HARWICK INSTITUTE FOR COGNITIVE RESEARCH BEHAVIORAL GENETICS LABORATORY DIVERGENCE PHENOTYPE STUDY — COHORT SUMMARY Document date: November 2, 1993 Prepared by: M.L. Reyes, Ph.D. Classification: INTERNAL — DO NOT DISTRIBUTE ======================================================================= I. STUDY OVERVIEW ======================================================================= This document summarizes the composition and preliminary findings of the Divergence Phenotype Study cohort as of November 1993. The cohort currently includes forty-seven (47) multi-generational family units representing 183 individual subjects assessed across three generations (G1, G2, G3). Assessment conducted using the Divergence Phenotype Battery (DPB) v.2.1 developed by the principal investigator. See research/div42/ for full assessment battery documentation. Enrollment period: January 1988 – August 1993. Follow-up assessments: ongoing. Funding: Harwick Institute internal grant (BG-88-007), supplemented by an unrestricted gift from an anonymous donor (received 1990). The donor's identity is on file with the Institute director. The principal investigator has not been informed of the donor's identity and has not requested this information. NOTE: The PI raised a concern in July 1993 regarding the anonymous funding arrangement. The concern was noted by the director and the grant was reviewed. The PI was advised that the arrangement is consistent with Institute policy. This note is included for the record. ======================================================================= II. COHORT COMPOSITION ======================================================================= 47 family units / 183 assessed individuals Generation 1 (G1): 47 subjects, mean birth year 1908 (range 1893–1921) Generation 2 (G2): 74 subjects, mean birth year 1934 (range 1919–1952) Generation 3 (G3): 62 subjects, mean birth year 1961 (range 1950–1976) Note: G3 count reflects only subjects who completed full DPB. An additional 19 G3 individuals were identified but declined participation or could not be located (see Section VI). Family units by region of G1 origin: Pacific Northwest (OR, WA): 14 units (29.8%) Northern California: 11 units (23.4%) Intermountain West (CO, UT, NV): 9 units (19.1%) Virginia / Mid-Atlantic: 7 units (14.9%) Other or Unknown: 6 units (12.8%) ======================================================================= III. PHENOTYPE EXPRESSION SUMMARY ======================================================================= High expression (all three DPB criteria strongly present): G1: 31/47 (66%) G2: 28/74 (38%) G3: 41/62 (66%) Moderate expression (two of three criteria): G1: 9/47 (19%) G2: 22/74 (30%) G3: 14/62 (23%) Low or absent expression: G1: 7/47 (15%) G2: 24/74 (32%) G3: 7/62 (11%) OBSERVATION: The elevated G3 expression rate relative to G2 is the primary anomaly of interest in this dataset. In a straightforward dominant-trait model, we would expect G3 rates to approximate G2 rates. They do not. They approximate G1. This is the central finding that prompted the current investigation. See Section IV. Preliminary heritability coefficient: 0.71 (Based on twin comparison and parent-offspring regression; provisional. See: twin_cohort_followup.txt for full twin pair analysis.) ======================================================================= IV. SKIP-GENERATION EXPRESSION PATTERN ======================================================================= In 14 of the 47 family units, the following three-generation pattern was observed and confirmed: G1: HIGH expression G2: LOW or absent expression G3: HIGH expression This pattern — strong expression, suppression, re-expression — is inconsistent with simple Mendelian transmission for dominant traits. Two units showed partial rather than full G2 suppression, which the PI notes may represent incomplete penetrance or an intermediate epigenetic state rather than a departure from the pattern. Family unit codes with confirmed skip-generation pattern: BG-F004, BG-F008, BG-F011, BG-F014, BG-F019, BG-F021, BG-F023, BG-F028, BG-F031, BG-F034, BG-F036, BG-F039, BG-F043, BG-F047 The PI notes that the G1 individuals in these 14 units share a demographic profile discussed in Section V. ======================================================================= V. DEMOGRAPHIC OBSERVATIONS — G1 COHORT ======================================================================= The following is appended at the PI's request. It is flagged as an observation, not a finding, pending further investigation. Of the 47 G1 subjects: — 31 have documented military service, primarily 1928–1945. — Of these 31, 26 served in the United States Army. — Of the 26 Army veterans, 19 were stationed at installations in the Intermountain West or Pacific coast at some point in service. — Complete service records could not be obtained for 8 of these 19 through standard military records requests (NPRC, St. Louis). The PI further notes that the 14 family units with the strongest confirmed skip-generation expression pattern include 13 of the 14 G1 subjects whose service records are incomplete or unavailable. The PI has filed two records requests with the National Personnel Records Center and one direct FOIA request with the Department of Defense. Responses are pending (requests filed: March 1993). This observation is included without conclusion. The sample is small. ======================================================================= VI. NOTES ON RECRUITMENT AND RETENTION DIFFICULTIES ======================================================================= Recruiting and maintaining G3 subject participation has been more difficult than the original study design anticipated. Of 81 G3 individuals identified through G2 contact or family records: — 62 completed the full assessment battery (77%) — 11 formally declined participation — 5 could not be located at last-known addresses (as of Oct 1993) — 3 reported being specifically advised not to participate [source of this advice not disclosed to the PI] The three subjects who reported being advised against participation are noted here without comment. The PI attempted follow-up with two of them. Both declined further contact. The third did not respond. ======================================================================= VII. EDUCATIONAL HISTORY — PRELIMINARY OBSERVATION ======================================================================= An incidental finding during the compilation of G3 family histories warrants further investigation. Preliminary review of G3 educational records (obtained through family contact, not direct institutional request) suggests an elevated rate of participation in specialized enrichment or "gifted" programs among G3 subjects in the 1968–1976 window — specifically among those in the skip-generation expression families. Of the 14 skip-generation G3 subjects with high expression: — 9 have documented participation in a specialized program — Of these 9, records for 4 programs could not be located through standard school district or public records channels The PI notes that this may reflect normal record-keeping gaps for programs of that era. She intends to investigate further. ======================================================================= VIII. NEXT STEPS ======================================================================= 1. Complete G3 follow-up assessments for enrolled cohort. 2. Continue pursuit of G1 military records requests. 3. Investigate G3 educational histories in greater depth. 4. Submit preliminary findings to Journal of Developmental Neuroscience and Behavioral Genetics (target: Q1 1994). 5. Review anonymous donor arrangement with Institute counsel. ======================================================================= Document end. MLR — 02 November 1993