0.79	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 11_30.97cM	Linkage analysis: broad model, NPL = 0.771, P-value = 0.2; narrow model, NPL = 0.45, P-value = 0.23	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 11_41.21cM	Linkage analysis: broad model, NPL = -0.223, P-value = 0.59; narrow model, NPL = -0.14, P-value = 0.6	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 14	Linkage analysis: broad model, NPL = -0.043, P-value = 0.52; narrow model, NPL = 0.222, P-value = 0.37	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 14_13.36cM	Linkage analysis: broad model, NPL = 1.388, P-value = 0.07; narrow model, NPL = 0.985, P-value = 0.06	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 12_46.2cM	Linkage analysis: broad model, NPL = -1.466, P-value = 0.95; narrow model, NPL = -0.291, P-value = 0.68	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 12_6.65cM	Linkage analysis: broad model, NPL = 0.383, P-value = 0.34; narrow model, NPL = -0.146, P-value = 0.59	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 15_7.43cM	Linkage analysis: broad model, NPL = 0.233, P-value = 0.4; narrow model, NPL = -0.464, P-value = 0.75	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 16	Linkage analysis: broad model, NPL = 1.33, P-value = 0.07; narrow model, NPL = 0.331, P-value = 0.3	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 15	Linkage analysis: broad model, NPL = -0.487, P-value = 0.69; narrow model, NPL = 0.261, P-value = 0.35	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 15_23.52cM	Linkage analysis: broad model, NPL = 0.805, P-value = 0.19; narrow model, NPL = -0.228, P-value = 0.63	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 17_9.14cM	Linkage analysis: broad model, NPL = -0.036, P-value = 0.52; narrow model, NPL = -0.23, P-value = 0.65	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 17_6.97cM	Linkage analysis: broad model, NPL = 1.49, P-value = 0.07; narrow model, NPL = 1.15, P-value = 0.05	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 17_15.71cM	Linkage analysis: broad model, NPL = 0.709, P-value = 0.21; narrow model, NPL = 0.469, P-value = 0.19	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 17	Linkage analysis: broad model, NPL = 1.588, P-value = 0.06; narrow model, NPL = 0.734, P-value = 0.14	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 2_21.45cM	Linkage analysis: broad model, NPL = -0.57, P-value = 0.73; narrow model, NPL = 0.028, P-value = 0.48	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 2	Linkage analysis: broad model, NPL = -0.113, P-value = 0.55; narrow model, NPL = 0.288, P-value = 0.32	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 19_21.88cM	Linkage analysis: broad model, NPL = 0.111, P-value = 0.45; narrow model, NPL = -0.026, P-value = 0.53	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 19	Linkage analysis: broad model, NPL = -0.118, P-value = 0.55; narrow model, NPL = -0.336, P-value = 0.71	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 20_7.68cM	Linkage analysis: broad model, NPL = -1.21, P-value = 0.9; narrow model, NPL = 0.259, P-value = 0.35	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 20	Linkage analysis: broad model, NPL = 0.252, P-value = 0.39; narrow model, NPL = 0.196, P-value = 0.38	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 2_76.9cM	Linkage analysis: broad model, NPL = -1.978, P-value = 0.99; narrow model, NPL = -1.243, P-value = 0.99	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 2_41.26cM	Linkage analysis: broad model, NPL = -1.086, P-value = 0.88; narrow model, NPL = -0.053, P-value = 0.53	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 3_75.99cM	Linkage analysis: broad model, NPL = 0.425, P-value = 0.32; narrow model, NPL = -0.33, P-value = 0.71	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 3	Linkage analysis: broad model, NPL = -0.895, P-value = 0.83; narrow model, NPL = -0.159, P-value = 0.61	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 22_19.62cM	Linkage analysis: broad model, NPL = 0.01, P-value = 0.49; narrow model, NPL = -0.007, P-value = 0.51	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 22	Linkage analysis: broad model, NPL = 0.292, P-value = 0.37; narrow model, NPL = 0.214, P-value = 0.37	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 6	Linkage analysis: broad model, NPL = -0.999, P-value = 0.85; narrow model, NPL = -0.704, P-value = 0.85	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 7	Linkage analysis: broad model, NPL = 0.123, P-value = 0.44; narrow model, NPL = -0.097, P-value = 0.56	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 7_16.83cM	Linkage analysis: broad model, NPL = -0.069, P-value = 0.53; narrow model, NPL = -0.471, P-value = 0.78	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 7_24.6cM	Linkage analysis: broad model, NPL = -0.739, P-value = 0.8; narrow model, NPL = 0.178, P-value = 0.39	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 4	Linkage analysis: broad model, NPL = 0.597, P-value = 0.26; narrow model, NPL = 0.469, P-value = 0.18	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 4_9.13cM	Linkage analysis: broad model, NPL = 0.352, P-value = 0.35; narrow model, NPL = -0.126, P-value = 0.64	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 5	Linkage analysis: broad model, NPL = -0.345, P-value = 0.64; narrow model, NPL = 0.459, P-value = 0.21	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 5_72.48cM	Linkage analysis: broad model, NPL = 1.264, P-value = 0.07; narrow model, NPL = 0.74, P-value = 0.11	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 9_15.75cM	Linkage analysis: broad model, NPL = -0.959, P-value = 0.86; narrow model, NPL = -0.294, P-value = 0.72	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 9_15.7cM	Linkage analysis: broad model, NPL = 1.652, P-value = 0.04; narrow model, NPL = 0.485, P-value = 0.21	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 9_46.76cM	Linkage analysis: broad model, NPL = -1.001, P-value = 0.87; narrow model, NPL = -0.396, P-value = 0.76	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 7_35.83cM	Linkage analysis: broad model, NPL = -0.633, P-value = 0.75; narrow model, NPL = -0.103, P-value = 0.58	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 8	Linkage analysis: broad model, NPL = 0.84, P-value = 0.18; narrow model, NPL = 0.545, P-value = 0.18	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 8_37.49cM	Linkage analysis: broad model, NPL = 0.587, P-value = 0.26; narrow model, NPL = 0.008, P-value = 0.5	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 9	Linkage analysis: broad model, NPL = -0.261, P-value = 0.6; narrow model, NPL = -0.404, P-value = 0.75	No significant linkage was found in this region. No significant linkage was found in this region.	Negative